The Neuropsychology of Emotion

The Neuropsychology of Emotion
SERIES IN AFFECTIVE SCIENCE

Series Editors
Richard J. Davidson
Paul Ekman
Klaus R. Scherer
THE NATURE OF EMOTION

Fundamental Questions
edited by Paul Ekman and Richard J. Davidson
BOO!
Culture, Experience, and the Startle Reflex
by Ronald Simons
EMOTIONS IN PSYCHOPATHOLOGY
Theory and Research
edited by William F. Hack, Jr., and James D. Laird
WHAT THE FACE REVEALS
Basic and Applied Studies of Spontaneous Expression
Using the Facial Action Coding System (FACS)
edited by Paul Ekman and Erika Rosenberg
SHAME
Interpersonal Behavior, Psychopathology, and Culture
edited by Paul Gilbert and Bernice Andrews
AFFECTIVE NEUROSCIENCE
The Foundations of Human and Animal Emotions
by Jaak Panksepp
EXTREME FEAR, SHYNESS, AND SOCIAL PHOBIA
Origins, Biological Mechanisms, and Clinical Outcomes
edited by Louis A. Schmidt and Jay Schulkin
COGNITIVE NEUROSCIENCE OF EMOTION
edited by Richard D. Lane and Lynn Nadel
ANXIETY, DEPRESSION, AND EMOTION
edited by Richard J. Davidson
PERSONS, SITUATIONS, AND EMOTIONS
An Ecological Approach
edited by Hermann Brandstatter and Andrzej Eliasz
THE NEUROPSYCHOLOGY OF EMOTION
edited by Joan C. Borod
THE
NEUROPSYCHOLOGY
OF
EMOTION
Edited by
Joan C. Borod
OXFORD
UNIVERSITY PRESS
2000
OXFORD
UNIVERSITY PRESS
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Copyright © 2000 by Oxford University Press, Inc.
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All rights reserved. No part of this publication may be reproduced,
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Library of Congress Cataloging-in-Publication Data

The neuropsychology of emotion / edited by Joan C. Borod.
p. ; cm.—(Series in affective science)
Includes bibliographical references.
ISBN 0-19-511464-7
1. Emotions—Physiological aspects.
2. Neuropsychology.
3. Affective disorders—Physiological aspects.
I. Borod, Joan C. n. Series.
[DNLM: 1. Emotions—physiology. 2. Affective Symptoms—psychology.
3. Brain—anatomy & histology. 4. Brain—physiology.
5. Brain—physiopathology. 6. Neuropsychology.
WL 103 N493575 2000] RC455.4.E46 N48 2000 152.4—dc21 99-045300
987654321
Printed in the United States of America
on acid-free paper
To my husband, parents, and sisters
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Preface
During the past few decades, the study of the neural mechanisms that underlie
emotion has blossomed, even though speculations about such mechanisms date
back several centuries. Currently, a wide range of neuroanatomical structures and
neurophysiological systems has been implicated in the phenomenon of emotion.
Furthermore, many theories have emerged from the neuropsychological litera-
ture and from basic emotion research to explain aspects of emotional process-
ing. Evidence for these theories comes from animal and human studies, the lat-
ter involving healthy normal, neurological, and psychiatric populations. In
addition to elucidating brain mechanisms underlying emotional processing, re-
search pertaining to the neuropsychology of emotion has far-reaching implica-
tions for the assessment, diagnosis, treatment, and rehabilitation of individuals
with deficits in emotional processing.
For many years, I had wanted to produce a book about the neuropsychology
of emotion. The controversy surrounding lateralization for emotion was a moti-
vating factor. Although much was known about laterality for cognitive functions,
especially language, hemispheric asymmetries for emotional functioning were
less clear-cut. During the 1980s and early 1990s, I organized several symposia
on the topic at meetings of the International Neuropsychological Society, some
of which led to special journal issues and sections. The first of these issues (Alpert,
Borod, & Welkowitz, 1990) presented experimental studies and discussed theo-
vii
viii PREFACE
retical implications for a range of neuropsychiatric disorders, focusing on two

channels of emotional communication (face and voice). A second endeavor
(Borod, 1993) concerned the processing mode component of emotion and in-
cluded theoretical papers on five different modes: perception, expression, phys-
iology, arousal, and experience. The third contribution (Borod & van Gelder,
1990) had a narrower perspective (i.e., facial asymmetry) and focused on patients
with facial paralysis of both central and peripheral origin.
This book takes a more comprehensive approach to the field. It is unique in
its organization, choice of topics, and focus on theoretical, experimental, and
clinical issues. The book is divided into five sections: (7) Introduction, (2) Back-
ground and General Techniques, (3) Theoretical Perspectives, (4) Emotional Dis-
orders, and (5) Clinical Implications. Part I is an introduction that provides a
brief summary of each chapter and general information about neuropsychologi-
cal parameters of emotion, thus embedding the work in a larger theoretical con-
text. This introductory chapter concludes with suggestions for future research and
clinical work in the field.
Part II of the book provides historical, evolutionary, and philosophical per-
spectives on the neuropsychological study of emotion and information about var-
ious approaches and techniques to study emotion (i.e., neuroanatomical, neuro-
physiological, neuroimaging, and neuropsychological assessment). Moving from
the pragmatic or technical to the more theoretical, Part III presents contempo-
rary theories about emotion, including overviews of those from the basic psy-
chological and neuropsychological literature. In addition, two specific theories
are provided, one from a social-cognitive-neuroscientific perspective and the
other from a neurobiological systems perspective. Included in this section are
discussions about the relationship between emotion and cognitive functions (e.g.,
memory).
The next two sections have a more clinical focus. Part IV features a number
of discrete emotional response systems and emotional disorders, including ela-
tion and mania, sadness and depression, anxiety and stress, anger and impul-
sivity, and flat affect and apathy. Each chapter reviews the neuropsychological
literature pertinent to these discrete systems, drawing on literature from neuro-
logical, psychiatric, and life-span disorders. These chapters include theoretical
discussions about how knowledge of the anatomical and physiological mecha-
nisms underlying these disorders can inform our understanding of the brain mech-
anisms underlying emotion.
Part V focuses directly on clinical implications. In contrast to the previous sec-
tions, this one addresses specific illnesses (i.e., a range of neurological diseases,
depression, and schizophrenia). Here are discussed the emotional deficits ac-
companying these illnesses and specific treatments for these deficits (e.g., psy-
chotherapy, rehabilitation, psychopharmacology, and psychosurgery). The infor-
mation in this section should prove useful to a range of health care professionals
Preface ix
dealing with patient populations suffering from emotional disorders and affec-
tive processing deficits.
This volume contains contributions from some of the most accomplished and
innovative researchers in the field. They were all asked to synthesize the major
work in their area and to provide an overview of the newer studies. In addition,
they were asked to discuss research problems and point out avenues for future
research. The central theme of all the chapters is the question of which neural
mechanisms underlie emotion.
The main aim of this endeavor is to provide a basic textbook and reference
work on emotion for the field of neuropsychology. The volume is designed for
emotion researchers, their students and trainees, and clinicians working with neu-
rological, psychiatric, and geriatric populations. Besides neuropsychologists, this
volume should be useful to colleagues and students in a wide range of related
fields, including clinical and experimental psychology, cognitive neuroscience,
speech and hearing sciences, behavioral neurology, biological psychiatry, neu-
ropsychiatry, gerontology, and rehabilitation medicine.
ACKNOWLEDGMENTS
I am most grateful to Jeffrey House, Vice President at Oxford University Press,

for his invitation to write this book, for his creative and imaginative inspiration
in designing the contents of this book, and for his whole-hearted support and ex-
cellent advice along the way. I am also grateful to Fiona Stevens at Oxford for
her wise guidance and encouragement at the end of this journey.
Second, I want to thank the contributors for their outstanding chapters, their
cheerful enthusiasm (a positive emotion!), and their hard work during the peer
review phase. All chapters were anonymously reviewed by two or three con-
tributors, and each chapter was revised in response to the critiques.
Third, I want to thank Scott Sparks for all his support, hard work on this vol-
ume, sense of aesthetics, and humor over the years. Nancy Wolitzer's input,
assistance, and patience as production editor were invaluable and greatly
appreciated.
Fourth, I would like to thank a number of individuals for their support during this
project: Elissa Koff, Richie Davidson, and Sarah Raskin in the initial stages of this
work; Wendy Heller and Esther Strauss during the middle phase; and Jack Nitschke
and Nancy Madigan at the very end. Also, I am grateful to the students in my re-
search laboratory at Queens College and Mount Sinai Medical Center, who have
listened to tales about this book over the past few years. A special thanks goes to
Matthias Tabert, one of my graduate students, and to Ronald Bloom, my friend and
colleague, for all their help, advice, and moral support throughout and for their re-
spective wisdom about emotion research and clinical work in this area.
X PREFACE
Fifth, I am grateful to my mentors and colleagues who taught me so much

about neuropsychological research and assessment at the Aphasia Research Cen-
ter of the Boston V.A. Hospital: Harold Goodglass, Edith Kaplan, and Nelson
Butters. I am especially grateful to Herbert Caron, who kindled my interest in
facial expression and brain mechanisms in my earlier years at the Cleveland V.A.
Hospital. Justine Sergeant's support of my emotion work over the years has also
been greatly appreciated and is now deeply missed.
Finally, I want to thank my family and friends who have waited patiently for
me to finish this book so that "life as usual" could resume. In this vein, special
acknowledgements go to my dear husband, Paul Kolodner, and my mom, Sylvia
Wise, without whose love, support, and encouragement this work would not have
been possible.
REFERENCES
Alpert, M., Borod, J., & Welkowitz, J. (Eds.) (1990). Faces, voices, and feelings: Exper-
imental techniques and clinical implications [Special Issue]. Journal of Communica-
tion Disorders, 23(4,5).
Borod, J. (Ed.) (1993). Neuropsychological perspectives on components of emotion [Spe-
cial Section]. Neuropsychology, 7, 4.
Borod, J., & van Gelder, R. (Eds.) (1990). Facial asymmetry: Expression and paralysis
[Special Issue]. International Journal of Psychology, 25, 2.
September 1999 J.C.B.

Flushing, New York
Contents
Contributors, xv
Part I Introduction
1. Neuropsychology of Emotion and Emotional Disorders: An Overview
and Research Directions, 3
Joan C. Borod and Nancy K. Madigan
Part II Background and General Techniques

2. The Epistemology of Reason and Affect, 31
Ross W. Buck
3. Anatomy and Physiology of Human Emotion: Vertical Integration
of Brainstem, Limbic, and Cortical Systems, 56
Don M. Tucker, Douglas Derryberry, and Phan Luu
4. Neuropsychological Assessment of Emotional Processing in
Brain-Damaged Patients, 80
Joan C. Borod, Matthias H. Tabert, Cornelia Santschi,
and Esther H. Strauss
xi
xii CONTENTS
5. Neuroimaging Approaches to the Study of Emotion, 106

Mark S. George, Terrence A. Ketter, Tim A. Kimbrell, Andrew M. Speer,
Jeff Lorberbaum, Christopher C. Liberates, Ziad Nahas, and
Robert M. Post
Part III Theoretical Perspectives

6. Psychological Models of Emotion, 137
Klaus R. Scherer
7. A Social Cognitive Neuroscience Approach to Emotion and Memory, 163
Kevin N. Ochsner and Daniel L. Schacter
8. Neurobiology of Emotion at a Systems Level, 194
Ralph Adolphs and Antonio R. Damasio
9. Neuropsychological Theories of Emotion, 214
Guido Gainotti
Part IV Emotional Disorders

10. Elation, Mania, and Mood Disorders: Evidence from
Neurological Disease, 239
Robert G. Robinson and Facundo Manes
11. Regional Brain Function in Sadness and Depression, 269
Richard J. Davidson and Jeffrey Henriques
12. Anxiety, Stress, and Cortical Brain Function, 298
Jack B. Nitschke, Wendy Heller, and Gregory A. Miller
13. Violence Associated with Anger and Impulsivity, 320
Angela Scarpa and Adrian Raine
14. Differentiation of States and Causes of Apathy, 340
Donald T. Stuss, Robert van Reekum, and Kelly J. Murphy
Part V Clinical Implications

15. Neurological Disorders and Emotional Dysfunction, 367
Kenneth M. Heilman, Lee X. Blonder, Dawn Bowers, and
Gregory P. Crucian
Contents x iii
16. Rehabilitation of Emotional Deficits in Neurological Populations:

A Multidisciplinary Perspective, 413
Sarah A. Raskin, Ronald L. Bloom, and Joan C. Borod
17. Emotional Processing in Schizophrenia: A Focus on Affective States, 432
Christian G. Kohler, Ruben C. Gur, and Raquel E. Gur
18. Therapeutic Brain Interventions in Mood Disorders and
the Nature of Emotion, 456
Sarah H. Lisanby and Harold A. Sackeim
Index, 493
Contributors
RALPH ADOLPHS, PH.D. DAWN BOWERS, PH.D.

Department of Neurology Department of Clinical and Health
University of Iowa College of Medicine Psychology
Iowa City, Iowa University of Florida
Gainesville, Florida
LEE X. BLONDER, PH.D.
Department of Behavioral Science Ross W. BUCK, PH.D.
University of Kentucky College Departments of Communication Sciences
of Medicine and Psychology
Lexington, Kentucky University of Connecticut
Storrs, Connecticut
RONALD L. BLOOM, PH.D. GREGORY P. CRUCIAN, PH.D.

Department of Speech-Language-Hearing Department of Neurology
Sciences University of Florida
Hofstra University College of Medicine
Hempstead, New York Gainesville, Florida
JOAN C. BOROD, PH.D. ANTONIO R. DAMASIO, M.D.

Department of Psychology Department of Neurology
Queens College and The Graduate Center University of Iowa College of Medicine
The City University of New York Iowa City, Iowa
Hushing, New York
and RICHARD J. DAVIDSON, PH.D.
Department of Neurology Department of Psychology
Mount Sinai School of Medicine University of Wisconsin
New York, New York Madison, Wisconsin
XV
XVI CONTRIBUTORS
DOUGLAS DERRYBERRY, PH.D. TlM A. KlMBRELL, M.D.

Department of Psychology Biological Psychiatry Branch
Oregon State University National Institute of Mental Health
Corvallis, Oregon Bethesda, Maryland
GUIDO GAINOTTI, M.D. CHRISTIAN G. KOHLER, M.D.

Institute of Neurology Department of Psychiatry
Catholic University of Rome University of Pennsylvania
Rome, Italy Philadelphia, Pennsylvania
MARK S. GEORGE, M.D. CHRISTOPHER C. LIBERATOS, B.S.

Departments of Psychiatry, Radiology,
Departments of Psychiatry, Radiology,
and Neurology
and Neurology
Medical University of South Carolina, and
Medical University of South Carolina
Psychiatric Neuroimaging
Charleston, South Carolina
Ralph H. Johnson V.A. Medical Center
Charleston, South Carolina
SARAH H. LISANBY, M.D.
RAQUEL E. GUR, M.D., PH.D. Department of Biological Psychiatry
Department of Psychiatry New York State Psychiatric Institute
University of Pennsylvania and
Philadelphia, Pennsylvania Department of Psychiatry
Columbia University College of
RUBEN C. GUR, PH.D. Physicians and Surgeons
Department of Psychiatry New York, New York
University of Pennsylvania
Philadelphia, Pennsylvania
JEFF LORBERBAUM, M.D.
KENNETH M. HEILMAN, M.D. Departments of Psychiatry, Radiology,
Department of Neurology and Neurology
University of Florida College of Medicine Medical University of South Carolina
Gainesville, Florida Charleston, South Carolina
WENDY HELLER, PH.D. PHAN Luu, PH.D.

Department of Psychology and Beckman Department of Psychology
Institute for Advanced Science and University of Oregon
Technology and
University of Illinois at Urbana- Electrical Geodesies, Inc.
Champaign Eugene, Oregon
Champaign, Illinois
JEFFREY HENRIQUES, PH.D. NANCY K. MADIGAN, PH.D.

Department of Psychiatry
Department of Psychology
Massachusetts Mental Health Center
University of Wisconsin
Boston, Massachusetts
Madison, Wisconsin
TERRENCE A. KETTER, M.D. FACUNDO MANES, M.D.

Department of Psychiatry Department of Psychiatry
Stanford University University of Iowa College of Medicine
Palo Alto, California Iowa City, Iowa
Contributors XVII
GREGORY A. MILLER, PH.D. HAROLD A. SACKEIM, PH.D.

Departments of Psychology and Department of Biological Psychiatry
Psychiatry and Beckman Institute for New York State Psychiatric Institute
Advanced Science and Technology and
University of Illinois at Urbana-Champaign Department of Psychiatry
Champaign, Illinois Columbia University College of
Physicians and Surgeons
KELLY J. MURPHY, PH.D. New York, New York
Rotman Research Institute
Bay crest Centre for Geriatric Care
University of Toronto CORNELIA SANTSCHI, PH.D.
Toronto, Ontario Institute of Neurology and
Neurosurgery
Canada
Saint Barnabas Medical Center
ZIAD NAHAS, M.D. West Orange, New Jersey
Departments of Psychiatry, Radiology, and
and Neurology Department of Neurology
Medical University of South Carolina New York University School of
Charleston, South Carolina Medicine
New York, New York
JACK B. NrrscHKE, PH.D.
Department of Psychology ANGELA SCARPA, PH.D.
University of Wisconsin Department of Psychology
Madison, Wisconsin Virginia Polytechnic Institute and
State University
KEVIN N. OCHSNER, PH.D. Blacksburg, Virginia
Harvard University
Cambridge, Massachusetts DANIEL L. SCHACTER, PH.D.
ROBERT M. POST, M.D. Harvard University
Biological Psychiatry Branch Cambridge, Massachusetts
National Institute of Mental Health
Bethesda, Maryland
KLAUS R. SCHERER, PH.D.
ADRIAN RAINE, D.PHIL. Department of Psychology
Department of Psychology University of Geneva
University of Southern California Geneva, Switzerland
Los Angeles, California
ANDREW M. SPEER, M.D.
SARAH A. RASKIN, PH.D. Biological Psychiatry Branch
Departments of Psychology and National Institute of Mental Health
Neuroscience Bethesda, Maryland
Trinity College
Hartford, Connecticut
ESTHER H. STRAUSS, PH.D.
ROBERT G. ROBINSON, M.D. Department of Psychology
Department of Psychiatry University of Victoria
University of Iowa College of Medicine Victoria, British Columbia
Iowa City, Iowa Canada
xviii CONTRIBUTORS
DONALD T. STUSS, PH.D. DON M. TUCKER, PH.D.

Rotman Research Institute Department of Psychology
Baycrest Centre for Geriatric Care University of Oregon
and and
Departments of Psychology and Medicine Electrical Geodesies, Inc.
(Neurology and Rehabilitation Eugene, Oregon
Science)
University of Toronto ROBERT VAN REEKUM, M.D.,
Toronto, Ontario F.R.C.P.C.
Canada Kunin-Lunenfeld Applied Research
Unit and Department of Psychiatry
MATTHIAS H. TABERT Baycrest Centre for Geriatric Care
Department of Psychology and
Queens College and The Graduate Center Department of Psychiatry
The City University of New York University of Toronto
Flushing, New York Toronto, Ontario
and Canada
Department of Neurology
Mount Sinai Medical Center
New York, New York
The Neuropsychology of Emotion
I
INTRODUCTION
I
Neuropsychology of Emotion and
Emotional Disorders: An Overview
and Research Directions
JOAN C. BOROD AND NANCY K. MADIGAN
In the past 25 years, the study of neural mechanisms involved in emotional pro-
cessing has flourished, although findings in this area emanate from the end of
the nineteenth century. By emotion, we refer to reactions to an appropriately
evocative stimulus involving cognitive appraisal (or perception), expressive mo-
toric behavior, subjective experience (or feelings), physiological arousal, and
goal-directed behavior (Plutchik, 1984). Researchers have identified numerous
neuroanatomical structures and neurophysiological systems that modulate emo-
tion at cortical, subcortical, and limbic levels of the nervous system. From a neu-
ropsychological perspective, a range of theories has been proposed to account
for cerebral hemispheric specialization of emotion (e.g., right hemisphere, va-
lence, and motoric-direction hypotheses) and for componential and modular pro-
cessing. Evidence for these various theories stems from both clinical observation
and experimental studies, involving normal, neurological, and psychiatric popu-
lations. Experimental studies have employed a variety of methodologies, in-
cluding behavioral paradigms, the natural lesion method, neurosurgical proce-
dures, electrophysiological techniques, and hemodynamic neuroimaging. In
addition to delineating brain mechanisms involved in aspects of emotional pro-
cessing, this growing body of research has wide-ranging clinical implications for
the assessment, diagnosis, treatment, and rehabilitation of neuropsychiatric pop-
ulations suffering from deficits in emotional processing.
3
4 INTRODUCTION
Several critical parameters or factors must be considered in neuropsychologi-

cal studies of emotional processing (see Borod, 1992, 1996; Heilman & Satz,
1983). Two factors are related to brain organization, one being the interhemi-
spheric or laterality factor (right vs. left cerebral hemisphere) and the other be-
ing the intrahemispheric factor, which refers to two different levels of brain
organization—caudality (anterior vs. posterior brain structures) and verticality
(neocortical vs. limbic/subcortical diencephalic regions). The third factor under-
scores the importance of the emotional components themselves by distin-
guishing modes of processing that refer to emotional perception (or comprehen-
sion), expression, physiological arousal, experience, and goal-directed activity
(Plutchik, 1984). Investigators working with neuropsychiatric and normal popu-
lations have studied whether these modes are functionally independent or de-
pendent on one another (Borod, 1993b; Bowers et al., 1993; Gainotti et al., 199
Semenza et al., 1986). The fourth factor is communication channel or the way
in which an emotion is processed. In humans, such modalities typically include
the facial, prosodic/intonational, lexical/verbal, gestural, and postural channels.
Finally, the fifth factor has been the focus of extensive theoretical debate among
emotion theorists (e.g., Ekman & Davidson, 1994; Izard, 1992; Ortony & Turner
1990; Panksepp, 1992) and refers to the examination of basic, discrete emotions
(e.g., happiness, anger, and sadness; Izard, 1977) versus dimensional levels of
emotion, such as emotional valence (pleasantness/unpleasantness) and motoric
direction (approach/withdrawal).
This volume on the neuropsychology of emotion contains sections on back-
ground and general techniques, theoretical perspectives, emotional disorders, and
clinical implications. The current chapter provides an introduction (Part I) that
summarizes each of the chapters in the volume. In addition, directions for future
work in this area are suggested, and research considerations are raised.
BACKGROUND AND GENERAL TECHNIQUES
Part II provides background information about the neuropsychological study of

emotion (Chapters 2 and 3) and information about various approaches to the study
of emotion—neuroanatomical, neurophysiological, neuroimaging, and neu-
ropsychological assessment (Chapters 3-5).
The background information is provided in two chapters elegantly written by
Buck and by Tucker, Derryberry, and Luu. Buck (Chapter 2) provides an epis
temological perspective on the evolution of the conceptualization of emotion and
cognition, based on both the philosophical tradition developed over several cen-
turies and the more recent contributions from neurobiological research. He thus
summarizes the development of relevant philosophical concepts—from mind-
body dualism, to rationalism and empiricism, to pragmatism, to positivism. More-
Neuropsychology of Emotion: An Overview 5
over, Buck reviews the importance and proper use of language in defining such
experiential concepts to describe the mind-brain relationship and how an under-
standing of the neural substrates involved, formalized by LeDoux's research on
fear conditioning (1996), can alter such concepts. He provides definitions for mo-
tivation, emotion, affect, and cognition derived from a historical perspective and
further suggests that these are not distinct but, in fact, interactive phenomena.
For cognition, which is equated with knowledge, he delineates the difference be-
tween "knowledge-by-acquaintance" and "knowledge-by-description." The for-
mer, also termed affective cognition, is self-evident and based on raw perceptual
input from physical, social, and internal body environments, whereas the latter,
termed rational cognition, is representational in nature and reconstructed from
raw perceptual data. A third level of knowledge is one of language competence,
termed understanding. Finally, he proposes that these levels of knowledge may
be associated with specific neural systems in the brain and that, ultimately, an
understanding of emotion may lead to a better understanding of consciousness
itself.
Tucker, Derryberry, and Luu (Chapter 3), arguing from a developmental-
evolutionary perspective, describe the basic neuroanatomy and neurophysiology
of human emotion. The authors describe the subcortical circuits and cortical sys-
tems involved in emotion regulation. They maintain that "these combined de-
scending and ascending influences suggest that emotional states facilitate a ver-
tical integration of processing systems across the brain stem, limbic system, and
cortex" (p. 64). Throughout the chapter, the classic principles of "hierarchic in-
tegration through inhibitory control" (Jackson, 1879) and encephalization are uti-
lized. One of the creative contributions of this chapter is an attempt to delineate
the emotional and motivational functions of the dorsal (the spatial or "where"
pathway) and ventral (the object or "what" pathway) corticolimbic networks.
The next two chapters in Part II provide some basic information about the
techniques used to study emotion: neuropsychological assessment (Chapter 4)
and neuroimaging (Chapter 5). Although many experimental paradigms have
been used to examine emotional processing, some of the more common are lat-
erality techniques (e.g., dichotic listening, tachistoscopic viewing, and facial
asymmetry), the brain lesion method (i.e., studies of individuals with known brain
damage), and electrophysiological and functional brain imaging techniques. Stud-
ies of patients with unilateral brain lesions and normal adult subjects have pro-
vided most of our knowledge base regarding brain-behavior relationships for
components of emotional processing in humans. For laterality studies in normal
individuals, given the typical contralateral innervation of the central nervous sys-
tem, superiority of one side of the body (e.g., left ear, left visual field, or left
hemiface) implies greater involvement of the contralateral cerebral hemisphere
(for reviews, see Borod et al., 1997, 1998a,b; Bruder, 1991; Bryden, 1982; Ley
& Strauss, 1986). Studies with brain-damaged patients, in contrast, examine level
6 INTRODUCTION
of performance on tasks involving emotional processing (for reviews, see Borod,

1993b; Heilman et al., Chapter 15, this volume; Ross, 1997; Starkstein & Robin-
son, 1988). Impaired performance is interpreted as implying that the brain regions
damaged are important for the type of processing involved in that particular task.
Although these methods have identified functional and anatomical substrates in
emotional processing, electrophysiological and functional neuroimaging techniques
(for reviews, see Davidson et al., 1999; Heller & Nitschke, 1998) have provided
way to investigate emotional processing "on line" and in real time, thus affording
a complementary picture of brain-behavior relationships.
Borod, Tabert, Santschi, and Strauss begin Chapter 4 with a comprehensive
review of the literature regarding the neuropsychological assessment of emotional
processing in brain-damaged populations. This chapter offers a unique resource,
as there is a dearth of information about the assessment of emotion in standard
neuropsychological texts and compendia. The chapter is conceptualized via a
componential approach (Borod, 1993a), which has as its basic premise that emo-
tion consists of a number of "components" that utilize different brain systems
(Cripe, 1997). In their review, the authors selected batteries of emotional mea-
sures examining more than one element within a component—a processing mode
(i.e., perception, expression, experience, arousal, or behavior) and/or a commu-
nication channel (i.e., facial, prosodic, lexical, gestural, postural, or scenic [an
environmental/or situational array]). Related studies that include measures of
emotion were integrated into this review. Discussion of the 17 sets of batteries
and studies includes a brief description of each task; the targeted populations;
psychometric properties and normative data, where available; and general re-
search findings. The next part of Chapter 4 contains a summary of information
about eliciting and evaluating emotional expression in neurological populations.
With respect to evaluation, one approach focuses on external expression and the
other on internal states and dispositions. The authors included this summary about
expression due to the complexity of such evaluation and to provide a resource
for researchers and clinicians working in this area.
In Chapter 5, the final chapter of Part II, George and colleagues concisely and
informatively review various neuroimaging approaches and paradigms to the
study of emotion and emotional disorders (e.g., depression). A description of
such techniques and examples of pertinent emotion research are provided for both
structural scanning (i.e., computerized axial tomography [CT] and magnetic res-
onance imaging [MRI]) and functional imaging (i.e., quantitative electroen-
cephalography [EEG], single photon emission computed tomography [SPECT],
positron emission tomography [PET], functional MRI [fMRI], and repetitive
transcranial magnetic stimulation [rTMS]). Throughout Chapter 5, George and
colleagues highlight important theoretical and methodological issues that must
be considered in the design of imaging studies, such as sampling the emotion,
determining/selecting the baseline, designing the statistical analysis, and inter-
preting the results. Interestingly, the authors point out that such studies remind
". . . us of the inextricable links between the mind and the brain . . . [and] offer
the potential of forcing us to change our language about emotion into a more ex-
act, neuroscientifically based discourse" (p. 128).
THEORETICAL PERSPECTIVES
Part III, "Theoretical Perspectives," includes four chapters: Chapter 6, an over-

view of basic psychological theories of emotion (Scherer); Chapter 7, a social-
cognitive-neuroscience perspective (Ochsner & Schacter); Chapter 8, a neurobi-
ological approach from a systems perspective (Adolphs & Damasio); and Chapter
9, a review of theories that are specifically neuropsychological (Gainotti).
Borod's own work in this area has focused on hemispheric specialization for
emotion. The bulk of the research has suggested that emotion is processed pref-
erentially by the right cerebral hemisphere. In a number of review papers (Borod,
1992, 1993a, 1996; Borod, Bloom, & Haywood, 1998a; Borod & Koff, 1989;
see also Tucker, 1981), Borod has speculated on why the right hemisphere may
have come to have a special role in emotion. At a psychological level, emotional
processing involves strategies (e.g., integrative and holistic) and functions (e.g.,
nonverbal and visuospatial) for which the right hemisphere is dominant. Cicone
et al. (1980, p. 155) have suggested that the critical demand of emotional pro-
cessing that engages the right hemisphere is an appreciation of "the 'spatial' or-
ganization among emotions," that is, a "sensitivity to relations among emotions."
At the neurological level, what we know about the right hemisphere is consis-
tent with the strategies and functions associated with emotional processing. In
particular, the right hemisphere, as compared with the left hemisphere, has been
described as having a greater capacity for multimodal integration (Goldberg &
Costa, 1981; Semmes, 1968), greater interlobular organization (Egelko et al.,
1988), more neural interconnectivity among regions (Gur et al., 1980; Thatcher
et al., 1986; Tucker et al., 1986), more widespread stimulus-evoked physiologi-
cal activity (Trotman & Hammond, 1989), and overlapping horizontal axonal
connectivity (Springer & Deutsch, 1989; Woodward, 1988). In sum, these fea-
tures of the right hemisphere may be particularly suited to the multimodal, inte-
grative nature of emotional processing.
Other work, however, has pointed to differential hemispheric specialization as
a function of emotional dimension or emotion type (e.g., Mandal et al., 1999).
A frequently studied dimension of emotion is emotional valence. When lateral-
ity findings emerge, most studies indicate that negative emotional states (e.g.,
disgust) are preferentially processed by the right hemisphere, whereas positive
emotions (e.g., happiness) are subserved by the left hemisphere (for reviews, see
Heller, 1990; Sackeim et al., 1982; Silberman & Weingartner, 1986). A related
8 INTRODUCTION
dimension, motor direction, suggests that withdrawal-related emotions (e.g., fear)

are mediated by the right hemisphere and that approach-related emotions (e.g.,
happiness) are mediated by the left hemisphere (Davidson, 1984; Kinsbourne &
Bemporad, 1984). Hemispheric specialization has been most commonly described
in studies of expression and/or experience, although there are also reports that
involve perception (e.g., Burton & Levy, 1989; Mandal et al., 1999; Moretti e
al., 1996). It has been proposed (Sutton & Davidson, 1997) that dimensions o
valence and motoric direction are overlapping concepts, as most approach emo-
tions are pleasant and most withdrawal emotions are unpleasant (Fox, 1991; Gray
1994; Watson et al., 1999). (Anger, however, is one exception, as it has approach
aspects but is negative in tone [Borod et al., 1981; Davidson, 1993].) Most dat
have implicated frontal and anterior temporal structures in association with these
two dimensions (e.g., Davidson, 1993, 1998). A third dimension that is certainly
integral to emotional processing is arousal. Level of arousal can affect the char-
acterization of the emotional state experienced or expressed. For instance, fear
involves greater arousal than sadness (Mandal, 1986), and joy is more arousing
than contentment (Fredrickson, 1998). In terms of its neural substrates, physio-
logical arousal has been associated with the right cerebral hemisphere, in partic-
ular the posterior parietal region (Eidelberg & Galaburda, 1984; Heilman et al.
1978; Heller, 1993; Heller et al., 1997; Liotti & Tucker, 1992; Tucker &
Williamson, 1984). The chapters to follow not only touch on these models and
distinctions, but go beyond them, as well.
In Chapter 6, Scherer provides an overview of current theoretical models in
the psychology of emotion, tracing the historical roots and noting current con-
troversies in the research that they have generated. Scherer begins with a "mul
ticomponent" definition of emotion that involves the reaction triad (i.e., physio-
logical arousal, motor expression, and subjective feeling), motivational factors
(e.g., action tendencies), and cognitive processes (i.e., evaluation of eliciting
events and regulation of ongoing emotional processes). According to Scherer,
"Emotions are [relatively brief] episodes of coordinated changes in several com-
ponents (including at least neurophysiological activation, motor expression, and
subjective feeling . . .) in response to external or internal events of major sig-
nificance to the organism" (pp. 138-139). For clarity, Scherer includes a table
that contrasts emotions with other affective phenomena (i.e., mood, interpersonal
stances, attitudes, and personality traits). In true definitional fervor, Scherer
makes an appeal for clear delineation of the phenomenon being studied as a pre
requisite to discovering the underlying mechanisms.
Scherer goes on to describe the historical roots of current psychological mod-
els as being built on the thinking of Plato, Descartes, Darwin, and James. The
heart of the chapter describes contemporary models, which Scherer organizes
into four categories: dimensional, discrete emotion, meaning oriented, and com-
ponential. Scherer's own work appears to espouse the componential model, which
is based on "the assumptions that emotions are elicited by a cognitive (but not
necessarily conscious or controlled) evaluation of antecedent situations and events
and that the patterning of the reactions in the different response domains ... is
determined by the outcome of this evaluation process" (p. 149). According to
Scherer, one of the major functions of the componential model is the attempt to
more explicitly connect elicitation circumstances and response patterning.
In Chapter 7, Ochsner and Schacter draw from theory and research in both so-
cial psychology and cognitive neuroscience to provide an informative account of
the relationship between emotion and memory. The authors review the literature,
which is peppered with delightful anecdotes and examples to illustrate their
points. Throughout the chapter, certain cognitive concepts are considered, in-
cluding attention, perception, appraisal, working memory, effort, and reasoning.
The chapter is divided into three main discussions of (1) how emotion guides en-
coding, (2) elaboration and consolidation of information, and (3) retrieval
processes. The chapter also includes important implications for mental health
practitioners (e.g., the value of placing a positive spin on stressful life events)
and offers useful suggestions for future research vis-a-vis normal aging and
neuroimaging.
In Chapter 8, Adolphs and Damasio present a neurobiological systems-level
theory of emotion motivated by evolutionary and ecological mechanisms and fo-
cused on "knowledge about emotion." Critical to their definition of emotion is
the idea that emotions engage neural structures that represent body states and
that link perception of external stimuli to body states (Damasio, 1994, 1995).
The heart of the chapter is a description of the role of the amygdala in a variety
of activities—social judgments, recognition of emotional facial expressions, aver-
sive fear conditioning, and learning and emotional development (see also
LeDoux, 1996). Both human and animal experimental data are reviewed, and il-
lustrative case materials are provided. The authors review the neuroanatomical
projections of the amygdala, a collection of nuclei located in the anterior mesial
temporal lobe, which receives highly processed information about all modalities.
A system of numerous reciprocal connections from somatosensory cortices with
many other brain structures (e.g., ventromedial frontal cortex, basal ganglia, thal-
amus, hippocampus, and basal forebrain) and projections to the hypothalamus
defines the anatomical amygdala. According to Adolphs and Damasio, "the amyg-
dala is situated so as to link information about external stimuli conveyed by sen-
sory cortices . . . with modulation of decision-making, memory, attention, and
somatic, visceral, and endocrine processes" (p. 197). They further point out that
all of these processes are influenced by the emotional significance of the exter-
nal stimulus.
Adolphs and Damasio turn next to the role of right-hemisphere somatosensory
cortices in processing emotion, focusing on the parietal cortex. They postulate
why emotions should be lateralized and specifically to the right hemisphere, with
10 INTRODUCTION
an emphasis on the processing of somatic information and body states. The chap-
ter is closed with the suggestion that future research focus on the neural systems
involved in the sociocultural aspects of emotion and in the social emotions (e.g.,
jealousy, pride, and embarrassment; Ross et al., 1994). The authors conclude that
"ultimately . . . , emotions . . . will be seen to arise from relations between
multiple brains and their external environments, embedded in the context of
a particular culture" (p. 209), which well portrays their evolutionary and eco-
logical perspective.
Part III ends with Chapter 9, by Gainotti, on neuropsychological theories of
emotion, which the author describes as "the set of theoretical models that have
accompanied and oriented clinical and experimental studies aiming to clarify the
relationships between emotions and the brain" (p. 214). Chapter 9 gives equal
consideration to psychological models of emotion and to neurological mecha-
nisms. According to Gainotti, these theories have been influenced by (7) the rep-
resentation and organization of emotions in the human brain (i.e., emotional di-
mensions vs. discrete emotional categories) and (2) the componential nature of
emotions, that is, whether there is a "central processor" of emotions or whether
emotional components are subserved by different parts of the brain (see also
Borod, 1993b). The initial discussion in Chapter 9 reviews studies pertaining to
the historical development of neuropsychological theories in terms of subcorti-
cal/limbic mechanisms and hemispheric asymmetries.
The second half of Gainotti's chapter describes current neuropsychological
theories of emotion with a stronger focus on human than on animal research and
with an attempt to take into account the range of neural structures that have been
studied. In developing a viable neuropsychology theory, Gainotti contends that
the following issues need to be considered: (7) the relationship between emo-
tional and cognitive systems, (2) the features distinguishing the emotional from
the cognitive system (see Table 9.1), (3) the componential nature of emotions,
and (4) the hierarchical organization of the emotional processing system. Gain-
otti makes a compelling argument for integrated, rather than independent, emo-
tional and cognitive systems. He points out that the general architectures of the
two systems are similar, whereas their scopes are quite different. The emotional
system is viewed as an emergency one with the ability to rapidly and automati-
cally process stimuli and trigger a response. In contrast, the cognitive system is
both a more advanced and a more complex system with the ability to analyze
information through the selection of appropriate strategies (see also Oatley &
Johnson-Laird, 1987). When discussing the hierarchical nature of emotional pro-
cessing, Gainotti suggests that the two sides of the brain may play complemen-
tary roles in emotional behavior, with the right hemisphere more involved in the
automatic, spontaneous, and schematic aspects of emotion and the left hemi-
sphere more instrumental in controlling and modulating emotion (Buck, 1984).
He concludes with a discussion of the possible relationships between left/right
Neuropsychology of Emotion: An Overview II
and cortical/subcortical distinctions. A case is made for both "top-down" (i.e.,

left-hemisphere cortical dominance for cognitive and control functions) and
"bottom-up" (i.e., greater emotional involvement of right-hemisphere subcorti-
cal structures [e.g., the amygdala]) processing.
EMOTIONAL DISORDERS
Part IV, "Emotional Disorders," features a spectrum of basic emotional response

systems: elation and mania; sadness and depression; anxiety and stress; violence,
anger, and impulsivity; and apathy (i.e., the absence of emotion). The authors in
this part describe the neurological, psychiatric, and/or life-span disorders asso-
ciated with each response system and review the neuropsychological literature
pertinent to each discrete emotional system. In addition, the authors provide the-
oretical discussions about how knowledge of the neuroanatomical, physiologi-
cal, and biochemical substrata underlying these disorders can inform our under-
standing of brain-behavior relationships for emotion.
Chapter 10 is by Robinson and Manes. It reflects their perspective on elation,
mania, and mood disorders after two decades of work focused on the emotional,
cognitive, and behavioral changes associated with focal brain injury. They point
out that there have been largely two perspectives in investigations of this nature:
"One attributes mood disorders to an understandable psychological reaction to
the associated impairment; the other, based on a lack of association between
severity of impairment and severity of emotional disorder, suggests a direct causal
connection between emotional disorders and structural brain damage" (p. 240).
The authors begin with an elegant history of a century of work in this area, fo-
cusing largely on case descriptions that primarily involve cerebrovascular dis-
ease. The authors then review the following emotional changes and associated
disorders: mania in stroke, mania in traumatic brain injury, depression in stroke,
depression in Parkinson's disease, and depression in traumatic brain injury. In
each case, the authors comment on a variety of factors, including lesion location,
neural mechanisms, prevalence, risk factors, and longitudinal course. In terms of
brain-behavior relationships, the authors suggest that mania is most frequently
associated with right-hemisphere cortical lesions, bipolar disorder with right-
hemisphere subcortical lesions, and depression with left-hemisphere cortical
(frontal) and subcortical (basal ganglia) lesions. Finally, specific treatments are
discussed for each disorder and disease. Although the focus of treatment is on
psychopharmacology, suggestions for future research into treatment focus on so-
cial intervention.
In Chapter 11, Davidson and Henriques provide an excellent review of the
brain mechanisms underlying sadness and depression, drawing largely from the
normal adult literature, but also from studies of neurological and psychiatric dis-
12 INTRODUCTION
orders, using electroencephalography, event-related potential, and blood flow

procedures. In addition to pointing out various critical methodological is-
sues throughout, the authors provide a theoretical backdrop regarding the
approach/withdrawal laterality model (Davidson, 1984) and its relationship to pos-
itive/negative affective expression and experience and to anterior brain activation
asymmetries (Davidson, 1984, 1998). According to Davidson and Henriques, "ab-
solute anterior asymmetry by itself does not produce a particular pattern of emo-
tional behavior or psychopathology; instead anterior asymmetry is seen as a diathe-
sis (or constitutional predisposition) for the expression of emotional behavior, given
an appropriate affect elicitor" (p. 270). From the emotion perspective, Davidson
maintains that sadness and depression should be associated with reduced left frontal
activation, reflecting decreased positive affect. Specifically, individuals who have
a characteristic pattern of left frontal hypoactivation should be more susceptible to
sad mood induction and should have an increased risk for depression. Importantly,
the authors explain that sadness and depression are not the same; sadness is viewed
as only one aspect of depression, which also includes loss of pleasure, loss of in-
terest, and social withdrawal. In fact, at the end of Chapter 11, they raise the in-
teresting question of "whether sadness in normal people is a good model system
for clinical depression" (p. 287).
In Chapter 12, Nitschke, Heller, and Miller continue the focus on negative
emotional states, examining anxiety and stress. In addition, the authors consider
the role of stress in anxiety. They review evidence linking different types of anx-
iety to specific patterns of regional brain function and discuss the implications
of these connections in terms of cognition. The major premise on which Chap-
ter 12 is based is that there are two types of anxiety: "anxious apprehension"
(AAP), characterized by concern and worry about the future, muscle tension, and
verbal rumination about negative expectations and fears; and "anxious arousal"
(AAR), associated with panic, feelings of fear, and pounding heart and triggered
by threats representing an immediate danger. Conceptually, this distinction dif-
fers from the classic distinction between trait and state anxiety. Central to the re-
lationship between these types of anxiety and brain function is the concept of
stress, with the authors attending to the important distinction between external
stressors and psychological stress.
In terms of brain asymmetry, the authors hypothesize that AAP (in right-handed
people) would more likely be associated with increased left-hemisphere activity
due to the major verbal component integral to worry and cognitive rumination,
whereas AAR would be linked to increased right-hemisphere posterior activity,
as there is literature (e.g., Heller, 1993; Heller et al., 1997) linking somatic arousal
to posterior regions of the right hemisphere. According to Heller (1993, pp.
480-481), the properties of the right hemisphere, and especially the tem-
poroparietal region, "encompass the cognitive, attentional, and physiological at-
tributes that would be useful for optimal efficiency in responding to environ-
mental events." In support of their hypotheses, the authors provide compelling

and consistent evidence from studies cutting across technique domains (i.e., elec-
trophysiological, hemodynamic, behavioral, neurological, psychiatric, and cog-
nitive). An important point made by the authors pertains to the comorbidity be-
tween anxiety and depression. The authors point out that, although greater right
than left anterior cortical activity has been found in both AAR and depression,
increased right posterior activity is unique to AAR, whereas reduced left ante-
rior activity and reduced right posterior activity are unique to depression.
Scarpa and Raine, in Chapter 13, also invoke a dichotomous distinction as the
framework for understanding brain-behavior relationships for violence, anger,
and impulsivity. Paralleling the categories of defensive and predatory behavior
in animals, human aggression has been categorized as "impulsive-emotional" or
"controlled-instrumental" (Vitiello & Stoff, 1997). Impulsive aggression occurs
suddenly in reaction to threat or provocation within the context of increased anger,
emotionality, and impulsivity; it is reactive, affective, and defensive. Controlled
aggression, on the other hand, manifests itself as a relatively nonemotional dis-
play of aggression directed at obtaining some goal; it is proactive, manipulative,
and predatory. From Chapter 13, it appears that the neuropsychology of impul-
sive-emotional aggression is the better understood of the two. Impulsive aggres-
sion is ascribed to greater right-hemisphere activation, especially in frontotem-
poral regions and connections to limbic and hypothalamic structures, which in
turn are important in the expression and regulation of emotion.
The evidence reviewed about these two forms of aggression, with a particular
focus on the impulsive type of aggression, are from studies involving neuropsy-
chological testing, neurological disorders (e.g., temporal lobe epilepsy), neu-
roimaging, neurochemistry, hormonal levels, and psychophysiology (i.e., skin
conductance, heart rate, EEG activity, and ERP). Typically, low levels of auto-
nomic activity appear to be related to antisocial behavior and nonviolent crimes,
whereas increased autonomic reactivity is related to the impulsive-emotional
form of aggression. Scarpa and Raine explain that psychophysiological reactiv-
ity is related to aggression in the context of increased negative affect and thought
processes. Reminiscent of theorizing by Davidson and Henriques (Chapter 11,
this volume). Chapter 13 concludes with the point that biological predispositions
and cognitive deficits interact with adverse social and environmental factors to
produce impulsive-emotional behavior.
Chapter 14, the final one in this part, examines apathy, whose dictionary defi-
nitions are the "absence of emotion" and the "lack of interest or concern," thus
representing an endpoint on the spectrum of emotional disorders. The objectives
of the authors (Stuss, van Reekum, & Murphy) are to revisit historical concepts
and definitions, to review the evidence from the neuropsychiatric literature, and
to creatively determine their own neuropsychologically relevant definition of ap-
athy. The definition of apathy arrived at by Stuss, van Reekum, and Murphy is
14 INTRODUCTION
"an absence of responsiveness to stimuli as demonstrated by a lack of self-initi-

ated action" (p. 342). According to the authors, there are many advantages to this
definition: (7) it provides for objective behavioral measurement, (2) it is neither a
single state nor a syndrome, and (3) it can be divided into different states (or types)
that are separable in terms of both the psychological mechanisms and the neural
substrates involved. Their definition is intrinsically flexible, because, by using an
adjectival descriptor that denotes the major qualities of the kind of apathetic be-
havior referred to, both increased scope and increased specificity are permitted.
In the course of Chapter 14, the authors provide a unique review of the causes
of and disorders associated with apathy disturbances, including localized brain dys-
function (e.g., frontal lobes, basal ganglia, thalamus, and medial forebrain bundles),
dementia (e.g., frontal lobe dementia, Huntington's disease, and Alzheimer's dis-
ease), and psychiatric disorders (e.g., depression and negative-symptom schizo-
phrenia). From their review of the literature, the authors conclude that neurologi-
cally based apathy typically involves frontal/subcortical or frontolimbic system
circuity. The review is followed by a thoughtful discussion of the authors' con-
ceptualization of apathy states in relation to disturbances of arousal and to other
theoretical perspectives. The chapter ends with a description of treatment inter-
ventions that involve pharmacotherapy (e.g., via increasing dopaminergic activity)
and behavioral rehabilitation (e.g., social skills training). The authors conclude that
treatment for apathy will be most effective when the underlying psychological and
pathophysiological mechanisms are clearly understood (e.g., Stuss, 1987).
CLINICAL IMPLICATIONS
The final section of the book, Part V, focuses on clinical implications. In con-
trast to Part IV, where a discrete emotional response system or an emotional dis-
order was emphasized, in Part V a specific illness (i.e., neurological disease, de-
pression, and schizophrenia) is the focus. In addition, information is provided
regarding specific treatments for the various disorders, including rehabilita-
tion, psychotherapy, and brain interventions (e.g., pharmacotherapy and psy-
chosurgery). In general, the chapters are filled with theoretical ideas and con-
ceptualizations that provide yet another route to unravel the nature of emotion
vis-a-vis neuroanatomical and neurophysiological mechanisms. The information
in Part V should be useful to health care professionals dealing with patient pop-
ulations suffering from emotional disorders and affective processing deficits.
The section begins with Chapter 15, by Heilman, Blonder, Bowers, and Cru-
cian, who discuss how various neurological diseases impact on emotional expe-
rience, mood, and the communication of emotion (i.e., comprehension and ex-
pression). The brain structures that figure prominently in Chapter 15 are the
posterior neocortex, basal ganglia, portions of the limbic system, and frontal
lobes. The chapter begins with an excellent review of the literature that describes
emotion deficits associated with each disorder and discusses underlying neural
mechanisms. The following brain regions and respective diseases are included:
cortical dysfunction (e.g., left-hemisphere damage, right-hemisphere damage, and
corticobulbar dysfunction), limbic system dysfunction (e.g., amygdalectomy, en-
cephalitis, and complex partial seizures), and basal ganglia diseases (e.g., Parkin-
son's disease, Huntington's disease, progressive supranuclear palsy, Wilson's dis-
ease, striatonigral degeneration, and Sydenham's chorea).
Heilman and colleagues then describe possible mechanisms that link concepts,
theories, and neural substrates. In terms of emotional communication disorders,
concepts involving iconic representation, motoric representation, and innate
cross-cultural mechanisms are discussed. In terms of emotional experience and
mood disorders, the discussion of mechanisms focuses on feedback theories
(i.e., facial, visceral, and autonomic nervous system) and CNS theories (i.e.,
subcortical/diencephalic and modular). They also acknowledge the major con-
tribution of neocortical mechanisms, maintaining that "there is overwhelming ev-
idence that in humans the neocortex is critical for interpreting the meaning of
many stimuli that induce an emotional experience" (p. 391).
The authors focus mostly on modular theories that postulate, according to the au-
thors, dedicated centers and systems for each emotion or nondevoted systems me-
diating more than one emotion or specific emotional dimension. According to Heil-
man (1997), the conscious experience of emotion is mediated by "anatomically
distributed modular networks;" these modules determine valence, control arousal,
and mediate motor activation (approach vs. avoidance). The chapter provides an ex-
cellent critique of the valence dimension. For the arousal dimension, the authors
present a discussion about the specific neural mechanisms underlying attention, stim-
ulus novelty and significance, and asymmetric control of physiological arousal. In
their discussion of the "motor activation" dimension, the authors maintain that the
right hemisphere has a special role in motor activation and intention. In their con-
clusion, the authors summarize their theory on the neural mechanisms underlying
emotional experience, behavior, and communication.
In Chapter 16, Raskin, Bloom, and Borod discuss rehabilitation of a range of
emotional deficits, with a focus on neurological disorders. In keeping with the
spirit of the volume, a multidisciplinary approach is taken. The authors begin by
describing various approaches to rehabilitation, including cognitive remediation,
speech-language therapy, multidisciplinary and milieu treatment, and caregiver
participation programs. In addition, they describe the assessment and evaluative
techniques that accompany rehabilitation and discuss the important principle of
treatment generalization.
The chapter's main focus is on the treatment of the emotional deficits that fol-
low neurological disorders and acquired brain injury. Recent work has indicated
that affective difficulties in such populations are directly amenable to remedia-
16 INTRODUCTION
tion techniques (e.g., Myers, 1998; Tompkins, 1995), although they have rarely
been attempted to date. As a prelude to this part of the chapter, a brief overview
is provided regarding some of the emotional deficits associated with common
neurological disorders (i.e., traumatic brain injury, stroke, Parkinson's disease,
Alzheimer's disease, and multiple sclerosis). Then, specific treatment approaches
are described (e.g., cognitive remediation, behavioral therapies, and relaxation
training) for depression, anxiety, post-traumatic stress disorder, anger, apathy and
indifference, and affective deficits that reflect channel-specific or mode-specific
impairments. Chapter 16 concludes with the suggestion that the componential
approach to emotional processing described by Borod (1993b), which is similar
to the modular theories described by Heilman et al. (Chapter 15, this volume)
and the componential perspective provided by Gainotti (Chapter 9, this volume),
provides both a potential way to organize and to evaluate the treatment of emo-
tional deficits from a neuropsychological perspective.
This section on clinical implications moves from neurological diseases and
brain injury to two chapters on psychiatric disorders. Kohler, Gur, and Gur, in
Chapter 17, examine affective processes in schizophrenia, with a focus on mood
disorders. They review the schizophrenia literature from a particular conceptual
perspective, broadly covering the literature, as well as highlighting their own re-
search pertinent to the topic. The chapter begins with an informative historical
review of the development of the concept and symptoms of schizophrenia. The
authors then describe affective processes in schizophrenia from the perspective
of deficits in emotional expression (e.g., flat affect), emotional experience (e.g.,
depression), and emotion recognition (e.g., face perception). As a follow-up to
this description of deficits, the authors discuss psychopharmacological treatments
for aspects of schizophrenia, including psychotic symptoms, depression, schizoaf-
fective disorder, and negative symptoms (i.e., flat affect, alogia, and anhedonia).
Chapter 17 concludes with an explanation of how neurobiological studies (i.e.,
brain metabolism and blood flow) have advanced the understanding of emotion-
related symptoms in schizophrenia. The authors make three interesting points in
this regard. First, in their own work (Kohler et al., 1998), schizophrenics with
depression had larger temporal lobe volumes. According to the authors, "the as-
sociation of depression with normal temporal lobe volumes . . . suggests that
some integrity of the temporal lobe is necessary for the experience of depres-
sion, consistent with evidence for the role of the temporal lobe in emotional ex-
perience" (p. 446). Second, depression in schizophrenia is associated with a rel-
ative decrease in left compared with right anterior cingulate activity, consistent
with lesion studies pointing to greater right hemisphere involvement in negative
emotional states (e.g., Gainotti, 1972; Sackeim et al., 1982). Third, because of
altered metabolic functioning in frontal regions, the authors conclude that "the
neurobiology of depression in schizophrenia has features in common with major
depression and depression associated with other brain disorders" (p. 447).
The final chapter, Chapter 18, deals directly with mood disorders (i.e., de-
pression and mania) in psychiatric populations. The authors, Lisanby and Sack-
eim, present a comprehensive state-of-the-art review of somatic interventions for
these disorders, including psychopharmacological agents, electroconvulsive ther-
apy (ECT), functional neurosurgery, and repetitive transcranial magnetic stimu-
lation (rTMS). According to Lisanby and Sackeim, these four different treatments
have "mood-altering effects but differ in their mechanisms of action and degree
of anatomical specificity" (p. 456). Besides providing a wealth of material about
treatment, the authors summarize the knowledge gained during treatment of mood
disorders about the neurobiological theories regarding the nature and regulation
of emotion.
One of the considerations that emerges from the discussion of psychophar-
macology pertains to whether there is a direct relationship between the mecha-
nisms that regulate mood alterations (i.e., sadness and happiness) in healthy nor-
mal subjects and those that underlie the psychiatric disorders of major depression
and mania. From the evidence reviewed, the authors suggest that the studies in
normal individuals may be of limited relevance to the psychiatric studies, and
vice versa. Moreover, they suggest that normal people and depressed people may
have different neural representations of emotion. One of the promising new spec-
ulations emerging from the ECT research is that bilateral frontal ECT may be
more effective than the more traditional frontotemporal placement and its asso-
ciated amnestic effects. In their discussion of psychosurgery, the authors provide
an excellent history and review of the procedures utilized to treat psychiatric dis-
orders over the years, including leukotomy, thalamotomy, cingulotomy, subcau-
date tractotomy, and limbic leukotomy. In general, the work in this area supports
the role of limbic structures in mood regulation.
The authors conclude their chapter with a description of an exciting new
technique (i.e., rTMS) that provides a noninvasive method of direct cortical
stimulation as we move into the new millenium. The initial studies reviewed
here have implications for contemporary theories regarding hemispheric spe-
cialization for emotion as a function of valence. Preliminary studies (e.g.,
George et al., 1996) suggest that rTMS of the dorsolateral prefrontal cortex
on the left side leads to transient dysphoria and on the right side leads to mood
elevation.1 Clinically, however, there is some suggestion of therapeutic effects
in depression with left-sided stimulation and in mania with right-sided stim-
ulation. Yet again, the findings implicate paradoxical effects in normal ver-
sus psychiatric populations.
l
In a similar vein, Borod et al. (2000) found a "reversed valence" effect in a study of verbal prag-
matic aspects of discourse production in individuals with unilateral stroke. Right-hemisphere dam-
age was associated with impairment in positive emotion and left-hemisphere damage with impair-
ment in negative emotion.
18 INTRODUCTION
FUTURE DIRECTIONS AND RESEARCH CONSIDERATIONS
We want here to highlight some of the questions raised in this volume, discuss
several related areas of emotion research, and suggest possible directions for fur-
ther exploration of emotional processing in neuropsychological investigations.
Perhaps the most perplexing question of brain-behavior relationships is why
it has been so difficult to delineate the specific neural substrates involved in emo-
tional processing. Intricate brain-behavior models have been proposed in other
areas of neural functioning, such as the visual system (Livingstone & Hubel,
1988; Ungerleider & Mishkin, 1982). In part, this is because visual stimuli per
se lend themselves to concrete and discernible parameters, such as form, color,
movement, and depth perception, variables that are easily tested in animal mod-
els. In the current volume, Buck (Chapter 2, this volume) notes the importance
of defining the components being examined in emotion research and how such
definitions may be altered once the underlying neural organization is understood.
Explicit definitions are crucial to furthering our knowledge of how the brain
processes emotion (e.g., Scherer, Chapter 6, this volume).
Many of the working definitions for describing components of emotional pro-
cessing are, however, quite broad, as are the brain regions that have often been
implicated. Perhaps this is due to the limitations of the currently available tech-
nology for studying human emotional functioning, but, as has been suggested
(e.g., Heilman et al., Chapter 15, this volume), it also might reflect very wide-
spread neural substrates underlying these processes. Functional neuroimaging and
lesion method studies have clarified the specific brain substrates involved to a
degree, but much more work is needed to understand the interplay between such
substrates and processing modes.
A recent example of such an attempt is Mayberg's model of depression (1997),
which delineates potential neural pathways and altered relationships among var-
ious brain regions. Another example, along these lines, is the associative mem-
ory, object-based processing subserved by the amygdala (see Adolphs & Dama-
sio, Chapter 8, this volume), investigations of which in humans have been based
on models developed from animal studies (e.g., LeDoux, 1992, 1993). Offering
theoretical models is an important step (e.g., Davidson & Henriques, Chapter 11;
Gainotti, Chapter 9; Nitschke, Heller, & Miller, Chapter 12; and Scherer, Chap-
ter 6, this volume), but the challenge is to develop rigorous tests of these pro-
posals. In other areas, models are awaiting development, such as the interface
between emotion and memory (e.g., Hamann et al., 1999; LeDoux, 1996; Os-
chsner & Schacter, Chapter 7, this volume), as well as the interaction between
emotion and other aspects of cognition (e.g., attention; LeDoux, 1996).
Most authors in this volume emphasize the need for clear and concise defini-
tions of emotional parameters in order to design experiments that can further our
knowledge regarding the brain substrates implicated by clinical neuropsycho-
logical and functional neuroimaging studies. This includes the importance of sub-
typing clinical disorders based on specific symptoms, not only to enhance our
understanding of the neural substrates of emotion but also to refine treatment in-
terventions. Such subtyping, which is essential in emotion research, has emerged
and is reviewed in this volume for anxiety (Nitschke, Heller, & Miller, Chapter
12), schizophrenia (Kohler, Gur, & Gur, Chapter 17), aggression (Scarpa & Raine,
Chapter 13), and apathy (Stuss, van Reekum, & Murphy, Chapter 14). For ex-
ample, many functional neuroimaging studies indicate altered frontal brain asym-
metry in depression, yet the contributing factors (e.g., affective, motivational, or
cognitive) remain enigmatic. Categorizing individuals with symptoms predomi-
nantly representing one type, dimension, or factor may provide further clarifica-
tion. Moreover, subtyping individuals within a particular disorder may eventu-
ally lead to a better understanding of the genetic components involved in certain
disease states and how genetic vulnerabilities (i.e., risk factors) interact with en-
vironmental or neurological (i.e., brain insult) stressors to result in pathological
states.
The issue and need for subtyping individuals parallels the issue concerning in-
dividual differences (or subject characteristics) in emotional processing. The pri-
mary characteristics studied to date are age and gender. In terms of affective
changes with age, most studies have focused on psychopathology and emotional
experience. For example, most studies have reported an increase in depression
with age, whereas most have not found any significant age-related changes in
emotional experience per se (for review, see Grunwald et al., 1999). For emo-
tional expression, studies examining posed facial expressions have found older
participants to be less accurate than younger participants (Levenson et al., 1991;
Malatesta & Izard, 1984; Yecker et al., 2000). In contrast, investigations of spon-
taneous expression have found either no age-related changes as a function of age
(Levenson et al., 1991; Malatesta et al., 1987) or greater expressivity in older
adults (Malatesta et al., 1992).
In terms of gender, several investigations indicate that women are better de-
coders of emotional stimuli than men (e.g., Brody, 1985; Duda & Brown, 1985;
Grunwald et al., 1999; Hall, 1978; LaFrance & Banaji, 1992; Otta et al., 1996;
Shields, 1991) and that women are more emotionally expressive than men (e.g.,
Ashmore, 1990; Brody & Hall, 1993). The findings regarding differences in emo-
tional experience between men and women are, however, equivocal, with some
studies finding that women report experiencing emotion more intensely than men
(Choti et al., 1987; Grunwald et al., 1999; Gross & Levenson, 1993) and other
investigations finding no sex differences (Cupchik & Poulos, 1984; Kring & Gor-
don, 1998; Lanzetta et al., 1976; Wagner et al., 1993; Zuckerman et al., 1981).
Finally, gender may be an important moderating variable in lateralization stud-
ies of emotion, as there is evidence that there is more bilateral hemispheric rep-
resentation of function in women than in men (e.g., Crucian & Berenbaum, 1998;
20 INTRODUCTION
Gur et al., 1982, 1999; McGlone, 1980). Thus, interpretations of findings re-
garding neural correlates of emotion and emotional regulation must take subject
characteristics into account.
Although the emphasis in many neuropsychological studies of emotion has
been on pathological and deficit states, a focus on emotional function (rather than
dysfunction) and the study of positive emotion may also yield important find-
ings. For instance, Tomarken (1998) recently described how pharmacological
treatment of depression may differentially influence the appearance of positive
versus negative affect in depression. Indeed, most studies of emotion have fo-
cused predominantly on negative emotions (see Fredrickson, 1998). Fredrickson
(1998) proposed that positive emotions differ from negative ones in that specific
effector response systems are not elicited by positive emotional states. Rather,
she proposed a "broaden and build" model of positive emotions in which posi-
tive emotions elicit thought/action repertoires that serve to alter attentional focus
and cognitive flexibility. Thus, exploring positive affect in neuropsychological
studies may lead to a richer understanding of emotion in general and may serve
to better predict favorable outcomes in individuals with emotional dysfunction.
In the relatively few neuropsychological studies that examine positive emo-
tion, the findings suggest an involvement of temporal regions. For example, when
true periods of happiness (indicated by a "felt" or Duchenne smile) were elicited
in healthy participants, there was greater activation of left temporal and parietal
regions (Ekman et al., 1990). Similarly, in a case study, laughter and feelings of
mirth were elicited in two patients with gelastic seizures after stimulation of basal
temporal regions, specifically fusiform and parahippocampal gyri (Arroyo et al.,
1993). The findings from functional neuroimaging studies in healthy populations
are less clear and suggest a great deal of overlap between pleasant and unpleas-
ant emotional states (e.g., appetitive and aversive motivational systems) (George
et al., 1995; Lane et al., 1997a,b). Clearly, further work is needed to distinguish
specific neural correlates involved in particular kinds of emotion, especially for
positive emotional states.
Finally, as several of the authors have proposed, neuropsychologists need to
broaden the scope of their research to examine elements of social functioning
and its interaction with emotional processing and regulation. Stuss, van Reekum,
and Murphy (Chapter 14, this volume) note the injurious effects of apathy, with
one subtype leading to "the absence of an abstract model of one's self in soci-
ety" (p. 356). Their work highlights the importance of multifaceted treatments
of such disorders, including both pharmacological and social skill training inter-
ventions. Perhaps models and experimental paradigms from neurodevelopmen-
tal disorders (namely autism) can be used to explore social-emotional function-
ing in other psychiatric and neurological disorders (for review, see Brozgold et
al., 1998). Oschner and Schacter (Chapter 7, this volume) have attempted to un-
derstand how emotion can interact with encoding and retrieval mechanisms of
memory to function within the social context of goals and personal motivations.
Scherer (Chapter 6, this volume) notes the importance of emotional appraisal in
eliciting specific emotions, and much work has been done regarding cultural dif-
ferences in appraisal processes, as in the social-emotional construct view of emo-
tion (e.g., Mesquita & Frijda, 1992). In contrast, to our knowledge, few neu-
ropsychological studies have examined the role of appraisal and its relationships
to other parameters of emotional processing, such as the dimensions of valence and
appetitive-aversive components. A final point regarding social-emotional func-
tioning concerns complex social emotions, like shame, embarrassment, jealousy,
and pride. As Adolphs and Damasio (Chapter 8, this volume) point out, "the next
task will be to elucidate what distinguishes emotion in humans from emotion in
other animals" (p. 209). There are almost no studies examining the role of such
emotions in clinical populations, with the exception of Ross, Homan, and Buck's
study (1994) exploring hemispheric differences between primary and social emo-
tions in epileptic patients. Thus, little is known about the neural correlates of such
complex emotions, and this, too, is another area ripe for future study.
SUMMARY
In summary, there are a number of areas that require further investigation to bet-
ter define brain-behavior relationships in emotion as we enter the new millennium.
These principal themes are echoed and expanded in the chapters that follow.
In terms of theory, greater overlap is needed among theoretical models so that
a more direct comparison among different perspectives can be completed. Of
considerable help would be a "common language" that not only includes careful
definition of concepts but also subscribes to using similar terminology. This
would make it easier for investigators to compare findings across studies. Al-
though it is unlikely that there will be one theory to describe all aspects of emo-
tional processing, having such a common language will be helpful when inte-
grating such information.
With respect to the study of specific emotional disorders, further classification
and subtyping of such disorders is essential to delineate homogenous samples.
In addition, individual differences, which contribute further variability, need to
be taken into account. In any case, it is our hope that specific interventions will
be further refined and developed to treat the gamut of emotional disorders. Fur-
thermore, understanding social emotions, how to promote positive emotions, and
the extent to which these emotions have predictive value in outcome may also
be addressed.
In terms of evaluating emotional processing deficits and their disorders, psy-
chometric studies are needed to examine protocols assessing emotional percep-
tion, expression, and experience. To date, most batteries are either not readily
22 INTRODUCTION
available for clinical use or are not practical to administer within a clinical set-
ting. Such assessment measures will provide valuable information regarding in-
dividual functioning that may otherwise be overlooked.
Functional neuroimaging techniques provide other important assessment tools.
As such methods are further refined and allow for greater temporal clarity with-
out sacrificing spatial resolution, additional areas in emotion research can be ad-
dressed. These include understanding how and when particular neural structures
are normally activated in emotional processing and determining interactions
among these structures. Imaging technology can be used to address questions that
have been debated for decades by emotion theorists, such as the relationship
among modes of processing (e.g., experience vs. expression) and channels of
communication (e.g., facial vs. prosodic). Such tools may also allow a greater
understanding of the exact nature of particular brain regions (e.g., frontal lobes)
in emotional processing. The ultimate goal may be to reconcile paradoxical find-
ings from various techniques (e.g., the brain lesion method, neuroimaging data,
and behavioral data from healthy adults), leading to a richer understanding of the
underlying neural mechanisms involved and the causes of dysfunction.
The following chapters, then, provide new insight into the problems facing in-
vestigators of emotion and into interpretations of the neuropsychological mech-
anisms that underlie emotional processing. The authors' thoughtful presentations,
detailed accounts of the research, and provocative ideas will advance the direc-
tion of future research so that many different dimensions and components im-
portant in emotion processing can be explored in a variety of clinical populations
with a wide range of techniques.
ACKNOWLEDGMENTS
We are very grateful to Jack Nitschke, Ronald Bloom, and Sarah Raskin for their insightful com-
ments and input into this chapter.
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II
BACKGROUND AND
GENERAL TECHNIQUES
2
The Epistemology of Reason and Affect
ROSS W. BUCK
The overwhelming question in neurobiology today is the relation

between the mind and the brain.
(Crick & Koch, 1997, p. 19)
Emotions have traditionally been regarded as extras in psychol-

ogy, not serious mental functions like perception, language,
thinking, learning.
(Oatley & Jenkins, 1996, p. 122)
Contemporary investigators interested in the relationship between mind and

brain and in the associated questions of knowledge, experience, and con-
sciousness have for the most part centered on higher order cognitive functions—
what Oatley and Jenkins (1996) in the above quotation termed serious mental
functions—and have eschewed the detailed consideration of emotion. Histori-
cally, however, emotion more than other psychological phenomena has been
intimately connected with the mysterious "mind stuff of subjective experi-
ence. As B.F. Skinner (1953, p. 257) noted, such "private events" are outside
the realm of objective observation: They are defined by their "limited accessi-
bility (to the community) but not, so far as we know, by any special structure
or nature."
Some advances in the techniques of observing the neurochemical correlates
of emotion are relevant to the understanding of subjective experience in gen-
eral, perhaps making consciousness itself more accessible to objective scrutiny.
With this accessibility, comes the opportunity to accommodate our theories to
these new observations: to develop a more consensual, formal language with
which to describe subjective experience, consciousness, and knowledge. To ex-
plore the implications of the new advances in the observation of subjective
events, this chapter examines how the public/private distinction has been drawn
and the nature of meanings attributed to private events, in modern conceptual
31
32 BACKGROUND AND GENERAL TECHNIQUES
philosophy.1 The chapter outlines the history of philosophical conceptualiza-

tions of cognitive and emotional meaning, specifically those of pragmatism,
positivism, and ordinary language philosophy, and discusses these with regard
to recent advances in understanding the neurobiological bases of emotion.
EPISTEMOLOGY AND NEUROBIOLOGY
Epistemology is the theory of the origin, structure, and validity of knowledge

and has generally been considered a branch of philosophy (Runes, 1962). In mod-
ern philosophy there is a fundamental distinction between knowledge and dis-
course that is open to public verification and knowledge and discourse that is
not. The epistemological validity of the latter is in dispute: Some consider it to
be "meaningless," while others acknowledge that, under some circumstances,
what have been termed emotive knowledge and discourse have meaning and
value. Historically, this debate has been influenced by the degree to which ad-
herents of the different positions recognized the importance of biological
processes in thinking and knowing. By and large, those conceptual philosophers
who saw value in emotive knowledge were more influenced by biology, partic-
ularly Darwin's theory of evolution, and they tended to define the value of emo-
tive knowledge in biological terms.
As conscious experience and thought were increasingly associated with the
functioning of the brain, neurological epistemology arose from "a need to deal
with epistemology on a neurological basis" (Kuhlenbeck, 1965, p. 147).
MacLean (1990) coined the term "epistemics" for the study of the subjective
brain. Clearly, the facts of neural organization set constraints for epistemology
(LeDoux, 1994a, 1996). Moreover, advances in the capacity to observe emo-
tional phenomena—both in the neurology of emotional responding in the brain
and in the observation and analysis of the nuances of emotional expression—
have opened aspects of private consciousness that were heretofore closed to pub-
lic verification. Skinner in fact anticipated such advances in his analysis of pri-
vate events. He wrote, "The line between public and private is not fixed. The
boundary shifts with every discovery of a technique for making private events
public" (Skinner, 1953, p. 282). These observations are fundamental to under-
standing the epistemological validity of emotional knowledge. This new under-
standing offers opportunities both to examine the adequacy of philosophical con-
ceptualizations and to use those conceptualizations to identify important
1
Experientialphilosophers, such as the existentialists, also have much to say about consciousness
and emotion, but their views are not considered here due to space limitations. See, for example, Sartre
(1948, 1957).
The Epistemology of Reason and Affect 33
questions in the neurobiology of emotion that may have thus far gone unan-
swered, or unasked.
PHILOSOPHICAL CONCEPTUALIZATIONS OF
COGNITION AND EMOTION
Classical Roots: Monism and Dualism
Since the time of classical Greece in the fifth century B.C., Western thought has
distinguished between animalistic energies characteristic of the body and ratio-
nal processes associated with "mind" or "soul" unique to human beings. In this
dualistic position, mind and soul were seen as immaterial and beyond investi-
gation except by rational means, that is, by metaphysical speculation. A con-
trasting idea of materialistic monism, that there is only matter, also appeared in
early Greek thought but had less influence at the time. Examples of dualistic
thinking are found in the writings of Plato and Aristotle, who presumed that non-
human animals have rudimentary "souls" capable of dealing with basic bodily
functions but not "rational souls," which were the foundation of human reason
and logic. Aristotle distinguished three grades of soul: the vegetative, found in
all living things; the sensitive, characteristic of animals and humans; and the ra-
tional, possessed only by humans. Following his example, Thomas Aquinas
equipped humans with both a "sensitive soul," shared with animals, and a ratio-
nal soul (Cofer & Appley, 1964).
In Meditations (1641), Rene Descartes contributed the first systematic con-
ceptualization of the interaction between mind, or soul, and body. The body is
mechanical, public, tangible, visible, and extended in space; the mind/soul is pri-
vate, intangible, and invisible. Descartes distinguished between nonhuman ani-
mal behavior, which could be accounted for by the reflex-like actions of me-
chanical "animal spirits," and human behavior, which was partly mechanical but
partly influenced by a rational soul. In his conception, a rational soul makes con-
tact with the body at the pineal gland. Conscious sensation occurs when the ra-
tional soul becomes aware of the animal spirits: body affecting mind. Conversely,
the rational soul can alter the flow of animal spirits: mind affecting body (Woz-
niak, 1992). This interaction between spatial body and unextended mind cannot,
for Descartes, be comprehended in either spatial or nonspatial terms: It is beyond
our capacity to understand. This dilemma has been termed the Cartesian impasse
(Vesey, 1965) and is reflected perhaps in the "explanatory gap" acknowledged
in contemporary theories of consciousness (see Chalmers, 1995; Clark, 1995).
The philosophic tradition from Descartes flowed in two streams: the rational-
ism of Spinoza and Leibniz and the empiricism of Locke, Berkeley, and Hume.
Both rationalists and empiricists recognized both analytic statements of logic and
mathematics and synthetic statements of fact and regarded this classification as
mutually exclusive. To Hume, it was mutually exhaustive as well: Metaphysical
speculation that was neither analytic nor synthetic could be nothing but "sophistry
and illusion" (Levi, 1959, p. 333). This argument was to support and sustain a
resurgence of materialistic monism in the form of positivism.
Pragmatism
American pragmatism derived its emphasis on science and "hard" facts from the
tradition of British empiricism. This was combined, however, with the idea that
truth is not absolute and that when we say "this is true" we mean that it is use-
ful in some way (Hill, 1961). This doctrine of the functional nature of truth re-
flected a basic compatibility between pragmatism and evolutionary theory.
Pragmatism has ties to nineteenth century idealism in its doctrine that the
knower conditions the known: "reality is and can be nothing more than reality-
as-known. . . . '[O]bjective' reality is nothing but the most inclusive and co-
herent system of ideas that the human mind can entertain" (Aiken, 1962a, p. 54).
The mind is conceived of as an active agent, not a passive acceptor of sense data.
What is "given" in experience is already invested with meaning and significance.
A related similarity with idealism is the notion that ideas relate to their cultural
and historical context. Furthermore, ideas are purposive: They are always goal-
oriented and change with our needs and interests. These themes occur also in re-
cent contextualism and hermeneutic analysis (Taylor, 1992). The pragmatists,
however, differ from the idealists and recent theorists in their empirical and be-
havioral concept of mind and in their emphasis on sense perception and the guid-
ance of the scientific method (when practical) as the best way to reach the ob-
jectives of thought. Also, the influence of Darwin's theory on pragmatism placed
its spirit worlds apart from that of idealism. Pragmatists regarded thought to be
a product of the natural order and conceived of it in essentially biological terms
(Aiken, 1962a).
Early nineteenth century philosophy was dominated by what William James
was to term "tender-minded" philosophies, such as Emersonian trancendental-
ism in the United States and neo-Hegelian idealism in England. Darwin's Ori-
gin of Species (1859) and other scientific advances threatened the adherents of
these philosophies: They had to defend their concerns for inner self and spiritual
values against the encroachments of positivistic and materialistic scientism, which
were supported by Darwin's findings and were actively advanced by Darwinists
such as Spencer. The pragmatists did not accept either of the "two extremes of
crude naturalism on the one hand and transcendental absolutism on the other"
(James, 1907, p. 301). They looked consciously for a position that would rec-
oncile these points of view (White, 1955).
C.S. Peirce
C.S. Peirce is regarded by many as the founder of pragmatism. In his prag-

matic theory of meaning, Peirce (1877/1962) argued that meaningful proposi-
tions must be transformable into hypothetical, operational, experimental state-
ments. Propositions must be translatable into the hypothetical form: "If operation
X were to be performed on this, then E would be experienced." The "if" clause
must mention an operation performed by the experimenter, and the "then" clause
must mention something experienced or observed when the testing conditions
are met. This procedure tells what a word denotes by "prescribing what you are
to do in order to gain a perceptual acquaintance with the object of the word"
(Peirce, quoted in White, 1955, p. 157). If a proposition resisted translation into
the proper form, it was considered scientifically meaningless, although it may
evoke images or emotions (White, 1955).
Peirce suggested that the pragmatic theory of meaning rendered meaningless
many statements in traditional metaphysics and theology and that, moreover, the
theory would show many disputes in philosophy to be pseudoarguments over
words or concepts that are pragmatically identical, that is, have the same opera-
tional translations. His theory of meaning contributed to the verifiability crite-
rion of meaning of the positivists and to the operationism of P.W. Bridgman
(1938), S.S. Stevens (1935) and others.
William James
Peirce's pragmatic theory of meaning was borrowed and modified by William

James, who used it in his attempt to reconcile "tender-minded" and "tough-
minded" doctrines in philosophy. James offered pragmatism as a "new name for
some old ways of thinking" that can satisfy both the demands of the spirit and
the demands of fact. He contrasted tender-minded rationalism with tough-minded
empiricism, where rationalism "starts from wholes and universals, and makes
much of the unity of things" and empiricism "starts from the parts, and makes
of the whole a collection" (James, 1907, p. 11).
In The Principles of Psychology, James (1890) accepted the idea that good sci-
ence was positivistic: that everything scientifically knowable is public and that
an objective psychology must eliminate subjective factors. In the mid-1890s, he
began to revise this idea based on evidence from psychopathological conditions
involving emotion and subconscious states. He critiqued scientific materialism
with a metaphysics of radical empiricism, which was empirical in that it con-
fined itself to the facts of experience but radical in that it demanded that science
not ignore any experience, including emotional experience (Taylor, 1992). James
reinterpreted the foundations of science and religion in his pragmatic theory of
truth. In the process, he broadened the meanings of Peirce's words "operation"
and "experience" so that the operation to be performed was a belief in something
and the desired experience was a feeling of satisfaction. Thus the statement "S is
true" is translated into "if you believe S, you will experience a feeling of satisfac-
tion." The "meaning" lies in those experiences to which the belief, if true, will lead.
Verification consists of the occurrence of those experiences (White, 1955).
James' reformulation enabled him to formulate an original theory of meaning,
truth, and verification that threw light on many speculative statements bypassed by
Peirce. The choice between belief and disbelief in God is meaningful because the
adoption of one alternative would lead to different life experiences than the choice
of the other (Hill, 1961). Thus, subjective human experience was taken as the ul-
timate test of truth. This implication led James to be hailed as a savior by some
and to be brutally caricatured by others. Peirce dissociated himself from James'
formulation by renaming his own view "pragmaticism," a term he described as
"ugly enough to be safe from kidnappers" (quoted in White, 1955, p. 158).
White (1955, p. 159) summarized James' position succinctly: "The true is what
we ought to believe. That which we ought to believe is what is best for us to be-
lieve. Therefore, the true is that which is best for us to believe." This view, how-
ever, reflected an ambiguity in utilitarian ethics: What is best for whom? James
often answered "the individual," but, as Peirce stated in a letter to James, "What
is utility, if it is confined to a single person? Truth is public" (quoted by White,
1955, p. 159). This is the particular theme of pragmatism emphasized by John
Dewey.
John Dewey
To Dewey, James' account of truth was too individual and capricious. Dewey
used Peirce's pragmatic theory of meaning as the foundation for a theory of so-
cial and public morality. Where James used pragmatic theory to explain the
"true," Dewey used it to explain the "good" and, with George Santayana, the
"beautiful" as well (White, 1955). Dewey offered an ethical theory that, like
James', attempted to steer a moderate course between ideas of "transcendent eter-
nal values" and the "empirical" view that value is defined by mere personal lik-
ing, desire, enjoyment, or interest.
Peirce's question of "what is best for whom?" can be viewed in terms of Dar-
win's theory: What is best is that which promotes successful adaptation. The idea
of adaptation is consonant with pragmatism, and indeed Dewey approached the
idea of public good from a Darwinian point of view. He wrote that Darwinism
"led straight to the perception of the importance of distinctive social categories
especially communication and participation." He continued, arguing that "a great
deal of our philosophizing needs to be done over again from this point of view,
and that there will ultimately result an integrated synthesis in philosophy con-
gruous with modern science and related to actual needs in education, morals, and
religion" (Dewey, 1931, p. 3). One of his contributions was the idea of a "prob-
lematic situation," which was at once biologically rooted and socially enveloped.
Conclusions
In pragmatism, one finds the idea of knowledge as a product of the natural or-
der, suggesting that emotional knowledge may be evaluated according to bio-
logical criteria. Also, the essence of scientific methodology is distilled in Peirce's
operationism: that to be scientifically meaningful, a proposition must be trans-
latable into an operation that must reliably produce an observation or experi-
ence. James extended this so that emotional experiences—for example, of
satisfaction—could be used as criteria of meaning and truth. Dewey and others
suggested that common values, not individual satisfaction, be used as the crite-
rion not of "truth" but of "good" and "beauty." While James' and Dewey's con-
ceptions tended to moderate and expand the venue of Peirce's operationism into
the realm of emotional meaning, the logical positivists applied it much more
strictly and rigorously.
Positivism
Positivism is the doctrine that the highest form of knowledge is a simple de-
scription of sensory phenomena (Carnap, 1937; Runes, 1962). In contrast with
the pragmatists, the positivists of the early twentieth century based their con-
ceptualizations on mathematics and logic: They tended to be uncompromisingly
"tough-minded" and were not greatly influenced by biological thinking. In log-
ical positivism was found most directly the faith that human beings come to
knowledge through erecting abstract concepts that are based ultimately on pub-
licly verifiable operations. The positivists considered that difficulties arise when
concepts are not clearly grounded in observations. They considered the function
of philosophy to be analysis and clarification, and a major goal of the early pos-
itivists was to construct a perfectly simple, clear, and logical artificial language
for science that could clarify scientific statements, free of the entanglements of
ordinary language. Judgments of value and beauty and statements expressing
feeling were seen to be devoid of cognitive content and were largely ignored.
English neorealism
Bertrand Russell and Alfred North Whitehead formulated the basis for the
analysis and construction of ideal, artificial systems of language, logic, and math-
ematics in three volumes of Principia Mathematica (1910-1913). Their objec-
tive was to demonstrate that mathematics is derivable from logic, and they in-
troduced technical innovations that both contributed to modern symbolic logic
and gave positivism a methodology and the model for an artificial but unam-
biguous symbolic language (Levi, 1959).
Another major contribution of Russell to positivism was his logical atomism
in which he attempted a logical reconstruction of physics. This described the
physical universe as if it could be described in terms similar in form to those in

Principia Mathematica. "Logical atoms" were independent, primitive notions
used to describe the rest of the universe. It was reasoned that, if the truths of
mathematics, science, and common sense can be dealt with in a logically perfect
language, it would allow us to know precisely what we are saying and whether
it is logically true. The presupposition is that the world of logical discourse is
similar in structure to the world of fact and that the elimination of internal in-
consistency in the one will provide a clue to the structure of the other. It is in
terms of logical atoms that a perfectly logical scientific language would describe
the world (Aiken, 1962b; Levi, 1959).
Between 1911 and 1913, the Austrian Ludwig Wittgenstein was at Cambridge
and came under the influence of the new logic. In 1922 he published Tractatus
Logico-Philosophicus, which was a radical restatement of Russell's logical atom-
ism. Wittgenstein argued that statements that describe or mirror atomic facts are
the basis of science. A perfect scientific language would provide a mirror for the
structure of reality. Ordinary language cannot provide this mirror because it con-
tains impossible problems of meaning and implication. It is for this reason that
philosophical analysis exists. Given a logically perfect language, as approximated
in Principia Mathematica, statements could be mechanically reduced to their ba-
sic atomic facts. This language would resemble a calculus, with clear and sim-
ple basic terms (Aiken, 1962b). Wittgenstein distinguished between factual, or
synthetic, and logical and mathematical, or analytic, propositions. The latter are
always tautologies and tell us nothing about the world. They merely tell us what
we can infer from true and false statements (Barrett, 1962).
The Vienna Circle

Wittgenstein's logical atomism and distinction between analytic and synthetic
propositions impressed a group of philosophers in Vienna. The "Vienna Circle"
was founded in 1923 in a seminar organized by Moritz Schlick. Its most impor-
tant period began in 1926, when Rudolf Carnap joined the university faculty. The
Circle published a manifesto in 1929 and a periodical, Erkenntnis, beginning in
1930. In 1938, the group broke up with the fall of Austria to the Nazis (Levi,
1959).
The classic viewpoint of the positivists of the Vienna Circle was summarized
by Levi (1959, pp. 344-345). It included the proposition that "all cognitively sig-
nificant (meaningful) discourse is divisible without remainder into analytic or
synthetic propositions." This asserts the crucial distinction between the tautolo-
gous statements of logic and mathematics and the factual statements of the sci-
ences, which are considered probably true or probably false. Also, "any propo-
sition that purports to be factual or empirical has meaning only if it is possible
in principle to describe a method for its verification." This is the verifiability cri-
terion, closely related to Peirce's criterion of meaning. Furthermore, "all meta-
physical assertions, being neither analytic nor synthetic, are meaningless" and
"all normative assertions ... are scientifically imverifiable, and are therefore to
be classified as forms of non-cognitive discourse." Noncognitive discourse was
termed emotive discourse. Emotive statements are not meaningless, for they ex-
press how we feel, but they are not "cognitive" (Levi, 1959).
When the Vienna Circle was formed, the positivists thought that they were
absolutely right and were spoiling for a fight with other positions. At this time,
their principal weapons were simplicity and clarity (Bochenski, 1961). Begin-
ning in the mid-1930s, however, the positivists came to realize that things were
not as clear and simple as they had seemed. Their methods were found to be
quite limited, and they were forced to become more flexible, moving in the
process toward "a rapprochement with pragmatism" (Barrett, 1962, p. 13). On
of the changes in the positivist outlook reflected the fact that their definition of
cognitive discourse was so restrictive that large areas of experience remained un-
touched. The neat analytic-synthetic dualism did not deal with the meaning of
"emotive discourse," including value statements like "the painting is beautiful"
as opposed to the cognitive statement "the painting is red." Also, statements
feeling, while seen as "noncognitive" were not held to be meaningless.
The Analysis of Ordinary Language
Ludwig Wittgenstein
Wittgenstein eventually abandoned the attempt to develop an ideal artificial

language and became skeptical of the very foundation of Principia Mathemat-
ica. Possibly this was in part a result of Goedel's 1933 theorem proving the in
completeness of mathematics: that any mathematical system must contain true
but unprovable statements (Levi, 1959). This discovery revealed mathematics in
a light different from what Wittgenstein had seen in Tractatus: The tautological
character of mathematics was no longer so clear (Barrett, 1962). Instead, Wittgen-
stein came to agree with G.E. Moore that the common sense statements of ordi-
nary language are the proper objects of analysis (Aiken, 1962b).
Rather than pursue unattainable ideals of simplicity and clarity by analyzing
unreduceable "logical atoms" and a fixed syntactic calculus, Wittgenstein came
to see language as inevitably complex and organic (1965). The forms of words
do not represent the structures of things; instead, they represent forms of life
(Aiken, 1962b). Wittgenstein compared language to "an ancient city: a maze of
little streets and squares, of old and new houses . . . surrounded by a multitude
of new boroughs with straight regular streets and new houses" (Levi, 1959, p
436). Instead of reforming language, Wittgenstein now sought to understand it.
Central to his new conceptualization was the idea of "language games."
Wittgenstein suggested that it is pointless to search for a common element in all
that we call "language." The elements of language are related to one another in
myriad ways, and one common relationship cannot be found. "Language" is the
name of these related elements, just as "games" is not an expression of some
common trait that can be found in all of the activities that we call "games." That
series of relationships and similarities, overlapping and crisscrossing like the
twisted fibers, makes up the thread called "language" or "games." This thread of
similarities is termed a "family," exhibiting "family resemblances," rather than
a unitary "essence" that characterizes all examples of the phenomenon of "lan-
guage" or "games" (Wittgenstein, 1953).
This concept of language gave Wittgenstein a new viewpoint on philosophi-
cal puzzles and their resolution. He became interested in the things that drive
philosophers into bizarre and maddening enigmas, suggesting that the origin of
such riddles stems from the improper use of language and that such riddles can
be eliminated only by the meticulous analysis of language as it is actually used
(White, 1955). "Philosophy," he said, "is a battle against the bewitchment of our
intelligence by means of language" (Levi, 1959, p. 441).
Gilbert Ryie: The ghost in the machine

One such enigma is the Cartesian impasse: the incomprehensible idea of a
purely spiritual mind joined somehow to a purely material body. Gilbert Ryle
(1949, pp. 15-16) ridiculed this as the "dogma of the ghost in the machine." Ryle
argued that the "Cartesian myth" is an illusion arising from an improper use of
language. Specifically, he argued that speaking of mind as if it were a substance
in the same logical category as the body is a category error analogous to speak-
ing of "the university" as if it were a substance of the same logical category as
classrooms, laboratories, libraries, and the like. Actually, mind is an organizing
principle of a different logical type than the body, just as the university is an or-
ganizing principle encompassing its constituent elements. He noted that the the-
oretically interesting category mistakes are those where people are perfectly com-
petent in applying a concept in ordinary life but have difficulty when thinking
abstractly about the concept, relating it inappropriately with other abstract
concepts.
Ryle (1949, p. 83) singled out the realm of emotion as one where Cartesian
thinking is particularly intractable: Most philosophers and psychologists, he
noted, view emotions as "internal or private experiences. . . . They are occur-
rences that take place not in the public, physical world but your or my secret,
mental world." Ryle suggested that the word "emotion" is used to designate four
different kinds of things, including inclinations (or motives), agitations (similar
to conflicts), moods, and feelings. He argued that inclinations, agitations, and
moods are "not occurrences and do not therefore take place either publicly or
privately. They are propensities, not acts or states" (Ryle, 1949, p. 83). Thus brit-
tleness is a propensity of glass to break when struck. Although we may say "the
glass broke because it is brittle" or "the glass broke because it was struck," only
the latter statement denotes an occurrence. Ryle (1949, p. 83) continued: "feel-
ings, on the other hand, are occurrences, but the place that mention of them should
take in descriptions of human behaviour is very different from that which the
standard theories accord to it." He noted that James defined feelings in terms of
bodily sensations, but wrote "for our purposes it is enough to show that we talk
of feelings very much as we talk of bodily sensations, though it is possible that
there is a tinge of metaphor in our talk of the former which is absent from our
talk of the latter" (Ryle, 1949, p. 84).
Ryle suggested that feelings are signs of agitations and offered an analogy
with a stomach ache as a sign of indigestion. He asserted that there are no nec-
essary or sufficient criteria for either: "[Feelings] are signs of agitations in the
same sort of way as stomach-aches are signs of indigestion. Roughly, we do not,
as the prevalent theory holds, act purposively because we experience feelings;
we experience feelings, as we wince and shudder, because we are inhibited from
acting purposively" (Ryle, 1949, p. 106). He goes on, "we can induce in our-
selves genuine and acute feelings by merely imagining ourselves in agitating cir-
cumstances. Novel-readers and theatergoers feel real pangs and real liftings of
the heart, just as they may shed real tears and scowl unfeigned scowls. But their
distresses and indignations are feigned. They do not affect their owners' appetites
for chocolates, or change the tones of voice of their conversations. Sentimental-
ists are people who indulge in induced feelings without acknowledging the fic-
titiousness of their agitations" (Ryle, 1949, p. 107).
Discussion
Ryle hoped that the proper use of language would resolve the Cartesian impasse,
but that particular quandary remains: In the words of Crick and Koch (1997, p.
19), "the overwhelming question in neurobiology today is the relation between
the mind and the brain." The new ability to observe brain functioning may, how-
ever, allow us to reformulate the issues in useful ways. In this regard, Barrett
(1962, p. 62) pointed out that there are "large areas of experience where our lan-
guage is not yet ripe for any significant attempt at formalization." As areas
amenable to public observation expand with improved techniques for "making
private events public," in Skinner's words (1953, p. 282), formalization of lan-
guage will naturally follow. Arguably this is occurring today in the realm of emo-
tion theory.
In this regard, Barrett (1962, p. 17) also suggested that the positivistic under-
standing of "cognitive" is constructed on an overly narrow model. He described
and critiqued the positivists' position on feeling and emotion, noting that in their
writings feelings are "some kind of subcutaneous twinges, throbs, or tremors that
in some odd way lie on the opposite side of mind from intellect and reason, which
are the truly cognitive faculties." But, he pointed out, "Ordinary language con-
tains plenty of uses where we speak of knowledge in connection with the pres-
ence of feeling and ignorance in connection with its absence." He concluded,
"Feeling is not a blind stab or spasm of some psychic substance underlying mind,
but a form of consciousness that, like every other mode of consciousness, has its
own intentionality and revelation."
Barrett's critique (1962) of the positivist view of cognition and emotion is
compatible with recent analyses of emotion as constituting a type of cognition.
Arguably emotional knowledge is functional—it has survival value in an evolu-
tionary sense—and is "meaningful" from the pragmatic perspective. The next
section considers the nature of emotional and cognitive knowledge from a neu-
robiological viewpoint.
EMOTIONAL AND COGNITIVE KNOWLEDGE
We have seen that many modern philosophers have considered "emotion" and
"cognition" to be mutually exclusive, with cognition being associated with pub-
lic knowledge and discourse and emotion consigned to a "noncognitive" private
knowledge of doubtful epistemological status. Recent research in the neuro-
sciences has afforded a greater objective understanding of how the brain processes
underlying what have traditionally been termed emotional and cognitive knowl-
edge differ, and this understanding offers insights into the functions of this knowl-
edge. More specifically, there is evidence that "emotion" and "cognition" differ
in level and speed of brain processing.
Level of Brain Processing
In 1927, Bertrand Russell anticipated a major contemporary theory of emotion

in an account of a visit to a dentist. Russell (1927, p. 226) discussed the "radi-
cal transformation" in the theory of emotion wrought by Cannon (1915), sug-
gesting that certain endocrine secretions are the "essential physiological condi-
tions of the emotions." The dentist had injected adrenaline in the course of
administering a local anesthetic. Russell (1927, pp. 226-227) wrote: "I turned
pale and trembled, and my heart beat violently; the bodily symptoms of fear were
present, as the books said they should be, but it was quite obvious to me that I
was not actually feeling fear. . . . What was different was the cognitive part: I
did not feel fear because I knew that there was nothing to be afraid of."
The idea that emotion involves an interaction between "cognitive" and "phys-
iological" factors was the basis of the well-known Schachter and Singer (1962)
study and self-attribution theory of emotion. This theory suggested that cogni-
tive elements are responsible for the qualitative aspects, and physiological fac-
tors the quantitative aspects, of emotion. Russell recognized, however, that "phys-
iological" factors could be responsible for qualitative aspects of emotion as well.
He suggested that some emotions such as melancholia, "presumably, can be
caused in their entirety by administering the proper secretions" (Russell, 1927,
p. 227).
We now know that the physiological bases of emotion involve far more than
the autonomic and endocrine systems: There are basic emotion circuits that re-
flect primal survival demands, prompting rapid and coherent responses. These
interact with higher level brain systems that contribute increased flexibility that
can reflect strategic considerations (Panksepp, 1994a).
Speed of Brain Processing
The Zajonc-Lazarus debate

The question of the speed of emotional processing was central to one of the
classic debates in recent emotion theory, concerning whether "emotion" precedes
or follows "cognition." The Zajonc-Lazarus debate is instructive both because it
illustrates how differences in the use of language and the definition of terms can
produce apparent theoretical quandaries with devout adherents on both sides and
because it was resolved by the results of neurobiological research.
The debate began with evidence that subjects could respond preferentially to
stimuli without "knowing" what they were: Familiar nonsense syllables and
ideograms were rated more positively even though subjects could not recognize
them as familiar. On this and other evidence, Robert Zajonc (1980, 1984) argued
that affect occurs before, and independently of, cognition. His argument drew a
strong response from Richard Lazarus (1982, 1984), who argued, based on his
own research, that emotion could not occur without prior "cognitive appraisal."
Examination of the arguments of Zajonc and Lazarus reveals that their dis-
agreement rests on how each defined "cognition." Both had developed verifiable
operational definitions of the construct "cognition," but what was not immedi-
ately apparent was that these operations were quite different. Zajonc (1984) de-
fined cognition as involving some kind of "mental work": some transformation
of sensory input or information processing. For Lazarus, cognition could involve
a "primitive evaluative perception" (1984, p. 124) that was "global or spherical"
(1982, p. 1020). In effect, both Zajonc and Lazarus agreed that some sort of sen-
sory information is necessary for emotion, but they disagreed on what would con-
stitute "cognition."
The LeDoux resolution

The Zajonc-Lazarus debate was resolved by the findings of LeDoux and his
colleagues that fear involves an interaction between fast processing associated
with the amygdala and slower but more elaborate representation associated with
the neocortex. Specifically, stimuli reach the amygdala directly via the thalamus:
a short and fast route. Because it bypasses the cortex, the amygdala receives di-
rectly only a "crude, almost archetypical" representation of the stimulus, which
is shortly followed by a more accurate representation involving cortical pro-
cessing (LeDoux, 1996, p. 166). This neural organization indicates that we "be-
gin to respond to the emotional significance of a stimulus before we fully rep-
resent that stimulus" (LeDoux, 1994a, p. 221).
LeDoux (1996, p. 202) also found that the memories of fearful experiences in-
volve at least two sorts of neural organization: an implicit emotional memory sys-
tem associated with the amygdala and a declarative or explicit memory system
associated with the hippocampus that is associated with conscious recollection.
These normally operate simultaneously and in parallel, but their functioning can
be dissociated in experimental animals and in rare case studies in human beings
(LeDoux, 1994b).
LeDoux's data suggest that both Zajonc and Lazarus are correct, but the for-
mer limits the definition of "cognition" to the slower, representational process
and the latter regards the initial fast response as "cognitive." In any event, the
labeling becomes trivial once the neural organization is understood. However we
choose to label what goes on (relatively) early and late in the response to events,
there is a fast initial response that biases slower representational processing and
a more elaborate processing that feeds back and alters the fast response.
MOTIVATION, EMOTION, COGNITION, AND KNOWLEDGE
The LeDoux resolution of the Zajonc-Lazarus debate suggests how language can
become trivial once we understand the neural organization underlying what we
call emotion and cognition, and objective neurobiological investigation has the
potential to inform other semantic puzzles as well. At that level of understand-
ing, what Barrett (1962) termed the formalization of language becomes possible,
and we move away from everyday language toward a more specific variety more
like the sort championed by the positivists. The formalization of language in a
given area of inquiry follows naturally upon public verifiability of fundamental
phenomena in that area. If phenomena are not publicly observable, it does not
necessarily mean that discourse concerning them is meaningless but rather that
consensual and accurate communication using such discourse is difficult to
achieve because of the slippery nature of language. Verifiability lays the ground-
work for formalizing language, but at the same time the language per se in a
sense becomes less important. If a theoretical statement is testable it is also triv-
ial, in the sense that it is the testing that is really important. This was demon-
strated by the definition of cognition being rendered secondary to the operations

employed in LeDoux's research.
Before we do fully understand a psychological phenomenon objectively at the
level of public verification, however, language is anything but trivial. It is all we
have to communicate and attempt to come to an understanding about that phe
nomenon, including how to come eventually to measure it. The criteria for mean-
ing in such discourse remain the classic criteria of rhetoric: the internal consis-
tency of the argument; its cogency, cohesiveness, clarity, simplicity, fruitfulness,
eloquence. Some aspects of human experience may forever remain in the realm
of the poet or experiential philosopher, whose only tools are language: perhaps
the more "emotive" the better.2
The remainder of this chapter considers the language used to describe the ori-
gin, structure, and validity of knowledge, taking into account recent observations
involving emotion in the behavioral and neural sciences. It is suggested that "emo-
tion" and "cognition" are not in fact distinct phenomena: that emotion always in-
volves cognition and, more controversially perhaps, cognition always involves
emotion. Furthermore, both emotion and cognition always involve "motivation"
and vice versa. In the following, conceptual definitions for, and interactions be-
tween, "motivation," "emotion," and "cognition" are laid out.
Defining Motivation, Emotion, and Cognition
Developmental-interactionist theory attempts a unified conceptualization of mo-

tivation, emotion, and cognition based on the assumption that one cannot coher-
ently describe or define "motivation," "emotion," or "cognition" without con-
sidering both of the other terms. Each is involved in both of the others: Motivation
intrinsically involves emotion and cognition, cognition involves motivation and
emotion, and emotion involves motivation and cognition (Buck, 1985).
Motivation and emotion
Motivation is defined as the potential for behavior that is built into a system
of behavior control and emotion as the manifestation or readout of motivational
potential when activated by a challenging stimulus (Buck, 1985, 1988, 1994a;
Buck et al., 1997). The relationship between emotion and motivation is seen to
be analogous to that between matter and energy in physics. Energy is a poten-
tial that is not seen in itself but rather is manifested in matter: in heat, light, force,
and so forth. The energy per se is never shown. Similarly, motivation is con-
ceptualized as a potential that is not seen in itself but rather is manifested in emo-
2
Emotion can be communicated spontaneously via biologically based sending and receiving mech-
anisms. This topic is beyond the scope of this chapter, but see Buck and Ginsburg (1997) for a dis-
cussion of the evolutionary epistemology of empathy.
tion. Motivation and emotion are thus seen as two sides of the same coin or as
aspects of a common core phenomenon: the motivational-emotional system. Phy-
logenetically structured primary motivational-emotional systems (primes) are
considered to be "special-purpose processing systems" that over the course of
development interact with "general purpose processing systems" that reflect the
capacity of the species for learning via classical conditioning, instrumental learn-
ing, higher order cognitive processing, and, in human beings, language.
Cognition
Cognition is defined as knowledge that is based on "raw" awareness or
knowledge-by-acquaintance. This basic knowledge, driven and guided by
motivational-emotional systems, is spontaneously restructured into representa-
tional knowledge-by-description over the course of development (Piaget, 1971).
Knowledge-by-acquaintance was described by Bertrand Russell (1912/1959, p.
46) as the presentational immediacy of experience that is completely self-
evident. William James (1890/1952, p. 144, italics in the original) noted: "I know
the color blue when I see it, and the flavor of a pear when I taste i t . . . but about
the inner nature of these facts or what makes them what they are, I can say noth-
ing at all. I cannot impart acquaintance with them to any one who has not made
it himself." Thus knowledge-by-acquaintance is always "true," or veridical, in a
sense. In contrast, knowldege-by-description is not self-evident and can be false.
Knowledge-by-acquaintance constitutes the raw data of perception based on per-
ceptual systems evolved to detect information in the form of stimulus energy: in
light, vibration, and volatile chemical substances physically present in the envi-
ronment (Gibson, 1966,1979). James J. Gibson's theory of ecological realism pro
vides a coherent and detailed account of the evolution of knowledge from the ear-
liest organisms to human perception. Gibson (1979, p. 255) termed raw perception
awareness: "To perceive is to be aware of the surfaces of the environment and of
oneself in it." Awareness is direct, self-evident, and nonrepresentational: "percepts
qua percepts are the ultimate actualities and are not experienced as representing
something else. . . . " (Kuhlenbeck, 1965, p. 144. Italics in the original).
According to Gibson, species evolved to be sensitive to those aspects of the
environment that afford possibilities or opportunities for behavior: affordances.
There are three sorts of "raw" awareness. First, there is awareness of affordances
in the terrestrial environment, such as those provided by physical objects as sup-
port, obstacles to motion, and so forth. Second, there is awareness of social af-
fordances provided by other animals: "other animals afford, above all, a rich and
complex set of interactions, sexual, predatory, nurturing, fighting, playing, co-
operating, and communicating" (Gibson, 1979, p. 128). Emotional displays can
be considered to be social affordances (Buck, 1984; Buck & Ginsburg, 1997;
McArthur & Baron, 1983). Third, Gibson (1966, p. 31) recognized awareness
via interoceptors of vague sensations of internal origin—feelings and emotions—
the "pangs and pressures of the internal environment." These may be conceptu-
alized as bodily affordances, and in the present view subjectively experienced
affects—feelings and desires—constitute awareness of bodily affordances.
In contrast to raw awareness or knowledge-by-acquaintance, knowledge-by-
description is representational, constructed from the restructuring or processing
of raw perceptual data. Thus we have direct perceptual acquaintance with events
in the terrestrial environment, social environment, and internal bodily environ-
ment and representational knowledge about these events based on information
processing and inference. Agnosias, where elementary perception is intact but
"stripped of meaning" (Bauer, 1984, p. 457), might constitute an inability to trans-
fer specific sorts of knowledge by acquaintance into knowledge-by-description
(Buck, 1990).
Affect
The subjective experience of emotion involves a direct interoceptive knowl-
edge-by-acquaintance of bodily processes serving functions of self-regulation.
"Bodily processes" in this context do not refer to feedback from autonomic re-
sponses or expressive behaviors; rather, they are specific neurochemical systems
of internal perception that have evolved to inform the organism of functionally
important events in the bodily milieu. The experiential aspects or qualia associ-
ated with these interoceptive perceptual systems are feelings and desires (Buck,
1993). The events of which they inform include needs for food (hunger), for wa-
ter (thirst), for warmth or cold, for sex, and so forth; these are drives involving
specific bodily needs. We are also informed of more general need states involv-
ing primary affects, such as happiness, sadness, fear, and anger.
Affect is defined formally as the direct knowledge-by-acquaintance of feelings
and desires based on readouts of specifiable neurochemical systems evolved by
natural selection as phylogenetic adaptations functioning to inform the organism
of bodily events important in self-regulation (Buck, 1985, 1994a). Affects are
special-purpose, gene-based, neurochemical readouts. The subjective phenome-
nal reality of affect is self-evident and is experienced directly and immediately.
Also, affects are always present: A constant readout of feelings and desires is
available at all times. We can always turn our attention to "pick up" how hun-
gry, or thirsty, or warm we are and also how happy, sad, or angry. We tend spon-
taneously to notice this information only when it is strong or sudden, but, like
the feel of our shoes on our feet, it is always with us. Relatively strong affects
associated with specific elicitors are typically termed emotions as compared with
moods, which last longer and are not so associated with specific elicitors (Ek-
man & Davidson, 1994).
Affective and rational cognition

Tucker's distinction (1981) between syncretic and analytic cognition is related
to, but not identical with, the knowledge-by-acquaintance versus knowledge-by-

description distinction. Knowledge-by-acquaintance is syncretic cognition: hot,
holistic, direct, immediate, and self-evident raw acquaintance. In contrast, much
but not all knowledge-by-description is analytic cognition: cold, sequential, and
linear information processing (an exception involves spatial knowledge-by-de-
scription). Combining Tucker's conceptualization (1981) with the present one,
we may say that affective cognition is syncretic and based on special-purpose
systems, while rational cognition is analytic and based on general-purpose sys-
tems (Buck, 1985; Buck & Chaudhuri, 1994; Chaudhuri & Buck, 1995).
The Interaction of Affective and Rational Cognition
Biologically based primes are considered to be special-purpose systems arranged

in a hierarchy in which the interaction with general-purpose systems becomes
more important as one goes up the hierarchy (Buck, 1985). The simplest primes
are reflexes where the response is wholly "hard wired" and innate, with virtually
no flexibility. At the next position on the hierarchy are fixed action patterns, or
instincts, which are quite inflexible when examined closely: One cannot teach
salmon to change their migratory behavior. The next level of the primes does,
however, involve flexibility. Drives involve specific bodily needs that are sig-
naled to the organism by affects: desires like hunger and thirst that function to
activate and direct behavior so that the organism explores its surroundings to
search out and learn to find relevant resources. The next level of the hierarchyzyxwvuts
does not involve specific needs: The primary affects signal a bodily state but do
not influence behavior directly. The individual knows that he or she is happy or
angry and may or may not know why; but no specific behaviors are activated.
Instead, the affects function to facilitate flexibility and choice among alternative
behaviors: The individual has a choice about what to do, and if, for example,
anger is felt toward a large person or a small person, the behavior will be
different.
As one proceeds up the hierarchy from reflexes to instincts, to drives, to af-
fects, the interaction between special-purpose and general-purpose systems in-
creasingly favors the latter. The dimension presented in the upper section of Fig-
ure 2.1 arguably more accurately reflects the relationship between affect and
reason than does the more usual categorical distinction between "emotion" and
"cognition." Also, other phenomena may be usefully placed on this dimension.
For example, the dimension mirrors the phylogenetic scale, with simple crea-
tures' behavior (ants, bees) being mostly a matter of reflexes and creatures with
significant analytic-cognitive capacities being at the other extreme. The pro-
gressive evolution of learning abilities that confer increased behavioral plastic-
ity has been termed anagenesis (Gottleib, 1984). The developmental scale may
also be represented, with the more hard-wired infant at the left and the adult at
Figure 2.1. (Upper) The interaction of affective and rational cognition. *Ryle's "ghost
in the machine" (1949). (Lower) The hierarchy of knowledge. See text for description.
49
the right. Finally, the dimension can represent the evolution of the nervous sys-
tem, with functions served by more "primitive" structures to the left and to the
right increasingly complex functions based on brain stem, midbrain, paleocorti-
cal, and neocortical processing.
Levels of Knowledge
A hierarchy of knowledge
The relationship between affect and reason can also be presented in terms of
three levels of knowledge, which is illustrated in the lower section of Figure 2.1.
The most fundamental sort of knowledge is Gibson's awareness (1966) consti-
tuting knowledge-by-acquaintance: Thus we have an immediate acquaintance
with the external physical environment (terrestrial awareness), of other organ-
isms (social awareness), and of oneself (self/bodily awareness). The latter in-
cludes the affects. All living creatures, even the simplest, manifest this basic
awareness: In this sense it is similar to Aristotle's "vegetative soul." Knowledge-
by-description is termed cognizance, and Figure 2.1 shows three levels of cog-
nizance: associative classical conditioning, goal-directed instrumental learning,
and higher order cognitive processing. These progressively complex sorts of
learning came into existence successively over the course of evolution, and they
conferred progressively greater behavioral flexibility. Knowledge about the en-
vironment is terrestrial cognizance, knowledge about others is social cognizance,
and knowledge about the self, including the affects, is self/body cognizance. Such
representational knowledge is characteristic both of human beings and other an-
imals and is perhaps analogous to Aristotle's "sensitive soul." The level of knowl-
edge that differentiates human beings and nonhuman animals involves language
(Buck, 1994b): Arguably linguistic competence is also what distinguishes Aris-
totle's "rational soul." Linguistic knowledge might be termed understanding,
yielding terrestrial understanding, social understanding, and self and body un-
derstanding. Self-understanding involves a system of rules that is structured by
learning, cognition, and language over the life of the individual, including rules
about the experience and expression of affects.
The role of language

These formal rules constitute a system of behavior control that allows human
behavior to come under the influence of factors outside the experience of the in-
dividual organism. All other creatures are constrained by their own individual
experience during development. They can never escape their own experience no
matter how powerful their higher order cognitive processes. Human beings, in
contrast, can be informed via language by the experiences of those long gone
and can imagine events that never have been and indeed never could be experi-
enced, such as counting the number of angels standing on the head of a pin or
falling into a black hole. This perhaps is the origin of an essential dualism in the
human species apart from the mind-body issue. Language imparts to human be-
havior a formal, logical structure that does not exist in nonhuman animals.
Whereas the forces of natural selection have shaped animal behavior, human be-
havior is influenced as well by formal, linguistically structured, and socially con-
structed social rules. This formal linguistic influence is perhaps in fact analogous
in some ways to Ryle's "ghost in the machine" (Buck, 1994b). Specifically, lan-
guage competence involves principles for organizing behavior that are absent in
nonhuman animals.
Consciousness
Consciousness is represented in Figure 2.1 as ranging from the raw knowl-

edge-by-acquaintance of simple creatures, through the addition of representa-
tional knowledge-by-description, to human linguistic understanding. An as-
sumption here is that consciousness is an emergent function of raw Gibsonian
awareness; another is that earlier forms of nonconscious awareness gradually
evolved into consciousness but that the earlier forms persist in complex crea-
tures. For example, Panksepp (1994a) has cited evidence that the dream state as-
sociated with REM sleep may reflect the functioning of an ancient arousal mech-
anism associated with emotion.
LeDoux and Panksepp have expressed different but perhaps compatible views
regarding emotion and consciousness. LeDoux (1994b) suggested that there is
one mechanism of consciousness that is usually filled with the ordinary concerns
of daily life, with the capacity to be directed toward objects of interest. When a
threatening object is encountered, the emotion network associated with fear takes
over, directing consciousness to relevant objects. Panksepp, in comparison, as-
sociated different sorts of emotional consciousness with different neural systems.
He noted that "there seem to be as many distinct internally experienced affec-
tive states as there are basic motivational and emotional systems of the brain"
(Panksepp, 1994b, p. 396) and suggested that "all mammals probably experience
essentially similar types of basic motivational and emotional feeling states" (p.
399).
It is illuminating to apply these ideas to the example of an emotional situation
suggested by Scherer (personal communication, 1996): losing one's luggage at
the airport. Typically, at the airport one is filled with ordinary concerns, but if
one's baggage is lost attention is directed to coping processes that can involve a
variety of affects. One might consider ordinary functioning to be on the right
side of the affect-reason model in Figure 2.1 and that losing one's luggage would
tend to move functioning to the left, with an increase in the relative ratio of af-
fective to rational functioning. To take the example further, if one loses one's
child at the airport, the ratio of affective functioning might increase rather more
and perhaps particularly involve basic physiological systems associated with

panic (Panksepp, 1982). Furthermore, if one loses one's engines at the airport,
the resulting response might be even more "irrational" and physiologically based.
Finally, if the child is found or the emergency landing is made successfully, the
relief and joy experienced may similarly overwhelm rational considerations.
SUMMARY
A guiding thesis of the chapter is that a greater scientific understanding of that

most "subjective" of phenomena, emotion, can contribute to understanding more
general problems of conscious experience: that a well-grounded and valid con-
ceptualization of emotional knowledge is crucial to understanding the relation
between the mind and the brain. The chapter has discussed the history of philo-
sophical discussions of the epistemological status of public and private events
and suggested that one of the dilemmas with private events is that it is difficult
to construct consensual language to define and describe them. As emotional
events become more public due to technical advances, conceptual advances in
the formalization of language naturally follow. An example is the formalization
of the concept of "cognition" from LeDoux's research. In this regard, a concep-
tualization of how motivation, emotion, and cognition are related is presented.
A major proposition is that emotion in fact involves a kind of cognition, a kind
of knowledge. Analytic "rational" versus syncretic "affective" knowledge are dis-
tinguished and related to three levels corresponding roughly with Aristotle's three
grades of soul: direct, "raw" acquaintance, or awareness; representational knowl-
edge about knowledge, or cognizance; and formal linguistic knowledge, or un-
derstanding. These levels can be observed in knowledge of the external world
as well as in emotional knowledge and can be associated with levels of neural
functioning in the brain, from subcortical systems associated with fast but crude
processing to the more accurate, precise, and detailed processing associated with
cortical systems.
As for the Cartesian impasse? Perhaps eventually human language and un-
derstanding will bridge the gap, but it may involve a reconceptualization of the
basic nature of physical reality (see Hameroff & Penrose, 1996).
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3
Anatomy and Physiology of Human Emotion:
Vertical Integration of Brain Stem, Limbic, and
Cortical Systems
DON M. TUCKER, DOUGLAS DERRYBERRY,

AND PHAN LUU
The neural organization of human emotion spans multiple levels of the brain,
from the elementary adaptive reflexes of the lower brain stem, to the complex
visceral and somatic integration of the hypothalamus and thalamus, to the con-
trol of memory and cognition in corticolimbic networks. At each level, there are
implications not only for the experience and expression of emotion but also for
the effective motivation of behavior.
At the level of the pontine brain stem, for example, there are neural represen-
tations of elementary patterns of laughing and crying. These emotional displays
become disinhibited when lesions disrupt the fiber tracts that mediate limbic and
cortical modulation of the brain stem responses (Rinn, 1984). Anencephalic in-
fants, born with only a brain stem, show well-organized facial displays of plea-
sure and distress (Buck, 1988). At the pontine level, we also find critical moti-
vational mechanisms in the nuclei of the ascending monoamine projection
systems that regulate arousal and alertness according to both internal states and
environmental events (Bloom, 1988). The challenge for a neuropsychology of
emotion is to explain how the elementary levels of the neuraxis are coordinated
with higher cortical systems to control behavior adaptively.
In this chapter, we review the basic outlines of the anatomy and physiology
of human emotion, describing the multiple levels of emotional control that have
resulted from the progressive elaborations of the mesencephalic, diencephalic,
56
Anatomy and Physiology of Human Emotion 57
and telencephalic levels of visceral, reflexive, and behavioral organization in ver-

tebrate evolution. We emphasize the need to understand vertical integration: how
these levels coalesce effectively. Two principles may help with this problem of
understanding vertical integration. The first principle is Jacksonian hierarchic in-
tegration through inhibitory control, through which fixed-action lower circuits
are subordinated to the representational flexibility of higher networks. The sec-
ond, and related, principle is encephalization, through which higher, general-
purpose brain networks take on the functions formerly served by lower, fixed-
action circuits. By sketching the outlines of all of the major emotion control cir-
cuits of the mammalian brain, and then considering these in light of the complex
psychological qualities of human emotion, we attempt to formulate more clearly,
even if we cannot answer satisfactorily, the critical question of vertical integra-
tion of human brain systems.
OVERVIEW OF EVOLUTIONARY NEUROANATOMY
The hierarchic architecture of the human brain can be understood through a

developmental-evolutionary analysis. From the perspective of engineering or
computer science, the human brain presents a convoluted and confusing circuit
architecture. This architecture makes sense only when it is recognized to be the
end point of the progressive differentiation of the brain in vertebrate evolution.
Given the requirement for continuous functioning of each generation, the foun-
dation circuitry remained in place, and new structures were differentiated to mod-
ify, rather than replace, the primordial adaptive mechanisms. The major episodes
of functional transformation were associated with new structures of nerve net-
work anatomy elaborated at the anterior end of the neural tube. These are now
marked by the major divisions of the neuraxis seen in embryogenesis (rhomben-
cephalon, mesencephalon, diencephalon, and telencephalon).
Accounts of human emotion typically emphasize the telencephalic structures
(basal ganglia, limbic circuits, and cortex). It is, however, well-known in clini-
cal neurology that both diencephalic (thalamus, hypothalamus) and mesen-
cephalic (pontine reticular nuclei) structures are critical not only to vegetative
controls and primitive drives but also to the fine regulation of attention and cog-
nition. Many lines of evidence suggest that these subcortical circuits are essen-
tial to the cortical representation of emotional experience and behavior as well.
In this chapter, we briefly outline the major control circuits at each level of the
neuraxis, and we provide examples of how mesencephalic and diencephalic in-
fluences may be integral to human emotion.
The brain stem circuits have been strongly conserved in vertebrate evolution,
with the core nuclei and connections of the amphibian motor system easily traced
in the human brain stem (Sarnat & Netsky, 1974). In contrast, the architecture
of the telencephalon has become highly unique in each avian and mammalian
species. A key insight into mammalian cortical architecture has been achieved
in recent years by the study of the connectivity of the primate cortex (Pandya,
Seltzer, & Barbas, 1988). This research has suggested that the mammalian neo-
cortex evolved from the limbic structures at two points of origin, with the
archicortical base of the cingulate gyrus, parietal lobe, and dorsal frontal lobe
(the spatial or "where" pathway) emergent from the hippocampus and the pale-
ocortical base of the inferior temporal and orbital frontal lobe (the object or
"what" pathway) emergent from primitive olfactory cortex. A theoretical chal-
lenge, thus far unmet, is to determine whether there are unique emotional and
motivational properties of these limbic divisions that are integral to their
mnemonic and cognitive functions. In this chapter, we outline the anatomical or-
ganization of the dorsal and ventral corticolimbic networks, and we raise the
question of the differing motivational and emotional functions of these divisions
of the cortex.
The human brain has a massive frontal cortex and functionally differentiated
cerebral hemispheres. As other chapters in this volume illustrate, these cortical
features have been primary targets for theorizing on the uniqueness of human
cognition and emotion. In the present chapter, we emphasize that the study of
neuroanatomy and neurophysiology not only points out the evolved hierarchy of
the human brain; it leads directly to the question of how the flexible operations
of the human cortex have come to coexist with the homeostatic drives, arousal
mechanisms, and adaptive reflexes of the limbic structures, striatum, and brain
stem.
We address this question with two key classic principles of brain function.
These emerged from the developmental-evolutionary analysis of the nineteenth
century that is again popular in biology (Pennisi & Roush, 1997). The first is
Hughlings Jackson's principle of hierarchic integration through inhibitory con-
trol (Jackson, 1879). Along with his contemporaries, Jackson was impressed by
the evolutionary order in the anatomy of the brain, which is traced by the pro-
gressive differentiation in embryogenesis. Observing that brain stem reflexes dis-
appear as the infant matures, but then reappear following cortical lesions, Jack-
son proposed that the higher (e.g., telencephalic) brain structures evolved to
extend, inhibit, and modulate, rather than to replace, the earlier (e.g., mesen-
cephalic) functional systems. Only in rare instances (e.g., the pyramidal motor
tract) does a higher brain structure actually replace or bypass lower structures.
From this perspective, we may better understand the various forms of disin-
hibitory psychopathology seen in humans with brain lesions. We may also un-
derstand how complex patterns of human emotional experience and behavior are
the composite of hierarchic, vertical integration, through which cortical repre-
sentation networks are regulated by limbic and brain stem control mechanisms.
The second principle is encephalization. It is complementary to Jacksonian hi-

erarchic integration in emphasizing the increasing functional dominance of higher
systems with increasing complexity in the phylogenetic order. Encephalization
is the evolutionary mechanism through which special-purpose controls in the pe-
riphery (e.g., lateral inhibition in the avian retina) are taken over by general-
purpose controls in the central nervous system (e.g., lateral inhibition in the mam-
malian thalamus). A principle such as this is essential to explain how human
emotional responses can be so elaborated in time, removed from proximal stim-
uli. From this perspective, the subcortical circuits that were once complete mech-
anisms for evaluating the sensory context and motivating fixed-action patterns
now must support the more extended adaptive processes of the telencephalon.
These are processes of continually integrating past experience, evaluating the sig-
nificance of events while delaying gratification, and planning the future. Com-
pared with the reflexive fixed-action patterns that comprise the motivational sys-
tems of simple vertebrates, the increasing complexity of mammalian emotional
systems can be seen as the continued extension of the brain's representation of
information in space and time.
In the simplest vertebrates, exemplified in surviving species by Amphioxus,
the primitive brain responded reflexively to local stimuli, such as tactile contact
or pain. With the evolution of sense organs for information from "distant" sources,
such as smell or hearing, more complex brain structures, such as the olfactory
cortex and thalamus, evolved the specialized synaptic networks to process dis-
tant information. Sarnat and Netsky (1974) point out that, by processing distant
information in advance of contact, the vertebrates with special senses could af-
ford the increased delay in processing caused by the increased number of synapses
in the higher (e.g., diencephalic) nerve networks. We suggest that the human
brain represents the continuation of this primordial principle, with progressively
greater extension of the reflex arc (stimulus-response complex) in space and time.
The network architecture of the telencephalon shows the limbic structures as
pivotal for connecting the sensory representational networks of the posterior brain
to the action organization networks of the anterior brain. The limbic circuits and
thalamus are also pivotal in funneling the widespread cortical inputs to the key
regulatory systems of the brain stem, which then project broadly to tune the
arousal and motivational state of the entire neuraxis. The evolutionary trend to-
ward organizing perception and behavior according to "distant" information ap-
pears to be extended in the human brain, through memory capacities that allow
continual integration of past experience to anticipate the events of the future.
These memory capacities cannot be understood by a strictly cognitive analysis.
The complex corticolimbic interaction of the massive human cortices is regu-
lated adaptively by motivational and emotional controls of limbic and subcorti-
cal systems.
SUBCORTICAL BASES OF EMOTION
Emotions comprise specialized neurophysiological subsystems that control mo-

tor, autonomic, and sensory processing. For a coherent theory of emotion, it is
necessary to understand how these component subsystems are coordinated by
higher level structures to produce adaptive emotional states. A number of ad-
vances in integrative capacity appear to have accompanied the evolution of mo-
tivational systems within the brain stem and limbic system.
Component Brain Stem Subsystems
The component subsystems arise from cell groups and nuclei located primarily
within the spinal cord and lower brain stem. Many of these cell groups serve ef-
fector functions through their descending influence on peripheral muscles and
organs. Within the caudal medulla, for example, the medial tegmental field con-
trols the axial trunk and head muscles, whereas the more rostral red nucleus con-
trols the distal limb muscles. Other cell groups control specific behaviors such
as chewing, vocalization, facial expressions, eye movements, and locomotion. In
addition to these somatic functions, medullary cell groups regulate various au-
tonomic reflexes. Some regions appear to control sympathetic activity (e.g., the
rostral ventrolateral medulla), whereas others are concerned with parasympathetic
functions (e.g., nucleus ambiguus) (Holstege, Bandler, & Saper, 1996; Loewy &
Spyer, 1990; Van Bockstaele, Pieribone, & Aston-Jones, 1989).
While these effectors control specific behaviors, additional brain stem systems
serve a more general function of adjusting the gain of spinal transmission. These
include descending projections employing serotonin (raphe pallidus and raphe
obscurus), norepinephrine (locus coeruleus), and dopamine (A 11 cell group).
The monoamines' relatively diffuse projections throughout the ventral horn of
the spinal cord appear to be modulatory; that is, they do not activate the mo-
torneurons, but enhance responses to inputs converging from other brain stem
systems. In addition, they inhibit the transmission of sensory information as it
ascends within the dorsal horn, thereby promoting analgesia in stressful situa-
tions. These descending modulatory systems appear to adjust the balance between
motor and sensory processing within the spinal cord (Holstege, 1991; Holstege,
Handler, & Saper, 1996; White et al., 1996).
A third set of brain stem components includes ascending projections to the
forebrain. Traditionally associated with the reticular activating system, these sys-
tems include (among others) norepinephrine (locus coeruleus), serotonin (dorsal
and median raphe), dopamine (ventral tegmental area), and acetylcholine (nu-
cleus basalis) projections. These cell groups appear responsive to emotional stim-
uli, and their target effects are primarily modulatory (i.e., facilitating or attenu-
ating converging sensory information). Such effects are consistent with recent
studies showing how emotional states regulate attention (Niedenthal & Kitayama,
1993). It has been suggested, for example, that during positive states noradren-
ergic projections may promote an expansive, present-centered state of cortical
processing. In contrast, negative states may recruit dopaminergic projections to
promote a more focused, future-oriented attentional state (Tucker & Williamson,
1984).
Integrative Brain Stem Mechanisms
When viewed as a whole, the brain stem consists of discrete subsystems serving
somatic, autonomic, and modulatory components. To produce emotional behav-
iors, however, these components must be coordinated by higher level structures.
Although such coordination is facilitated by limbic and cortical projections, its
primitive basis can be found within the brain stem itself. Some of these integra-
tive mechanisms are relatively specific. For example, the nucleus paragiganto-
cellularis provides the main source of sympathetic drive within the organs of the
autonomic nervous system while also providing the most potent afferent input to
the locus coeruleus. Such projections suggest a mechanism for coordinating the
ascending noradrenergic influence on the forebrain with sympathetic tone
throughout the body (Aston-Jones, Chiang, & Alexinsky, 1991; Van Bockstaele,
Pieribone, & Aston-Jones, 1989).
More rostral brain stem structures appear to provide more elaborate integra-
tive influences. The midbrain periaqueductal gray (PAG) possesses descending
projections to somatic, autonomic, and modulatory cell groups, allowing it to co-
ordinate their activities in patterns related to general motivational states. Recent
findings indicate that the PAG is organized into columns of cells, with each col-
umn related to a motivational pattern. The lateral column organizes active forms
of defensive behavior and appears particularly responsive to superficial pain.
Stimulation of the intermediate region of the lateral column elicits confronta-
tional defensive behavior (i.e., defensive aggression) and blood flow to the face,
whereas stimulation of the caudal region of the lateral column elicits flight be-
havior and increased blood flow to the limbs. Both of these defensive patterns
are accompanied by increased heart rate and a nonopioid analgesia. In contrast,
the adjacent ventrolateral column orchestrates a more passive strategy in response
to deep pain. This pattern involves a cessation of ongoing motor activity, hy-
poreactivity, hypotension, decreased heart rate, and opioid-mediated analgesia.
In its primitive form, the passive pattern may serve defensive purposes (e.g., play-
ing dead), or it may serve recuperative functions following serious injury (Ban-
dler & Keay, 1996; Bandler & Shipley, 1994). Future studies of the PAG promise
a better understanding of some of the brain's most basic emotional functions in
terms of both their identity (e.g., defensive, recuperative, and sexual) and their
patterned organization.
Integrative Limbic Influences
The more recently evolved limbic structures that surround the brain stem serve
a number of functions central to emotion and cognition. In terms of emotion,
these circuits provide higher levels of integrative control over the brain stem. At
the diencephalic level, the hypothalamic nuclei receive extensive exteroceptive
and interoceptive sensory information and innervate multiple brain stem struc-
tures. Hypothalamic projections to the motor and autonomic pools of the lower
brain stem allow for a fine tuning of homeostatic functions based on a detailed,
integrative monitoring of ongoing metabolic conditions (Swanson, 1987). By
means of additional projections to the pituitary, the hypothalamus (paraventric-
ular nucleus) can coordinate peripheral endocrine activity in light of ongoing so-
matic, autonomic, and modulatory activity (Loewy & Spyer, 1990). In addition,
hypothalamic projections appear capable of regulating brain stem integrative
mechanisms. For example, the ventromedial hypothalamus exerts a descending
inhibitory influence on cell groups within the PAG that are responsible for de-
fensive aggression. It has been suggested that such suppression of brain stem ag-
gressive tendencies has been crucial in the evolution of prosocial behaviors in-
volving trust, play, and affection (Panksepp, 1986).
Hypothalamic projections also regulate the fearful forms of defense organized
within the brain stem. Gray and McNaughton (1996) suggested that the hypo-
thalamus and PAG function together, along with the amygdala, as part of a dis-
tributed fight-flight system. The PAG mobilizes defensive behavior given prox-
imal sources of threat (e.g., pain or a predator) when there is little time for
analysis. If the threat is very close and allows no avenue of escape, then fight-
ing is elicited, but, given more distance or more room for escape, undirected
flight is elicited. In contrast, the ventromedial hypothalamus mobilizes defense
in situations involving more distal threats and more time for sensory analysis.
The hypothalamic organization takes the form of directed escape behavior, and
it is coordinated by regulating the PAG and recruiting additional brain stem re-
gions involved in orientation (superior colliculus) and locomotion (cuneiform
nucleus) functions. It is worth emphasizing that these primitive forms of de-
fensive behavior are based on threats that are physically present and temporally
urgent. Several theorists have suggested that they give rise to emotional states
of panic, which are distinct from the anticipatory states of anxiety orchestrated
by higher limbic and cortical circuitry (Graeff, 1991; Gray & McNaughton,
1996). The evolutionary progression in motivation can be seen as moving from
reflexive responses to systems that engage defensive or other adaptive behav-
ior in the face of proximal stimuli to systems that maintain an emotional state
to bias the organization of behavior appropriately (e.g., a threatened posture)

over extended intervals of time.
Limbic Anticipatory Functions
More anticipatory emotional capacities appear to have evolved along with two
telencephalic limbic structures, the amygdala and hippocampus. Both of these
structures have extensive descending inputs to the hypothalamus, and the amyg-
dala also projects throughout the brain stem. Although the amygdala is a com-
plex structure with multiple nuclei, recent evidence suggests a crucial role in as-
sociating exteroceptive information with information concerning rewarding and
aversive outcomes. Such learned associations allow the amygdala to organize
emotional activity in light of potential rather than actual events. For example,
when a rat is exposed to an auditory tone that signals an impending shock, the
auditory information is delivered to the amygdala's lateral nucleus. The amyg-
dala can respond based on relatively crude input delivered from the thalamus or
on more highly processed information from the cortex. In either case, an imme-
diate conditioned fear response is initiated by projections from the lateral nucleus
to the basal nucleus (which projects to the ventromedial hypothalamus) and the
central nucleus (which projects to the brain stem) (Davis, 1992; Petrovich, Risold,
& Swanson, 1996; Savander et al., 1995).
Although it is supported by activity within the PAG and the hypothalamus,
the amygdaloid fear response differs from the more primitive forms of ex-
plosive and directed escape. In Gray and McNaughton's terms (1996), the
amygdala facilitates anticipatory, active avoidance. Thus, the response inte-
grates a more flexible set of response options in relation to a potential, im-
pending danger. Because these options depend on complex, distal sensory in-
formation, the amygdala must be crucially involved in coordinating response
and attentional functions. In locomotion, for example, the animal must em-
ploy attention to seek out sources of threat (to avoid) and safety (to approach).
Such flexibility is based on the amygdala's control over more ballistic brain
stem and hypothalamic functions. In addition, projections to response-
programming mechanisms within the basal ganglia and frontal cortex allow a
finer tuning of selected response options. Furthermore, the amygdala projects
(together with the PAG and hypothalamus) to the brain stem's ventral tegmen-
tal area, allowing it to adjust the focused attentional state related to the as-
cending dopaminergic projections. Finally, the amygdala projects extensively
on the sensory and association areas within the posterior cortex, allowing a
more direct modulation of the sensory information that is converging on the
response systems. Thus, the amygdala's integrative capacities are quite ex-
tensive, coordinating somatic, autonomic, and sensory processing within the
brain stem, limbic system, and cortex.
A final telencephalic structure, the hippocampus, provides a mix of subcorti-

cal and cortical functions. In addition to its well-known role in spatial process-
ing (Nadel, 1991), recent findings seem to be converging on a general role of the
hippocampus in memory (Eichenbaum, Otto, & Cohen, 1994). In contrast to the
amygdala, which is involved in associative memory processes involving discrete
objects, the hippocampus appears more concerned with memory for contextual
and relational information. Various researchers have described this capacity in
terms such as working, declarative, and configural memory as opposed to ref-
erence, procedural, and associative memory. A simple example involves the con-
ditioning of a fear reaction to background contextual information, apart from the
conditioned stimulus itself (LeDoux, 1995). Consistent with these functions, it
has been suggested that the hippocampus contributes to defensive behavior by
providing contextual information that complements the object information
processed within the amygdala (LeDoux, 1996). This allows another type of an-
ticipatory emotional function based on contextual properties of the environment
rather than on discrete threatening objects.
The hippocampus has also been viewed as central to a behavioral inhibition sys-
tem (Gray & McNaughton, 1996), which provides a fourth level to the hierarchy
extending from the PAG to the hypothalamus to the amygdala. Gray & McNaughton
(1996) suggest that the hippocampal formation contributes to defensive behavior
when active avoidance is in conflict with an equally strong approach tendency.
Specifically, the behavioral inhibition system performs a conflict resolution func-
tion by determining which of the competing tendencies is most appropriate to the
current (often spatial) context and suppressing the inappropriate options (and mem-
ories). This capacity relies on hippocampal projections to the fear-related circuits
within the amygdala and hypothalamus, to response programming mechanisms of
the basal ganglia, and to association and motor areas of the cortex. These outputs
orchestrate a complex form of anticipatory anxiety, involving extensive contextual
processing, competing response options, and an emphasis on inhibition.
In summary, subcortical emotional functions are carried out through a hierar-
chy of projections that integrate multiple motor, autonomic, modulatory, and en-
docrine subsystems. Although we have emphasized the descending influences,
emotional states also coordinate many ascending subsystems, such as the mas-
sive forebrain projections from the locus coeruleus, ventral tegmental area, hy-
pothalamus, amygdala, and hippocampus. These combined descending and as-
cending influences suggest that emotional states facilitate a vertical integration
of processing systems across the brain stem, limbic system, and cortex. As these
systems evolved, the higher level structures enabled flexible and integrative mo-
tivational systems based on increasingly distal and anticipatory sensory process-
ing. This progression continued with the evolution of mammalian cortical
networks.
ANATOMY AND PHYSIOLOGY OF CORTICAL SYSTEMS
In reptiles and amphibians the cortex is only incipient, with a highly undiffer-
entiated organization. Based on his comparative anatomical studies, Herrick
(1948) proposed that cortical morphogenesis is shaped by adaptation of cortical
regions to subcortical inputs. The primitive pallium (hemisphere) can be divided
into two fields: the paleocortex (olfactory) and the archicortex (hippocampal).
Based on modern anatomical findings and on a consideration of the subcortical
and brain stem connections, we can use Herrick's reasoning to see how the two
fields of the pallium differentiated under the influence of unique subcortical
inputs.
Archicortical and Paleocortical Routes of Corticolimbic Evolution
Evidence for the archicortical and Paleocortical routes of corticolimbic evolution

may be traced in Nauta's pivotal study (1964) of the anatomy of the primate
frontal lobe. When studying the efferent connections of the prefrontal cortex,
Nauta noticed that it was organized into two routes. One route originates from
the medial prefrontal areas and travels via the cingulum bundle and terminates
in the medial temporal lobe (subiculum and entorhinal areas). The second route
(the uncinate faciculus) connects the orbitofrontal cortex with the temporal pole,
insula, and amygdaloid complex. Nauta remarked that the observed duality in
the organization of prefrontal efferents may reflect something fundamental about
the organization of the brain.
The anatomical separations of dorsal and ventral cortical systems led Sanides
(1970) to propose that the cerebral cortex evolved along two lines of differenti-
ation, one from the primitive paleocortex and the other from the archicortex. The
archicortex gave rise to cortices on the mediodorsal surface, and the paleocortex
gave rise to cortices on the ventrolateral surface of each hemisphere (Pandya,
Seltzer, & Barbas, 1988; Sanides, 1970). For example, the hippocampus gives
rise to the cingulate cortex on the medial surface of the cerebral hemisphere. In
the frontal lobe, the anterior cingulate gives rise to cortex on the medial (such
as the supplementary motor area) and dorsolateral surface. In contrast, the pale-
ocortex gave rise to the orbitofrontal cortex and then to the ventrolateral frontal
region. In monkeys, the principal sulcus is where the two trends converge on the
lateral surface; in humans, it is the inferior frontal sulcus. Sanides (1970) noted
that the connectional findings by Nauta (1964) may reflect the differential orga-
nization of the cerebral cortex according to these two trends.
More recent evidence has verified the initial work of Sanides and Nauta. Based
on extensive studies detailing the architectonic and architecture of cortical con-
nections in primates, Pandya, Seltzer, and Barbas (1988) found that cortices and
structures within each trend show a preferential pattern of connectivity. Similar

to the pattern of connections reported by Nauta, Barbas, and colleagues found
that the hippocampus, although projecting to both trends within the prefrontal ar-
eas, sends denser projections to the mediodorsal prefrontal cortex (Barbas & Blatt,
1995) and that the amygdala's projections to the prefrontal limbic cortex were
densest at the caudal orbitofrontal regions (Barbas & De Olmos, 1990).
The separation of the archicortical (dorsal) and paleocortical (ventral) trends
is not limited to connections between limbic structures with the prefrontal cor-
tex. It appears that the dual trends represent a fundamental way in which the
brain is organized; this pattern holds for both motor areas (Barbas & Pandya,
1986) and visual areas (Barbas, 1988). For example, the ventrolateral visual cor-
tices (derived from the paleocortex), which are involved in the processing of ob-
ject information, are preferentially connected with the ventrolateral and basal pre-
frontal cortex, and the medial and dorsolateral visual cortices, which are involved
in visuospatial processing, are preferentially connected with the medial and dor-
solateral prefrontal cortex (Barbas, 1988, 1995). This pattern of connections with
the visual areas no doubt contributes to the spatial functions of the mediodorsal
prefrontal cortex (Fuster, 1989; Goldman-Rakic, Funahashi, & Bruce, 1990) and
the object functions of the ventral and lateral prefrontal cortex (Wilson,
O'Scalaidhe, & Goldman-Rakic, 1993).
Additionally, Pandya, Seltzer, and Barbas (1988a) and Pandya and Yeterian
(1990) noted that corticocortical connections reflect the evolutionary progression
of the cortex. That is, the pattern of cortical projections follows the sequence of
cortical differentiation such that a given area has dense connections with its pre-
cursor and successor and lesser connections with evolutionarily distant regions.
More recent areas send projections to older areas via the supragranular layers
and receive reciprocal projections to layer I. The older areas receive projections
in layer IV and send efferents from their infragranular layers. The functional sig-
nificance of this architecture is that sensory areas that receive extensively
processed information are densely connected with limbic centers involved in the
control of motivation and memory. Furthermore, limbic control of information
processing occurs most abundantly in the processing layers of sensory areas in-
volved in complex and holistic information.
Corticolimbic Mechanisms of Memory and Cognition
The clarification of cortical anatomy by Pandya and associates has shown the
patterns of connectivity that must constrain efforts to frame computational mod-
els of memory in neuroanatomical terms (McClelland, McNaughton, & O'Reilly,
1995; Treves & Rolls, 1994). The evolutionary analysis helps to explain why the
limbic system forms the base for both sensory integration and motor organiza-
tion: The cortex evolved by differentiating from limbic structures. This analysis
also explains why corticolimbic pathways are essential to memory functions: It

is the motivationally significant information that gains consolidation in memory
(Kornhuber, 1973). The adaptive significance of sensory information—the ex-
tent to which it resonates with core concepts of needs and values—is what de-
termines whether that information will be allocated processing capacity in a lim-
ited memory store.
Given the anatomical distinction between archicortical and paleocortical divi-
sions of the cortex, it may be that the dorsal and ventral trends operate under dif-
ferent memory mechanisms, perhaps with different motivational biases. Mishkin
and colleagues (see Bachevalier & Mishkin, 1986; Mishkin, 1982; Mishkin &
Murray, 1994; Mishkin & Phillips, 1990) have outlined two memory circuits.
One circuit consists of the mediodorsal nucleus of the thalamus, the amygdala,
and the ventromedial aspects of the prefrontal lobe. We refer to this circuit as
the ventral circuit to emphasize the paleocortical components within this system.
The second circuit involves the anterior nucleus of the thalamus, the hippocam-
pus, and the mediodorsal prefrontal lobe (cingulate). We refer to this circuit as
the dorsal circuit to emphasize the cingulate cortex and the hippocampus, both
belonging to the archicortical trend.
As described above, the hippocampus and the dorsal circuit may be important
not only to spatial memory but also to memory for context (Nadel, 1992; Nadel
& Moscovitch, 1997). Based on findings that the hippocampus is important to
the processing and encoding of nonreinforced stimuli, Pribram (1991) suggested
that the hippocampus supports the contextual representation in which behaviors
occur. Similarly, Nadel (1992) believes that the hippocampal memory system
emphasizes the unique aspects of an event to be remembered. Thus, memory
supported by the hippocampal system would resemble a key aspect of episodic
memory.
As suggested by the studies of lesions to the inferotemporal pathway (Unger-
leider & Mishkin, 1982), the ventral memory circuit is important to memory for
objects rather than for spatial locations. Nadel has suggested that the ventral cir-
cuit's contribution may be generalized to categorical memory, that is, memory
based on identity of objects (Nadel, 1992). Consistent with a context versus cat-
egory distinction, Gaff an (1994) found that lesions to the fornix and perirhinal
regions (dorsal circuit) result in recognition memory for complex scenes, whereas
lesions to the amygdala (ventral circuit) result in deficits for food preference
learning.
Although the theoretical analysis of corticolimbic function has yet to take ad-
vantage of the new insights of connectional anatomy, there have been sugges-
tions that the motivational functions of limbic circuitry may be considered in
neuropsychological models of memory. Several lines of evidence show that cor-
ticolimbic pathways must be intact for memory consolidation to occur (Squire,
1986). Because patients with hippocampal and medial temporal damage may be
impaired in new learning, but not in access to previously learned material, the
assumption has been that the neocortex is adequate for storage and retrieval of
memory once the limbic structures and paralimbic cortices have participated in
the consolidation process (Squire, 1986).
Nadel and Moskovitch (1997) have recently reviewed the literature on human
amnesia and have drawn conclusions that may point to the importance of moti-
vational factors in memory access. They point out that the evidence is actually
fairly weak for full access to memories laid down before the medial temporal in-
sult, particularly if memory is tested for autobiographical information rather than
for general semantic knowledge. Therefore, intact limbic structures may be im-
portant to retrieval as well as to consolidation of memory. The fact that the lim-
bic contribution is particularly important to accessing autobiographical memory
is consistent with the view that the limbic system is important to evaluating the
emotional and motivational significance of information to be retained in mem-
ory (Kornhuber, 1973).
Descending Projections for Emotional Control
In addition to showing how subcortical controls are brought to bear on the cog-
nitive functions of the cortex, the evidence on the anatomy of corticolimbic net-
works provides important insights into the cortical influences on subcortical sys-
tems. Nauta's initial delineation (1964) of the dorsal and ventral pathways of the
frontal lobe showed the connections through which the frontal lobe can modu-
late limbic function, and these pathways have been confirmed by recent anatom-
ical studies (Barbas & Pandya, 1986). Two carefully studied examples, the star-
tle response and primate emotional vocalizations, illustrate the role of cortical
and limbic networks in regulating brain stem emotional systems.
The startle response shows how emotional states modulate brain stem func-
tion in humans as well as rodents and carnivores (Lang, Bradley, & Cuthbert,
1990; Vrana, Spence, & Lang, 1988). The startle response is a simple reflex me-
diated by a brain stem circuit of five synapses (auditory nerve, ventral cochlear
nucleus, nuclei of the lateral lemniscus, nucleus reticularus pontus caudallis, and
spinal interneuron) plus the neuromuscular junction. This circuit is modulated by
higher control from limbic structures, particularly the amygdala (Davis, Hitch-
cock, & Rosen, 1987). In humans, complex emotional states, engaging wide-
spread cortical networks (such as when subjects view photographic slides of nudes
or mutilated bodies), result in inhibition of the startle response for pleasant states
and in facilitation for aversive states (Lang, Bradley, & Cuthbert, 1990; Vrana,
Spence, & Lang, 1988). The implication is that the cognitive representations of
the cortex are associated with an appropriate adaptive set established across mul-
tiple levels of the neural hierarchy. Although startle may not be a significant mo-
tivational mechanism in humans, the orderly modulation of this reflex illustrates
the role of emotional states in linking a variety of systems, including postural,

motor, sensory, and visceral, up and down the neuraxis.
The differential roles of cortical and limbic influences in regulating emotional
systems was particularly clear in Ploog's investigations (1981) of the monkey's
emotional vocalizations. Ploog showed that the monkey's calls are organized at
the most basic level in discrete motor nuclei of the lower brain stem. At the next
level, these nuclei are subordinated to the species-specific patterned motor se-
quences that are organized in the midbrain. For the motor sequences to show
modulation by the animal's current emotional state, the contributions of the lim-
bic structures (amygdala and hippocampus) are required. The corticolimbic (cin-
gulate) control of this hierarchy comes into play for what Ploog calls "voluntary
call initiation" in which the limbic-brain stem hierarchy is recruited in service
of more complex goal-oriented behavior. At the final level, the neocortical con-
trol becomes important for "voluntary call formation" in which frontal and
motor cortices bypass the midbrain pattern generators to articulate specific
vocalizations.
Ploog (1992) suggests that an elaboration of this neocortical control of vocal-
ization may underlie human language capacity. At the same time, he points out
that the human brain has undergone expansion of structures such as anterior thal-
amic nuclei that link frontal cortex to the limbic system. Ploog's analysis is con-
sistent with the observations of disinhibited emotional displays in humans with
cortical lesions (Brodal, 1969; Monrad-Krohn, 1947). Human vocalizations can
thus be seen to involve not only the direct cortex-to-brain stem pyramidal path-
ways but also the hierarchy of pathways that integrate limbic with diencephalic
and lower brain stem control of emotional vocalization.
VERTICAL INTEGRATION OF MOTIVATIONAL AND

EMOTIONAL SYSTEMS
The anatomy and physiology of emotional systems is thus complex, comprising

an evolved hierarchy of control processes. For a neuropsychological theory to
account for the anatomical and physiological evidence, a critical issue is verti-
cal integration, how the control processes are coordinated across the multiple lev-
els of the neuraxis. Fundamentally, human emotion encompasses the primitive
reflexes and homeostatic drives of the vertebrate brain. Vertical integration must
explain how these reflexes and drives can act to shape attention and memory
while at the same time becoming subordinated to more complex processes of
cognitive representation.
In addition to the cortical modulation of subcortical responses, the extensive
memory and cognitive capacities of the human cortex depend on adequate reg-
ulatory control by limbic and brain stem mechanisms. An important task for a
neuropsychological theory of emotion is to explain how subcortical controls have

evolved from direct, reflex-like adaptivity to provide generic support functions,
such as arousal control, significance evaluation, and action motivation, to sup-
port the ongoing, cognitively mediated sensorimotor integration that character-
izes human behavior. We suggest that modern neuroanatomy and neurophysiol-
ogy continue to support Jackson's hierarchic, evolutionary model, specifically as
applied to understanding human motivation and emotion.
Hierarchic Anatomy of Emotion and Memory
Connectivity implies function. Although this has always been the assumption of
the anatomical method, modern connectionist models provide specific examples
of how patterns of connectivity constrain the functional architecture of distrib-
uted networks (McClelland, McNaughton, and O'Reilley, 1995; Rumelhart &
McClelland, 1986). Papez's initial formulation (1937) of a limbic system came
from observations of connectivity, indicated by the propagation of seizures
through the dorsal limbic circuitry. The hierarchic organization of emotional be-
havior was recognized in MacLean's pioneering studies of the limbic system
(e.g., MacLean, 1993; Pribram & MacLean, 1953). Maclean emphasized that the
development of the cingulate cortex in mammals occurred with the appearance
of fundamentally new forms of behavior, including social attachment and play.
We now recognize that these new capacities are essential to support the in-
creasingly extended juvenile period that allows the plasticity of the mammalian
cortex (Tucker, Luu, & Pribram, 1996).
Several lines of evidence suggest that limbic mechanisms are critical to the in-
tegration of motivational controls with the cognitive capacities of human corti-
cal networks. Mesulam (1988) proposes that the ascending cholinergic projec-
tions of the nucleus basalis provide modulatory control over the corticolimbic
interactions in memory consolidation. Studies of the cholinergic projections to
the sensory input pathways of the amygdala show increasingly strong choliner-
gic modulation as the pathways approach the limbic system. Mesulam suggests
that the cholinergic control may be important for gating cortical information ex-
change into and out of the limbic system.
Most of the cortical areas do not, however, project to the nucleus basalis; rather,
it is controlled primarily by the limbic structures and paralimbic cortices. Thus, an
important aspect of the memory architecture of the mammalian cortex shows a fan-
in of control through which the limbic areas respond to the motivational and emo-
tional content of the corticolimbic traffic and determine the feedback to be applied
to the nucleus basalis; the nucleus basalis then projects back in a fan-out pattern
to regulate widespread regions of corticolimbic traffic (Mesulam, 1988).
Because connections between cortical regions and limbic structures are re-
quired for memory consolidation (Squire, 1992), we can look to corticolimbic
physiology for clues to the mechanisms for motivating memory consolidation.

The hippocampus shows a particular affinity for the process of long-term po-
tentiation, a model of Hebbian learning in which afferent input to a neuron re-
sults in a permanent potentiated response if it is associated with simultaneous ac-
tivation of that neuron by another source (Gustafsson & Wigstrom, 1988; Teyler,
1986). The reactivity of limbic structures is shown by the electrophysiological
phenomenon of kindling. Electrical stimulation anywhere in the cortex tends to
elicit responses from the amygdala and hippocampus preferentially. This obser-
vation of limbic excitability in animal studies parallels the tendency of epileptic
seizures to focalize in the medial temporal lobes in humans. In the animal stud-
ies, repeated stimulation may "kindle" increasingly amplified responses from the
limbic structures, propagating throughout the cortex. The eventual result may be
a pathological facilitation of corticolimbic excitability, evidenced by spontaneous
seizures (Dichter & Ayala, 1987).
Long-term potentiation is typically considered to be a model of learning,
whereas kindling is typically considered to be a model of epilepsy. The relevance
of corticolimbic sensitization to general mechanisms of learning and memory is,
however, shown by the finding that kindled seizures can be classically condi-
tioned (Janowsky, Laxer, & Rushmer, 1980). The relevance of motivational con-
trol of corticolimbic excitability has been suggested by evidence of limbic sen-
sitization in both normal and pathological forms of emotional responses
(Harkness & Tucker, in preparation; Sapolsky, 1992; Tucker & Luu, 1999). Hark-
ness and Tucker propose that a traumatic emotional response induces a pattern
of limbic reactivity involving the same electrophysiological and endocrine mech-
anisms as kindling. Thus, subsequent exposure to a traumatic stimulus may elicit
a response that is disproportional to the stimulus unless the sensitization caused
by the traumatic history is appreciated (Harkness & Tucker, in preparation).
Mechanisms of Limbic Drive
A different perspective on the contributions of limbic networks to cortical func-

tion has been provided by studies of emotional disorders in patients with tem-
poral lobe epilepsy. Flor-Henry (1969) observed that, of those epileptics who de-
velop major psychiatric symptoms, patients with a left temporal focus were more
likely to show a schizophreniform disorder, whereas those with a right temporal
focus were more likely to show an affective disorder. A consistent set of obser-
vations, with a more direct parallel with hemispheric psychological functions,
has been gathered in psychometric studies of temporal lobe epileptics by Bear
and Fedio (1977).
Bear and Fedio (1977) used both self-ratings and observer ratings of the pa-
tients and found what appeared to be an exaggeration of the pathological hemi-
sphere's psychological processes. Consistent with Flor-Henry's observations
(1969), the epileptics with right temporal focus showed affective instability and
emotional expressiveness in their behavior, possibly suggesting an exaggeration
of the right hemisphere's role in affective prosody and emotional communica-
tion. As if reflecting an exaggeration of the left hemisphere's verbal cognitive
capacities, the epileptics with left temporal focus were found to show an
"ideative" pattern of traits, with a preoccupation with intellectual, philosophical,
and religious concerns.
The Bear and Fedio (1977) findings were predictably controversial, but they
have been replicated in independent samples (Fedio, 1986; Fedio & Martin,
1983). Although the subsequent findings may seem at first to confirm charac-
terizations of the right hemisphere as emotional and the left hemisphere as non-
emotional, closer inspection shows that the psychological operations of the epilep-
tic hemisphere were charged with emotional significance for the left as well as
the right sides. The left temporal lobe-affected patients were obsessed with the
personal importance of their intellectual concerns, often writing long treatises on
the topics. To explain the exaggerated personal significance associated with the
intellectual as well as the affective behavior, Bear and Fedio proposed that the
epileptic disorder resulted in a "functional hyperconnection" of limbic areas with
the cortex.
These several observations on limbic reactivity may provide a way of under-
standing, in both psychological and neurophysiological terms, how limbic areas
use their privileged connectivity with subcortical control systems to motivate
memory consolidation and therefore cognitive processing. These observations
may also help to integrate the emphasis on vertical integration in the present
chapter with the evidence on hemispheric specialization reviewed in other chap-
ters of this volume (Gainotti, Chapter 9, this volume; Davidson & Henriquez,
Chapter 11 this volume). The massive human cortices provide extensive, but lim-
ited, representational capacity. The selection for a representation to be consoli-
dated within cortical networks is based on the adaptive resonance it recruits within
limbic structures and paralimbic (archi and paleo) cortices. The adaptive reso-
nance may be extended in time, as in ruminations, obsessions, and fantasies. The
linked networks from sensory areas to limbic cortex (Pandya & Yeterian, 1985)
are engaged by this resonance, stabilizing memory representations in a distrib-
uted fashion across the paralimbic and neocortical levels.
As Pandya and associates have pointed out, the "back projections" from lim-
bic toward cortical areas are as extensive as the "forward projections" carrying
sensory data from primary sensory cortex to the intermediate association areas
to paralimbic cortex. In modern psychological theories of perception, the per-
ceptual process is seen as one in which memory and expectations resonate with
and shape the organization of sensory input (Shepard, 1984). Shepard (1984) em-
phasizes the active, constructive role of memory by suggesting that perception
is "hallucination constrained by the sensory data." In the context of the corti-
colimbic architecture for perception, we would add that the resonance is shaped
by inherent motivational constraints incorporated with the representation at the
paralimbic level. Because they are the most densely interconnected of cortical
networks, the paralimbic cortices provide a global, integrative, and yet undiffer-
entiated, mnemonic context for cognition. Given their connectivity to subcorti-
cal controls and their intrinsic excitability, the paralimbic cortices may provide
the motivational drive for evaluating and consolidating significant contents in
memory.
The physiology of motivated perception may thus be seen as a kind of arbi-
tration across layered networks, anchored at the superficial layers by sensory an-
alyzers and energized in the deep layers by a resonance of the information with
a global representation of adaptive need states (Derryberry & Tucker, 1991). Be-
cause the paralimbic representations are the composite of the person's develop-
mental experience, the "limbic drive" structuring perception is formed not
just by immediate homeostatic needs, but by more extended processes of self-
representation. In this manner, the self may be understood as the implicit con-
text of autobiographical memory. In normal personalities, there is an effective
arbitration of perception between limbic drive, with its inherent motivational,
self-referential constraints, and the requirements for maintaining veridical and
complex representations in the neocortex. Judging from the personality disorders
of temporal lobe epileptics, limbic drive occurs not only in the emotionally ex-
pressive right hemisphere but also in the verbal and analytic left hemisphere as
well. We may speculate that the charged intellectualizations of epileptics with
left temporal lobe focus may have their counterparts in disorders in which lim-
bic kindling may be psychopathological rather than neuropathological, such as
in the forced ruminations of the obsessive or the rigid delusions of the paranoid
(Shapiro, 1965). In contrast, excessive limbic drive may take a more affectively
labile form within the right hemisphere, supporting the loose modes of self-
regulation of the histrionic, psychopathic, and impulsive personalities (Tucker,
1981).
Motive Persistence
Although the distorted cognition in emotional disorders may be most easily un-
derstood in terms of temporal-limbic dysfunction, there are more subtle deficits
of motivation that occur with damage to the frontal lobe that result in profound
deficits in life adjustment. Patients with mild frontal lesions may appear entirely
normal during clinical examination and cursory neuropsychological testing. De-
spite the popular "working memory" idea of frontal lobe function, the memory
deficits of these patients are typically not a significant feature of their clinical
presentation (Squire, 1987). Yet within a short time of returning to work and
family life, patients with frontal lesions often experience complete failures of ad-
justment. The problem seems to be not just a memory defect but also an inabil-
ity to motivate ongoing behavior in relation to long-term goals (Lezak, 1983;
Luria, 1973).
The frontal lobe's expansion in human evolution may support a vertical integra-
tion of multiple adaptive systems to allow complex behavior to be organized over
time. The massive cortical networks provide cognitive representational capacity, yet
this capacity is not effective unless it is controlled in relation to the adaptive chal-
lenges that humans must organize over increasingly extended intervals of time. Ex-
tended challenges, such as keeping a job or maintaining a relationship, are the tasks
at which frontal-lesioned patients fail. As recognized in classic formulations, the
frontal cortex mediates between the motivational and emotional representations in
limbic areas and the organization of action in premotor areas (Nauta, 1971; Pribram,
1950). In doing so, the frontal networks are able to integrate functions such as arousal
control that require contributions from lower as well as higher levels of the neuraxis
(Luria & Homskaya, 1970; Yakovlev & Lecours, 1967).
In the extended plasticity of frontal networks through the long human juvenile
period, cortical representations appear to form that mirror not only the percep-
tual operations of the posterior brain but also the regulatory controls of limbic
and subcortical structures. The effect seems to be a kind of encephalization of
vertical integration such that, toward the end of the juvenile period, human frontal
cortical networks may be prepared to take on increasing control of the multiple
levels of the neural hierarchy required for effective self-regulation.
Intrinsic Motivation: The Cognitive Means Become the End
The study of neuroanatomy and neurophysiology thus uncovers many mecha-

nisms of emotion and motivation that humans share with primitive vertebrates.
It also points to structures and mechanisms that are unique to the human brain.
The increasing emphasis on "distant" events, evident in the progression from
mesencephalic to diencephalic controls in primitive vertebrates, can be seen as
a simple principle that continues to describe evolution of motivation in the ex-
ecutive functions of the human frontal lobes.
Although a thorough knowledge of the vertebrate control systems is essential
for understanding human neuropsychology, the human cortex appears to repre-
sent and subsume motivational and emotional processes to an extent unknown
among other mammals. Instead of stereotyped, species-specific motivations, hu-
mans acquire flexible, and highly idiosyncratic, patterns of motivation as neural
plasticity shapes and reshapes the cortical mantle over a 20-year juvenile period.
To allow the extended neural plasticity of massive cortical networks, subcor-
tical control systems appear to have become redirected from reflexive, immedi-
ate influences on behavior to take on the increasingly complex support opera-
tions for the corticolimbic matrix. Thus, the task of arousal control is important
not just to facilitate a reflex but also to facilitate memory consolidation across
distributed cortical networks. The task of detecting the adaptive significance of
a perception is important both to release an endocrine secretion and to code a
sensory pattern for the limbic resonance that excites corticolimbic consolidation.
In many ways, the neurophysiology of human motivation has become en-
cephalized in a way that inverts the relation between cortical and subcortical sys-
tems. Whereas the cortex was initially a device for elementary representation and
memory, supporting the integration between the stimulus and response circuits
in the reflexes of the subcortical control systems, in human evolution the tables
are turned. The support of cortical operations has now become the primary task
of the subcortical systems. Although humans continue to struggle with biologi-
cal needs, there are now many people who are motivated, at least briefly, by in-
tellectual interests. Activities such as curiosity, reasoning, and the search for un-
derstanding are a kind of inversion of the vertebrate control hierarchy. The
corticolimbic networks that once served a subordinate support function for brain
stem adaptive mechanisms have now commandeered the motivational systems to
support cognition as an end in itself.
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4
Neuropsychological Assessment of Emotional
Processing in Brain-Damaged Patients
JOAN C BOROD, MATTHIAS H. TABERT,

CORNELIA SANTSCHI, AND ESTHER H. STRAUSS
This chapter reviews literature on the assessment of emotional processing in brain-

damaged populations. By emotion, we refer to affective behaviors that are relatively
brief in duration. We begin with a brief discussion of the current neuropsychologi-
cal literature pertaining to the assessment of emotion. Next, we turn to the main fo-
cus of the chapter, which is a description of batteries of tests that were developed
specifically to assess emotional processing in neurological populations. Then, be-
cause of the complexity of assessment in this area, we describe procedures com-
monly used for eliciting and evaluating emotional expression. We conclude with rec-
ommendations for future research on the neuropsychological assessment of emotion.
Our focus is on adult brain-damaged and healthy aging populations and not
on psychiatric and developmental issues, which are beyond the scope of this chap-
ter. The chapter provides a compendium of emotional processing tests that can
be used as a foundation for research, assessment, and rehabilitation purposes.
The reader should note, however, that many of these tests are in the develop-
mental stages and may not be commercially available.
BACKGROUND
Within the neuropsychological literature, there is a dearth of information about

assessment of emotion (Cripe, 1996; Tarter & Edwards, 1986). This observation
80
Assessment of Emotional Processing 81
was confirmed by our review of recent textbooks focusing on neuropsychologi-

cal assessment (Filskov & Boll, 1991; Incagnoli, Goldstein, & Golden, 1986;
Lezak, 1995; Spreen & Strauss, 1998). In general, these textbooks present a va-
riety of self-report inventories that examine mood, personality, well-being, and
social adjustment. For the most part, these inventories (e.g., Beck Depression In-
ventory, Minnesota Multiphasic Personality Inventory [MMPI], and Symptom
Check List-90) were developed for use with psychiatric populations (Reitan &
Wolfson, 1997). When clinicians have examined affective behaviors, they have
taken a descriptive approach and conducted bedside evaluations, analogous
to what is used in a neurological/psychiatric mental status examination (e.g.,
Ruckdeschel-Hibbard, Gordon, & Diller, 1986). The social functioning invento-
ries tend to focus on evaluating the extent of physical and social dysfunction
within the context of activities of daily living (e.g., Tarter & Edwards, 1986).
Those authors who do point to the need for assessment procedures for emotional
processing indicate methodological and psychometric issues as problematic in
standardizing potential measures in this area (e.g., Nelson & Cicchetti, 1995).
Furthermore, they often cite the need for theoretical grounding in this area and
the need for the development of tools that assess various discrete aspects of emo-
tional functioning (Cripe, 1996).
REVIEW OF THE EMOTIONAL ASSESSMENT LITERATURE:

TEST BATTERIES AND RELATED STUDIES OF
EMOTIONAL PROCESSING
Our goal has been to simplify and organize the literature on the neuropsycho-
logical assessment of emotional processing. We assumed a componential ap-
proach (Borod, 1993b), which conceptualizes emotion as consisting of a number
of aspects or components that are presumed to be mediated by different neural
substrates (Borod et al., in press; Cripe, 1997; Gainotti, Chapter 9, this volume).
For our purposes, the components and their respective elements include pro-
cessing modes (i.e., perception, arousal, experience, expression, and goal-directed
behavior) (Plutchik, 1984) and communication channels (i.e., facial, prosodic,
lexical, gestural, postural, and scenic). By a scene, we refer to the total arrange-
ment and interactions of stimuli that form the envkonment in which a situation
occurs, for example, a line drawing of a man being held at gunpoint for the emo-
tion of fear (Cicone, Wapner, & Gardner, 1980). Given the complexity of the
brain-behavior relationships for emotion, the componential approach provides a
useful model for organizing this literature. This approach is predicated on a long-
standing issue in the overall emotion literature (Buck, Miller, & Caul, 1974;
Levitt, 1964; Mebrabian & Reed, 1968), including more recent work in the neu-
ropsychology of emotion literature (e.g., Borod et al., 1986; Bowers, Bauer, &
Heilman, 1993; Gainotti, Caltagirone, & Zoccolotti, 1993; Semenzaet al., 1986),
namely, whether there are separate or overlapping systems in the brain underly-
ing emotional processing.
Based on this theoretical perspective, we selected batteries of emotion tests
with more than one element within a component (i.e., processing mode and/or
communication channel). In this review, the primary modes included are per-
ception, expression, and experience, and the channels included are facial,
prosodic, lexical, gestural, postural, and scenic. Batteries reviewed were designed
or specifically adapted for brain-damaged populations. For each battery, we pro-
vide a brief description of each task included; targeted populations; psychomet-
ric properties, where available; and general research findings. In addition, related
studies including measures of emotion, although not necessarily called "batter-
ies" by the authors of the studies, were reviewed and integrated into this section.
Table 4.1 lists the batteries and related studies, specified by mode and channel.
Psychometric information regarding reliability, validity, standardization, and
norms is not systematically included because it was not provided for many of
the published reports reviewed in this chapter. Accordingly, we refer the reader
to individual authors. Due to space limitations, our focus here is descriptive. Fu-
ture reviews of this literature would benefit from a more systematic conceptual
and methodological critique of emotion assessment techniques.
A Single Processing Mode via Multiple Channels
Perception
Profile of Nonverbal Sensitivity. Benowitz and colleagues (1983) used the Profile
of Nonverbal Sensitivity (PONS) (Rosenthal et al., 1979) to assess emotional
perception ability across three channels (facial, prosodic, and body movement).
The body movement channel examines the neck to the knee, focusing on ges-
tural and postural expression. Stimuli involved 220 2-second film segments
extracted from 20 different emotional scenes portrayed by a woman poser in
four emotional categories (positive-dominant, positive-submissive, negative-
dominant, and negative-submissive). Each of the 20 scenes is presented in 11
different formats: face (F) alone, body (B) alone, prosody via content-filtered
speech (PCF), prosody via randomly spliced speech (PRS), F/B, F/PCF, F/PRS,
B/PCF, B/PRS, F/B/PCF, and F/B/PRS. For each item, the subject is required to
select one of two alternative descriptions (e.g., positive-dominant). In the
Benowitz et al. study (see Benowitz, 1980; Benowitz et al., 1983), the full PONS
was administered to seven right brain-damaged (RBD) (M age = 48.9 years) and
four left brain-damaged (LBD) (M = 46.3 years) patients, and an abbreviated
version of the PONS (containing 80 items in which only single-channel items
Table 4.1. Literature Included in the Emotional Assessment Review as a Function of Processing Mode and Communication Channel
PROCESSING MODE COMMUNICATION CHANNEL
BODY
BATTERY PERCEP- EXPRES- EXPERI- BE- LEXI- GES- MOVE- MISCELLA-
CATEGORY STUDY (IF AVAILABLE) TION SIGN ENCE AROUSAL HAVIOR FACIAL PROSODIC CAL TURAL MENT SCENES NEOUS
Single
mode/ Benowitz et Profile of X X X X
multiple al. (1983) Nonverbal
channels Sensitivity
(PONS)
Egan et Perception X X X X
al. (1990) of Emotion
Test
(POET)
Mountain Victoria X X X
(1993) Emotion
Perception
Test
(VERT)
Bowers et Florida X X X
al. (1991); Affect
Blonder et al. Battery
(1991) (FAB);
selected X X
study
(Continued)
Table 4.1. Literature Included in the Emotional Assessment Review as a Function of Processing Mode and Communication Channel (Continued)
PROCESSING MODE COMMUNICATION CHANNEL
BODY
BATTERY PERCEP- EXPRES- EXPERI- BE- LEXI- GES- MOVE- MISCELLA-
CATEGORY STUDY (IF AVAILABLE) TION SIGN ENCE AROUSAL HAVIOR FACIAL PROSODIC CAL TURAL MENT SCENES NEOUS
Lalande et Selected X X x
al. (1992) study
Cicone et Selected X X x x
al. (1980) study
Heath et Selected X X x X x*
al. (1997) study
Single
channel/ Ross et Aprosodia X x X
multiple al. (1997) Battery (AB)
modes Meadows Selected X x X
& Kaplan study
(1994)
Multiple
modes/ Cancelliere Battery of X X
multiple & Kertesz Emotional
channels (1990) Expression & X X x X
Comprehension
(BEEC)
Borod et X X x
N e w YorkzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA
X X X
al. (1992) Emotion
Battery
(NYEB)
Hornak et Selected X X X
al. (1996) study X X
Weddell Selected X X X X
(1994) study X X
X
Cohen et Selected X X X
Blonder et Selected X X X X
Scott et Selected X X X
Borod et Experimental X X X X
al. (1990) affect
battery
*Affective state.
were presented) was given to one right-hemispherectomized patient (age = 24

years) and four commissurotomized patients (M = 40.3 years). As might be ex-
pected, the data revealed right-hemisphere superiority for the ability to evaluate
emotional information.
Perception of Emotions Test. The Perception of Emotions Test (POET) (Egan et

al., 1990) is a test of emotional perception across three channels (facial, prosodic,
and verbal), separately and combined. Stimuli involve 128 6-second video/audio
segments with emotional components portrayed by two men and two women. Four
emotions are portrayed (anger, happiness, sadness, and neutrality) in each of four
conditions: facial expressions without sound; prosodically intoned scripts with
neutral content (no video); verbal emotional scripts presented in a neutral tone of
voice (no video); and combined scenes with emotional content in all three chan-
nels simultaneously. After stimulus presentation, the subject has 8 seconds to re-
spond by pointing to one of four drawings, each with a verbal label depicting each
of the emotions. The real-time presentation of emotional stimuli across channels
provides a degree of ecological validity. The POET was originally administered
to 100 normal adults (M = 22.2 years), 11 LBD patients (M = 65.9 years), and
10 RED patients (M = 63.6 years) (Egan et al., 1990). In addition, the facial stim-
uli were adapted for use with positron emission tomography (Egan et al., 1996),
showing more frequent right-hemisphere activation.
Victoria Emotion Perception Test The Victoria Emotion Perception Test (VERT)
(Mountain, 1993) evaluates emotional perception across two channels (facial and
prosodic), both separately and combined. The VERT is comprised of three sub-
tests (facial, prosodic, and combined), each consisting of 24 paired-items in-
volving photographs of facial emotional expressions and prosodic emotionally
intoned strings of nonsense words. There are four emotions (anger, sadness, hap-
piness, and fear) presented at three intensity levels (mild, moderate, and extreme).
For each item-pair, the subject is required to make four separate forced-choice
judgements: a same-different discrimination with respect to emotional category
and intensity level, and an identification of the discrete emotion and the inten-
sity level.
The battery (VERT Research) was designed for use with clinical populations
suffering from emotional disorders and was originally normed and standardized
on young and elderly normal adults. The VERT Clinical consists of half of the
items selected for item stability. The VERT provides age-related norms (based
on two samples of young adults [N1 = 13, M = 27.2 years; N2 = 18, M = 24.5
years] and one sample of older adults [N = 9,M = 72 years]) and reliability data
(internal consistency and test-retest). For construct validity, a significant posi-
tive correlation was found between the PONS and both versions of the VERT
(Mountain & Spreen, 1993).
Florida Affect Battery and related study. The Florida Affect Battery (FAB) (Bow-
ers, Blonder, & Heilman, 1991) is a comprehensive battery, consisting of ten
subtests, for the assessment of emotional perception across facial and prosodic
channels. For both channels, five emotions are studied (i.e., happiness, sadness,
anger, fear, and neutrality), and there are an emotional identification and dis-
crimination task, as well as a nonemotional discrimination task. For face, there
are two additional emotional subtests, one involving comprehension and one in-
volving matching. Finally, there are two reciprocal cross-modal subtests involv-
ing facial and prosodic emotional stimuli. All subtests for these two channels
have 20 items (5 emotions X 4 items) except for the prosodic nonemotional sub-
test, which has 16 items.
Blonder, Bowers, and Heilman (1991) included two lexical tasks in a study
incorporating the FAB. The tasks were comprised of 56 verbal sentence de-
scriptors of nonverbal expressions (face, voice, and gesture; e.g., "tears fell from
her eyes" and "she laughed") and comprehension of 75 emotional sentences (e.g.,
"you were delighted by the bonus"). The latter task contains no words describ-
ing facial, prosodic, or gestural signals and contains three levels of inferential
complexity (denotations, words and phrases associated with particular emotions,
and contextual cues requiring inferences).
The FAB and the two lexical tasks were administered (Blonder, Bower, &
Heilman 1991) to ten RBD (M = 64.1 years), ten LBD (M = 59.6 years), and
ten normal control (NC) (M = 63.2 years) right-handed adults. Right brain-
damaged subjects showed deficits in discriminating and matching facial emotion,
identifying and discriminating emotional prosody, and identifying sentences
depicting nonverbal expressions. The FAB has also been administered to
Alzheimer's disease patients (Cadieux & Greve, 1996), who showed some
deficits, and to a global aphasic patient with a large left hemisphere lesion (Bar-
rett et al., 1999), who showed preserved performance on nonverbal affect recog-
nition tasks.
Related studies. Lalande et al. (1992) examined verbal and prosodic emotional
perception in unilateral right (N = 12, M = 61.8 years) and nonaphasic left (N =
10, M = 58 years) stroke patients and in 16 NCs (M = 61 years). Six emotions
were studied (joy, anger, fear, disgust, surprise, and sadness), and 36 taped
phrases were used for all tasks. For the verbal contextual task, neutrally intoned
phrases were presented auditorily. For the pure prosody task, hummed phrases
with emotional intonation were presented auditorily (e.g., "propulsive growling,"
"whining," and "screaming"). For single-channel tasks, an identification para-
digm was used. For the cross-modal task, a discrimination paradigm was used;
18 phrases were presented in a content-concordant tone, and 18 were discordant.
Hemisphere-specific deficits were reported, with RBDs impaired on the pure
prosody and cross-modal tasks and LBDs on the verbal contextual task.
Cicone, Wapner, and Gardner (1980) studied the perception of positive emo-
tions (happiness, surprise-glee, excitement, and/or love) and negative emotions
(i.e., sadness, disgust, fear, and anger) in facial expressions, verbal/phrasal de-
scriptors, and pictorial scenes. Six emotions were used per task, and a multiple-
choice recognition paradigm was employed with both verbal and pictorial for-
mats. Subjects were 18 LBD patients (M = 49 years) and 21 RED patients (M =
58 years) of various etiologies. Demographically matched and age-matched con-
trol subjects were ten hospital patients being treated for non-neurological illness.
A second group of control subjects included 13 bifrontal leukotomy patients (M =
55 years). Although LBDs showed a selective deficit for linguistic stimuli, RBDs
demonstrated a reduction in emotional sensitivity across channels.
Expression
Related study. In a recent innovative study by Heath et al. (1997) utilizing a

naturalistic observational approach, spontaneous expression during a neuropsy-
chological evaluation was observed and rated for the occurrence of facial ex-
pression, intonation, eye contact, and affective state. Two ethnographers deter-
mined the frequencies of occurrences for each channel, and most subjects were
observed more than once. Subjects were unilateral stroke patients with RED (N =
4, M = 65.5 years) and LBD (N = 7, M = 60.7 years) and normal hospital con-
trols (N = 7,M = 69.4 years). Although both stroke groups showed difficulty in
facial expressiveness and in conveying affective state, the patients with right-
hemisphere pathology also showed selective impairments in intonation and in es-
tablishing eye contact.
A Single Channel via Multiple Processing Modes
Prosody
Aprosodia Battery. The Aprosodia Battery (AB), recently described by Ross,

Thompson, and Yenkosky (1997), originated in earlier work by Ross in the 1970s
and 1980s (see Ross, 1985; Ross & Mesulam, 1979). This battery arose from
clinical neurological observations of altered prosodic components of speech in
RBDs and was originally developed for bedside evaluation. Furthermore, the ba-
sis of the battery and Ross's conceptualization of the aprosodias vis-a-vis the
right hemisphere are grounded in neuroanatomical models of language organi-
zation for the left hemisphere (e.g., Goodglass & Kaplan, 1983).
The AB examines prosody across expressive (posed repetition and sponta-
neous) and comprehension (identification and discrimination) processing modes.
Six emotional categories (neutral, happiness, surprise, sadness, anger, and disin-
terested) are examined for all aspects of the battery except for spontaneous ex-
pression for which one positive and three negative scenarios are used to elicit re-
sponses. The posed repetition tasks include 12 stimuli in each of three conditions
(words, monosyllables [e.g., "ba"], and asyllables [e.g., "aaahhhhhhhh"]). The
comprehension tasks include 24 stimuli for identification across three conditions
(words, monosyllables, and asyllables) and for discrimination across one condi-
tion (filtered words). For the identification tasks, subjects are required to select
one of six choices presented as line drawings of faces with verbal labels. For the
expression tasks, Ross has developed extensive procedures for computer-assisted
acoustical analysis (e.g., Ross, 1997; Ross, Edmondson, & Seibert, 1986; Ross
et al., 1987). Trained judges also rate the posed voice recordings for affective
category and for intensity. Ross's battery has been used to determine the
relationship between aprosodic syndromes (e.g., sensory aprosodia and motor
aprosodia) and neuroanatomical sites via template mapping of brain lesions for
functional-anatomical correlations (Gorelick & Ross, 1987; Ross, 1981). Find-
ings from the work of Ross and colleagues have suggested that anterior portions
of the right hemisphere are important for the production of emotional prosody,
whereas posterior regions of the right hemisphere are important for the compre-
hension of emotional prosody.
Emotional situations/scenes
Related study. In a study by Meadows and Kaplan (1994), autonomic and sub-
jective responses to emotional and neutral slides (Buck, 1978) were evaluated in
12 RBD subjects (M = 63.2 years) and nine LBD subjects (M = 64.6 years) with
cerebrovascular accidents and in 25 NC subjects (M = 55.8 years). The com-
munication channel utilized in this study (i.e., "scenes") employed emotionally
charged scenarios or scenes. The psychophysiological measures were skin con-
ductance and heart rate, and subjects were required to identify the content of each
slide and rate their subjective experience on a 9-point Likert pleasantness scale.
Although the groups did not differ in subjective ratings, the RBDs showed a sig-
nificant reduction in autonomic arousal as measured by skin conductance.
Multiple Processing Modes Via Multiple Channels
Battery of Emotional Expression and Comprehension

The Battery of Emotional Expression and Comprehension (BEEC) (Cancel-
liere & Kertesz, 1990) assesses posed emotional expression for the prosodic chan-
nel and emotional perception for faces, prosody, and scenes. For expression, there
are two prosodic subtests, one involving posing to verbal command and the other
posing to imitation ("repetition"). Each subtest contains 16 neutral-content sen-
tences, and four expressions are elicited (happiness, sadness, anger, and neutral-
ity). Procedures are described for the evaluation of prosodic expressions, via
trained raters, for both valence and pitch (on a 7-point Likert scale). For per-
ception, each identification subtest contains the four expressions mentioned
above. There are 20 items for facial and prosodic emotion and 16 items for line
drawings of emotional scenes (e.g., a child opening a Christmas gift). The BEEC
was administered to unilateral stroke patients (who were relatively acute) (28
RBDs and 18 LBDs [M = 62.5 years]) and to 20 NCs (M = 62.4 years) and was
studied with respect to computed tomography scan lesion localization and
aprosodic syndromes (Cancelliere & Kertesz, 1990). Results did not reveal dif-
ferences as a function of lesion side, but lesion site differences were observed,
with deficits most prominent for basal ganglia, anterior temporal, insula, and peri-
sylvian regions.
New York Emotion Battery

The New York Emotion Battery (NYEB) (Borod, Welkowitz, & Obler, 1992)
originates in a componential approach to emotional processing (Borod, 1993b)
and examines emotional expression (posed and spontaneous), perception (iden-
tification and discrimination), and experience across facial, prosodic, and lexical
channels. There are three positive emotions (happiness, interest, and pleasant sur-
prise) and five negative emotions (anger, disgust, fear, sadness, and unpleasant
surprise). In addition, the battery includes screening measures and nonemotional
control tasks for each channel and processing mode. The categories for the non-
emotional tasks are characteristics of people (e.g., vision) for perception, every-
day activities (e.g., bought something for the house) for spontaneous expression,
and relatively abstract imageable words ( e.g., space) for posed expression. Sub-
tests of the battery have analogous psychometric properties (e.g., structure and
administration procedures) across the three channels. In addition, in developing
the perception tasks (Borod et al., 1998), normal adults rated each stimulus item
as belonging to a particular emotional category (e.g., happiness) at 80%, on the
average, across channels, paradigms, valences, and discrete emotions.
Identification tasks for prosodic and lexical channels consist of 24 items each,
and 32 items are included for the facial channel; discrimination tasks include 28
stimulus pairs. For facial stimuli, slides developed by Borod, Welkowitz, and Obler
(1992) and by Ekman and Friesen (1976) are used. There are two lexical identi-
fication tasks, one with single words and one with complete sentences. For posed
expression, the eight emotional expressions are produced to verbal command and
imitation. For spontaneous expression, subjects recollect recent experiences
("monologues") for each emotion. For analysis of expression data, raters evaluate
facial expressions via video without sound, prosodic expressions via audio, and
lexical expressions via transcripts. Trained raters analyze expressions for category
accuracy and emotional intensity using procedures developed by Canino et al.
(1999) for posed expressions in all three channels, by Montreys and Borod (1998)
for spontaneous facial expressions, and by Borod et al. (1996) for spontaneous lex-
ical expression. (See also Tabert et al. [1997] for a word error-type analysis of the
posed lexical expression data). Emotional experience is evaluated via Likert-scale
self-report measures of intensity and accuracy after each monologue.
The perception measures of the NYEB were administered to 11 RED stroke
patients (M = 67.1 years), 10 LBD stroke patients (M = 63.2 years), and 15 NC
adults (M = 64.8 years) (Borod et al., 1998). On identification measures, RBDs
were significantly impaired relative to LBDs and NCs across all three channels;
for discrimination measures, no group differences emerged. In a follow-up study
focusing on language deficits, Cicero et al. (1999) found that the performance of
LBDs with language deficits was facilitated, whereas the performance of RBDs
was suppressed on the emotional sentence identification task. In addition, parts
of or adaptations of aspects of the NYEB have been used in Borod's laboratory
to study emotional communication in temporal lobe epileptics (Santschi-Hay-
wood et al., 1996,1997), hemiparkinson's disease patients (St. Clair et al., 1998),
and healthy normal adults across the lifespan (Grunwald et al., 1999), and to ex-
amine the recovery of emotional functioning after stroke.
Related studies
Hornak, Rolls, and Wade (1996} examined emotional facial and prosodic per-
ception, subjective experience, and behavior in brain-injured patients with postin-
jury histories of socially inappropriate behavior. Patients had either head injury
or stroke; there were 12 patients with ventral frontal lobe damage (M = 41.4
years) and 11 with nonventral (e.g., parietal or basal ganglia) damage (M = 47.4
years). For facial perception, the emotions used were happiness, surprise, anger,
disgust, fright, sadness, and neutrality; for prosodic perception, the emotions used
were contentment, puzzlement, anger, disgust, fright, sadness, and neutrality. The
prosodic paradigm involved nonverbal expressions (e.g., "ugh" and "yuck" for
disgust) rather than emotionally modulated speech to make it easier for brain-
injured patients to process. To evaluate experience, a subjective emotional change
questionnaire was used. To evaluate "behavior," a questionnaire was used in-
volving a range of behavioral problems (e.g., disinhibition) occurring in social
milieus. A member of the patient's rehabilitation team completed the question-
naire. There was a positive correlation between the degree of altered emotional
experience and the severity of behavioral problems. The use of both subjective
and objective measures of emotion enables a more refined examination of pro-
cessing mode relationships and has implications for clinical rehabilitation. The
focus of this work (Hornak, Rolls, & Wade, 1996) was on caudality rather than
laterality. Results demonstrated that the ventral patients were more impaired than
the nonventral patients on the perceptual and experiential measures.
Weddell (1994) examined the effects of subcortical lesion site on emotional
expression and perception. Subjects were 10 patients with damage to structures
of the third ventricle (M = 43.5 years), 61 patients with focal cerebral lesions
(M = 50.7 years; 27 RBDs and 24 LBDs), and 15 non-brain-damaged patients
with spinal cord lesions. For expression, both spontaneous and posed facial ex-
pressions were elicited and evaluated via the Facial Action Coding System (Ek-
man & Friesen, 1978). Spontaneous expression included both positive and neg-
ative responses (Weddell, Trevarthen, & Miller, 1988); posed expressions
included happiness, anger, disgust, and surprise (Weddell, Miller, & Trevarthen,
1990). For perception, facial, prosodic, and lexical channels were evaluated via
emotional and neutral-content sentences and utterances; emotions included hap-
piness, sadness, anger, surprise, and neutrality. In addition, a recognition mem-
ory paradigm (Weddell, 1989) was used for the facial channel. Finally, behavior
was assessed with a semistructured interview that focused on social-emotional
behaviors, appetitive disturbances, and psychiatric symptoms. In general, patients
with hypothalamic damage exhibited appetitive disorders; patients with cerebral
lesions, especially right medial temporal involvement, demonstrated impaired
emotional recognition; and patients with frontal and basal ganglia damage dis-
played impoverished facial emotional expression.
Cohen, Riccio, and Flannery (1994) reported a case study of a 16-year-old girl
with a unilateral right-hemisphere basal ganglia embolic stroke that used multi-
ple channels and modes. For perception, the patient was administered a test in-
volving the identification of emotional gesturing via videotape, emotional
prosody in audiotaped sentences, and a combination of gesturing and prosody.
The emotions used were happiness, sadness, and anger. For expression, the pa-
tient was required to intone sentences and to imitate prosodically intoned sen-
tences; expressions were evaluated for appropriateness by two independent raters.
The measures were administered immediately after the stroke and again 4 months
later. During both assessments, the patient was able to comprehend emotional
gestures and prosody but showed a deficit in expressing emotional prosody. Pro-
cedures for the evaluation of gestural communication have been previously de-
scribed by Ross (1985, 1997) for clinical examination and by Blonder et al. (1995)
in an experimental paradigm.
In another study examining unilateral hemispheric pathology (in hemi-
parkinson's disease [HPD]), Blonder, Gur, and Gur (1989) evaluated the ex-
pression of emotional prosody and the perception of emotion across three chan-
nels. There were 14 right HPDs (M = 61 years), 7 left HPDs (M = 62 years),
and 17 NCs (M = 62.4 years). For the expressive task, subjects were required
to make and imitate semantically neutral sentences in five different emotional
tones (happiness, puzzlement, anger, sadness, and neutrality). These expressions
were subsequently rated for intensity and/or accuracy. For perception, subjects
were required to identify emotions conveyed by facial expressions (Ekman &
Friesen, 1975), intoned neutral sentences, and semantically emotional sentences.
Nonemotional control tasks for the prosodic (e.g., receptive linguistic prosody
[Weintraub, Mesulam, & Kramer, 1981]) and facial ( e.g., identification of fa-
mous faces) channels were included to control for cognitive and perceptual
deficits (e.g., visuospatial deficits for the facial channel) commonly seen in
Parkinson's disease. Although there were expressive and receptive emotional
deficits for HPDs relative to NCs, there were no differences as a function of lat-
erality, suggesting bilateral involvement in emotional processing at the subcor-
tical level. To our knowledge, this was the first study to examine emotional pro-
cessing in HPD.
An evaluation of Parkinson's disease conducted by Scott, Caird, and Williams
(1984} involved 28 patients with Parkinson's disease (M = 63 years) and 28 el-
derly NCs (M = 70 years). Perception was evaluated in two channels, and ex-
pression was evaluated in one. For expression, prosodic production of a single
emotion (i.e., anger) via a brief sentence was examined and scored for accuracy.
For perception, matching tasks containing several facial and prosodic emotional
stimuli were administered. Overall, the Parkinson's disease patients were im-
paired relative to NCs in expressing and perceiving emotion.
Finally, we conclude with a study by Borod et al. (1990) that examined emo-
tional expression and perception in 20 Parkinson's disease patients (M = 65.7
years), 19 unilateral right-sided stroke patients (M = 63.5 years), psychiatric pa-
tients (i.e., 20 schizophrenic [M = 39.1 years] and 12 unipolar depressive [M =
56.4 years]), and 21 NCs [M = 56.9 years]). An experimental affect battery was
used to examine the perception and expression of facial and prosodic emotion.
As emotional valence was a focus of this study, three positive emotions (happi-
ness, pleasant surprise, and interest) and four negative emotions (anger, sadness,
fear, and disgust) were assessed across all tasks. For expression, subjects were
required to pose, facially and prosodically, these emotions to oral command.
Video and audio recordings of the expressions were later evaluated by naive
judges for emotional intensity, category accuracy, and valence accuracy. For per-
ception, both identification and discrimination paradigms were used, involving
photographs of facial emotion (Ekman & Friesen, 1976) and intoned neutral-con-
tent sentences (e.g., "fish can jump out of the water"; Tucker, Watson, & Heil-
man, 1977). Reliability data were provided for the tasks—interrater agreement
for expression and internal consistency for perception. Schizophrenics showed
the most impairment in expressing and perceiving emotions, followed by RBDs
and Parkinson's disease patients, then by unipolar depressive patients, with NCs
showing the least impairment. Borod et al. (1990) examined relationships be-
tween facial and prosodic channels and between expressive and perceptual pro-
cessing modes. Although there were positive associations between facial and
prosodic channels, measures of perception and expression were less strongly
correlated.
EMOTIONAL EXPRESSION
This section provides information about examining emotional expression in neu-

rological populations. Note that the procedures described come from basic emo-
tion research with normal people and from the psychiatric literature. Both ex-
pression elicitation and evaluation procedures are provided. With respect to
evaluation, essentially there are two approaches, one focuses on external ex-
pression and the other on internal states and dispositions.
Elicitation Procedures
Typically, for external expression, emotion is induced via elicitation procedures

involving the presentation of emotionally evocative stimuli. In work with brain-
damaged individuals, both auditory (e.g., mood-induction) and visual (e.g., slide-
presentation) stimuli are employed. For example, mood-induction procedures
reported in the literature primarily involve verbal statements (e.g., Velten, 1968)
and sometimes nonverbal stimuli (e.g., facial expressions [Dimberg, 1982;
Schneider et al., 1995] and video clips from movies [Davidson, 1995; Tomarken,
Davidson, & Henriques, 1990]). In terms of slide-presentation procedures, for
example, one set of stimuli frequently used in neuropsychological research is the
set developed by Buck (1978). It consists of 32 photographs (in slide format)
representing five separate categories: scenic (e.g., sunset over a lake), pleasant
(e.g., young child touching flowers), sexual (e.g., embracing couple), unusual
(e.g., multiple exposures of an airport), and unpleasant (e.g., starving child). An-
other set of slides used extensively in emotion research with normal individuals
that can be adapted for use with clinical populations is the International Affec-
tive Picture System (IAPS) (Lang, Ohman, & Vaitl, 1988). As described by Lang
et al. (1993), the IAPS consists of 240 slides that have been conceptualized across
several dimensions, that is, valence (pleasantness/unpleasantness), arousal
(calm/arousing), and dominance (or control). Employing another approach that
focuses on expression rather than perception to induce a mood, Schiff and La-
mon (1989) have used unilateral facial manipulation to induce pleasant and un-
pleasant mood states.
Evaluation Procedures
Observations of external expression

Once expressions are elicited and recorded, they are typically subjected to
ratings by trained judges or to analytical techniques for a specific channel.
In the case of ratings, the most commonly used measures with brain-
damaged individuals are accuracy (or appropriateness), expressivity (or frequency),
and intensity (for review, see Borod, 1993a). Subjects' expressions are recorded
(via audio, video, and/or transcription procedures) and then evaluated by judges
who are naive to the characteristics of the patients. It is essential to train the judges
and to establish a high degree of interrater reliability. The following references pro-
vide examples of rating procedures frequently used, by channel: facial channel—
Blonder et al., 1993; Borod et al., 1988; Kolb & Taylor, 1990; Malatesta & Izard,
1984; Oster, Hegley, & Nagel, 1992; Weddell, Miller, & Trevarthen, 1990; prosodic
channel—Banse & Scherer, 1996; Borod et al., 1990; Ross, 1997; Sobin & Alpert,
1999; lexical channel—Bloom et al., 1990, 1992; Borod et al., 1996; Cimino et al.,
1991; and gestural channel—Blonder et al., 1995; Ross, 1997. Some investigators
have developed rating procedures that are standardized across multiple channels
(Borod et al., 1990; Canino et al., 1999).
There are also a number of techniques for quantification of features related to
each of the communication channels: muscle action units for the facial channel
(Facial Action Coding System [Ekman & Friesen, 1978] and the Maximally Dis-
criminative Facial Movement Coding System [Izard, 1983]); acoustical parame-
ters (e.g., frequency, duration, pitch, and amplitude) for the prosodic channel
(Alpert et al., 1989; Martz & Welkowitz, 1977; Ross et al., 1987; Shapiro &
Danly, 1985; Welkowitz, Bond, & Zelano, 1990); and discourse and word analy-
sis (e.g., length, frequency, structure, and grammatical type) for the lexical chan-
nel (Bloom et al., 1994; Davitz, 1964; Tabert et al., 1997). For a review of com-
puterized voice analysis software (i.e., Computerized Speech Laboratory,
CSpeech, and Sound Scope), see Bielamowicz et al. (1996).
Observations of internal states and dispositions

To obtain a patient's evaluation of his or her own experience while producing
emotional expressions, typically, individuals are asked to produce self-reports
about internal subjective experience. Although clinicians often rely on such stan-
dard measures as the MMPI-2 (Gasparrani et al., 1978; Greene, 1992), Person-
ality Assessment Inventory (Morley, 1991), Rorschach (Rorschach, 1942), and
Thematic Aperception Test (Murray, 1938), our focus here is on novel and of-
ten experimental measures developed specifically for neurological populations.
Within a neuropsychological context, use of more routine tests, such as the
MMPI-2 and Rorschach, may be contraindicated because of their heavy demands
on attention, concentration, comprehension, and/or perceptual skills. Neurologi-
cal insult often results in deficits in these domains, rendering administration and
interpretation of test results problematic. In a related vein, some concerns en-
dorsed by patients (e.g., fatigue and hallucinations) may be caused by valid neu-
rological dysfunction and therefore should not be considered a reflection of the
patient's emotional state. For a more detailed description of standardized as-
sessment techniques, see Exner (1986), Graham (1993), and Spreen and Strauss
(1998).
To assess internal experience, Likert-type scales are generally employed

(ranging from minimal to maximal), and the amount of emotional intensity or
accuracy is assessed (e.g., via the Differential Emotions Scale [Izard, 1972]).
These scales typically apply to one's experience at the moment with respect to
the "affect" elicited by a particular stimulus. To evaluate "mood," which is
longer lasting and more stable in duration than affect, a number of scales have
been developed for use with brain-damaged populations (for review, see Sweet
et al., 1992). For depression, examples of scales are the Geriatric Depression
Screening Scale (Yesavage et al., 1983), the Post-Stroke Depression Rating Scale
(Gainotti et al., 1997), and the Structured Assessment of Depression in Brain-
Damaged Individuals (Gordon et al., 1991). Taking a broader approach, Nelson
et al. (1989) developed the Neuropsychology Behavior and Affect Profile to use
with neurological populations and to assess five areas: inappropriateness, indif-
ference, depression, pragnosia ("defects in the pragmatics of conversational
style"), and mania. In a similar vein, Levin et al. (1987) developed the Neu-
robehavioral Rating Scale, adapted from the Brief Psychiatric Rating Scale
(Overall & Gorham, 1962), to document behavioral sequelae of brain damage
(e.g., anxiety, depressive mood, lability, and suspiciousness). The scale is de-
signed for patients who are unable to fill in self-report inventories; it is com-
pleted by a clinician or interviewer familiar with the patient. Finally, the Port-
land Adaptability Inventory (O'Brien & Lezak, 1988) was developed to evaluate
a patient's emotionality (e.g., irritability, depression, and delusions) and social
adaptation (e.g., appropriateness and employment) via a trained observer and a
rating scale.
To obtain a sense of a person's inner experience, personality inventories have
been used. They typically capture traits and characteristics of personality over
an extended period of time. One such questionnaire is the Temporal Lobe
Epilepsy Questionnaire developed by Bear and Fedio (1977) to assess charac-
teristics of temporal lobe epilepsy (e.g., circumstantiality, religiosity, emotional-
ity, humorlessness, and euphoria). Another inventory, the Friedes Neuropsycho-
logical Personality Survey (Friedes, 1991), attempts to integrate aspects of
personality (e.g., endurance, aggression, disorganization, and anxiety) with cor-
tical levels of arousal.
CONCLUSION
In summary, several tests have been developed recently to assess emotional pro-
cessing in brain-damaged individuals. In their current state, these measures are
best regarded as research tools. Although these tests and batteries hold consid-
erable promise, much more work needs to be done if they are to be used in the
clinical setting.
Currently, these batteries and procedures have both conceptual and method-
ological limitations. From a conceptual perspective, there is the issue of construct
validity. Many tasks/inventories have been developed, yet few provide both con-
vergent and divergent evidence for construct validity. Furthermore, most studies
have been performed by the authors of the particular tests. Data from diverse lab-
oratories are important to provide validating evidence. In addition, large-scale
studies of normal persons and a range of patient populations are needed to allow
meaningful evaluation of the performance of an individual patient. Another type
of validity that needs to be addressed is ecological validity because "the scores
derived from such tests may have little bearing on the patient's ability to function
in his or her environment or society" (Sbordone, 1996, p. 16). With regard to fu-
ture work in this area, investigators might want to borrow from the literature on
functional communication (e.g., Borod et al., 1989; Holland, 1980; Sarno, 1969)
and social skills training (e.g., Brozgold et al., 1998; Mueser et al., 1996); they
have dealt with ecological validity in perhaps a more direct fashion and have de-
veloped measures that can be used in more naturalistic settings. In general, test
validity depends on three elements: content, criterion-related, and construct va-
lidity. Although these principles have typically been central to the development
of tests within the cognitive domain, attention to such procedures should also help
to clarify and refine the meaning of various aspects of emotional processing.
From a methodological perspective, the measures reviewed here need consid-
erable work with respect to psychometric features (e.g., standardization, norms,
and reliability). Several emotion tests do provide substantive information about
the psychometric properties of the procedures used. These tests focus on a sin-
gle channel and on a single processing mode and thus were not reviewed above.
One is a test of facial emotion identification, using standard slides (Ekman &
Friesen, 1976), developed by LeFever (1988) for use with normal adults. A sec-
ond is a facial emotion discrimination task developed by the Gurs and colleagues
for use with normal (Erwin et al., 1992), depressed (Gur et al., 1992), and schiz-
ophrenic (Heimberg et al., 1992) individuals. The third is a prosodic emotion
identification task (Emotional Perception Test) that has been normed for children
(Allen, personal communication, 1998) and for adults across the lifespan (Green,
1996). To move beyond a single channel and mode, in our own work on the
NYEB, we are currently establishing reliability for both perception measures
(Borod et al., in press) and expression measures (Canino et al., 1999) across mul-
tiple channels, and we are developing norms across the lifespan.
An interesting area for future research entails the use of emotional stimuli in
neuropsychological evaluations of cognitive functions (e.g., attention via the
Emotional Stroop Task [Williams, Matthews, & McLeod, 1996] and memory via
the Affective Auditory Verbal Learning Test [Snyder & Harrison, 1997]). In ad-
dition, such procedures may allow researchers to unravel the interplay and in-
terdependence between cognitive and emotional processes. Bartolic et al. (1999)
recently demonstrated that cognitive processing (i.e., fluency) associated with the
frontal lobes can vary as a function of dysphoric mood induction (figural flu-
ency, right hemisphere) versus euphoric mood induction (verbal fluency, left
hemisphere). For discussions that explore the relationship between cognition and
emotion, see Oschner and Schacter (Chapter 7, this volume) and Adolphs and
Damasio (Chapter 8, this volume).
ACKNOWLEDGMENTS
This project was supported, in part, by NIMH grant MH42172 to Queens College, by PSC-CUNY
Research Award 668268 to Queens College, and by the Natural Sciences and Research Council of
Canada. We are grateful to Jack Nitschke for his helpful comments on this manuscript.
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5
Neuroimaging Approaches to the
Study of Emotion
MARK S. GEORGE, TERRENCE A. KETTER,

TIM A. KIMBRELL, ANDREW M. SPEER,
JEFF LORBERBAUM, CHRISTOPHER C. LIBERATOS,
ZIAD NAHAS, AND ROBERT M. POST
BACKGROUND
The recent technological revolution in functional neuroimaging has provided new

insights into regional brain activity during normal and pathological emotions and
has advanced understanding of several neuropsychiatric diseases. The list of dif-
ferent functional imaging tools can, however, be daunting for those not actively
working in the area. Additionally, an incomplete knowledge of the nature of the
source of the imaging signal can hinder complete understanding of the results of
imaging studies. Therefore, in this chapter we outline several of the basic prin-
ciples behind the use of functional imaging to study emotion. We then briefly
describe the most commonly used functional imaging techniques and discuss
some of the problems in most of the imaging research in this area. These intro-
ductory comments are illustrated with examples from the imaging literature as
well as from the authors' primary work.
Common Paradigms in Functional Imaging Used To

Examine the Neural Basis of Emotion
Recent advances in imaging techniques now enable direct examination of the

working brain during episodes of clinical depression and during transient emo-
106
Neunoimaging Approaches to the Study of Emotion 107
tions in healthy controls, allowing for more direct testing of hypotheses con-
cerning normal and abnormal neural mechanisms. Studies with these techniques
have confirmed and refined some of the earlier models of how the brain regu-
lates mood and emotion. Functional neuroimaging, however, a field with im-
mense promise, is still in its infancy. Regardless of the imaging method used,
most modern functional imaging studies applied to understanding emotion have
one of the following basic approaches.
1. Single-case study. The classic single-case method involves finding a pa-
tient with a brain lesion who has some disorder related to emotion (e.g., patho-
logical crying). With functional and structural imaging, one then attempts to un-
derstand how the brain regions that were damaged produce this disorderly change
in behavior.
2. Between-group analysis. With between-group analysis, one images a group
of subjects who have a mood disorder and compares them with one or two groups
who vary on an important emotional feature or who were chosen to represent
different ends of a continuous feature. For these analyses to work, attention must
be paid to the activity at the time of the scan and whether there were differences
between groups in the performance of this behavior (commonly used is an au-
ditory continuous performance task). Also, because the sizes and shapes of dif-
ferent brains vary widely, attempts must be made to account for the differences
in brain size for group comparisons. One approach is to measure activity in brain
regions on each individual scan, typically guided by a template or magnetic res-
onance image (MRI) of the subject, and then compare (called a region of inter-
est analysis). Alternatively, one can transform and reshape (called stereotacti-
cally normalizing) the images into a common brain space. The most common
brain atlas used in functional neuroimaging is the Talairach atlas (Talairach &
Tournoux, 1988). The most popular method of normalizing brain scans into
Talairach Space is the statistical software package Statistical Parametric Map-
ping developed by Karl Friston and colleagues at the Hammersmith Hospital
(currently at the National Hospital for Neurological Diseases at Queen's Square)
(Friston et al., 1989, 1990).
3. Within-group analysis. In the within-group method, one commonly per-
forms functional imaging on a group with a disorder of mood or emotion before
and after a change in state (e.g., depressed patients before and after medication
treatment). With nondiseased populations, subjects are imaged at rest and then
during an emotional task, commonly either a mood state induced neuropsycho-
logically or pharmacologically, or while performing a task related to processing
emotion. Again, with this method one must transform the functional brain maps
into a common space and then attempt to examine changes before and after and
then reason back to the role of key brain region changes as a function of the be-
havior, treatment, or state change. Designing carefully constructed activation par-
adigms in which the control condition accounts for everything but the behavior
in question is challenging but vitally important (George, Ketter, & Post, 1994;
Haxby et al., 1991; Ring et al., 1991) (see discussion below as well).
4. Within-individual analysis. The faster, nonradiation-based techniques like
echoplanar blood oxygenation level-dependent (BOLD) functional MRI now al-
low for rapid acquisition of many brain images within an individual. For exam-
ple, in the most common protocol in our laboratory, we acquire an entire brain
volume every 3 seconds continuously over 6 minutes, generating 120 separate
volumes of brain function. By subtly changing activity across these 6 minutes,
one can test, within an individual, for regional brain changes associated with a
specific behavior or emotion. This within-individual ability then eliminates the
need for pooling of data across different individuals in a common brain space.
Certainly functional imaging is not limited to these paradigms or statistical
analysis methods. The near future will likely see many more complex and dy-
namic uses of functional imaging to explore the regional brain basis of mood dis-
orders and emotion. For example, several research groups have developed MRI
sequences that can image regional brain perfusion without requiring paramag-
netic contrast agents (serial perfusion MRI scanning) (Bohning et al., 1996,
1997b; Schwarzbauer, Morrisey, & Haase, 1996; Warach et al., 1994; Ye et al.,
1996). Thus, unlike functional neuroimaging with single photon emission com-
puted tomography (SPECT), positron emission tomography (PET), and tradi-
tional radioligands, MRI perfusion scanning is free of the yoke of radiation, al-
lowing for repeated scanning as well as for scanning in previously excluded
populations like healthy children. This technological advance will likely expand
functional imaging from the binary pretreatment/post-treatment, snapshot mode
of investigation commonly used today into a more dynamic serial tool able to
provide longitudinal analyses of regional brain changes. This serial scanning abil-
ity will perhaps result in a shift of the language used in imaging studies from
"on, off" and "ill, well" to the language of "half-lives" and directions and "vec-
tors of change." We would argue that these new tools are shedding light on how
different brain regions coordinate normal emotions and how regional brain dys-
function might cause mood dysregulation resulting in clinical depression and
mania.
Another important imaging development that will likely reshape functional
neuroimaging research into emotion is the new ability to noninvasively stimu-
late brain tissue with powerful hand-held electromagnets, a field called tran-
scranial magnetic stimulation (TMS) (George, Lisanby, & Sackeim, 1999b;
George, Wassermann, & Post, 1996c). One of the more profound difficulties with
functional neuroimaging is determining whether a signal observed on an image
is related to a behavior or disease in question. Noninvasive but direct stimula-
tion of brain regions in awake human subjects while measuring changes in be-
havior or emotion is an important advance in emotion research. Later in this chap-
Neuroimaging Approaches to the Study of Emotion 109
ter we discuss several of the initial pilot studies using TMS to induce mood
changes in healthy controls as well as in patients with depression. Furthermore,
we describe developments in merging the new technology of transcranial mag-
netic stimulation with conventional neuroimaging. Combining transcranial mag-
netic stimulation with neuroimaging is an important new chapter in the evolu-
tion of the understanding of brain function, particularly the neural correlates of
emotion (George et al., 1999c).
The Need for Understanding Above and Below the

Level of the Regional Circuit
Several other concepts and caveats are important to bear in mind when assess-
ing functional imaging studies. First, psychiatric conditions in general, and emo-
tion research in particular, challenge researchers and clinicians to simultane-
ously integrate information from multiple conceptual levels to explain and
understand these processes and illnesses. Models of mood and emotion regula-
tion must account for genetic factors of disease susceptibility and temperament
while also integrating knowledge about the effects of family, cognitive, and
pharmacological therapies. Functional neuroimaging studies focus attention at
the level of regional neuroanatomical defects. Obviously, this is not the total
answer or method to understanding mood-related illnesses or even normal mood
regulation in health. Eventually, modern psychiatry and psychology must inte-
grate knowledge from diverse conceptual levels to fully understand the com-
plexity of such behaviors as "emotion" and such neuropsychiatric conditions as
"mood disorders."
Second, understanding the distinction between overt brain structural abnor-
malities and brain dysfunction is critical in conceptualizing mood regulation
and dysregulation. In the 1860s, the British neurologist John Hughlings Jack-
son noted that abnormal brain function is not always associated with aberrant
brain structure (Jackson, 1874). When dealing with patients with focal epilepsy,
he noted that even when brain structure was grossly normal, abnormal seizure
discharges could cause behaviors to temporarily disappear (e.g., the ability to
move an extremity) or even bring out emergent properties (e.g., hallucinations
or auras) (Jackson, 1873; Jackson & Stewart, 1899). Thus, problems in behav-
ior (or function) could exist in the setting of grossly normal structure. In pri-
mary mood disorders, visually apparent structural abnormalities are generally
absent in most individuals, although studies of groups of mood disorder patients
have revealed structural differences in the prefrontal and temporal cortices (see
Robinson & Manes, Chapter 10, this volume). Therefore, mood disorders, like
primary generalized epilepsy (which lacks macroscopic cerebral lesions), may
belong to a class of neuropsychiatric diseases with abnormal brain activity de-
I I0 BACKGROUND AND GENERAL TECHNIQUES
spite grossly normal structure. In epilepsy, the electroencephalogram has helped

to legitimize the disease as a medical illness of the brain (Engel, 1989; Temkin,
1945). The new functional imaging tools discussed below (SPECT, PET, func-
tional MRI [fMRI], and TMS) are now further destigmatizing the primary mood
disorders by revealing abnormal regional brain function despite generally nor-
mal structure.
Finally, most functional imaging tools rely on the fact that brain regions that
are more active use more glucose for energy consumption and also receive more
blood flow. Most researchers also assume that blood flow and energy metabo-
lism are coupled (Sokoloff, 1978). For example, while reading this chapter, the
regions in your brain involved in processing visual information and synthesizing
language are more active than they were before you began reading. Those acti-
vated regions thus use more glucose for energy than when you are not reading,
and they receive more blood flow. These assumptions of increased blood flow
and glucose use with greater neuronal activity serve as the background for most
functional imaging studies. The functional image is, however, unable to deter-
mine exactly what a specific brain region is doing when it is activated. That is,
is the brain region excitatory or inhibitory on other brain regions, and is it caus-
ing or inhibiting a behavior? In addition to this thorny issue, other problems are
present in the interpretation of functional imaging studies.
What Does the Signal From Functional Imaging

Actually Mean? Epistemological Caveats
Neuroscience operates under the assumption that behavioral events are mediated
by neuronal events. This assumption is part of the larger assumption that char-
acterizes modern science—that all events have physical causes (as opposed to
nonmaterial causes, like ghosts, goblins, or souls). What follows from this is that
every event occurs within a chain of events; every cause has a cause of its own.
Notwithstanding the difficulties involved in determining that some neuronal ac-
tivity is actually part of the causal chain of the behavior rather than being merely
correlated with it (see, for example, the later discussion of TMS), there is still
the problem of the appropriate level on which to assign causality. Often within
the field of neuroscience, one assumes that a behavior is caused by some struc-
tural and/or functional problem with some neuronal group. For that behavior that
has as its cause a neuronal event, however, we may still consider the cause of
that neuronal event. Consider the causal chain: John pokes Mary, setting off a
neuronal event that results in Mary's behavior of becoming angry. What is the
cause of Mary's anger, the neuronal event or John's poking at her? The issue at
stake is the appropriateness of stopping at the neuronal group in the chain of
causality. The limitations we have in how to control behavior (i.e., where we can
intervene in the causal chain) may help to answer this question, but at this point
Neuroimaging Approaches to the Study of Emotion 11 I
in interpreting signals in neuroimaging studies, one should be cautious in the as-

signment of causality.
Most neuroscientists using functional imaging skirt these philosophical issues
by performing studies and then reporting the results in a strictly observational
manner. For example, if we perform a PET study and the amygdala has increased
blood flow during a drug-induced panic attack and we simply report these two
things (increased amygdala signal and panic), then we have skirted the difficult
but very important issue of exactly how the brain and the behavior relate. Most
modern models of the brain basis of emotion assume that emotions are reflected
in activity in a distributed neural network, comprised of several brain regions,
with perhaps each module performing a subpart of the emotion (e.g., interpret-
ing external events; see also Buck, Chapter 2; Ochsner & Schacter, Chapter 7;
and Adolphs & Damasio, Chapter 8, this volume). Thus, within the realm of the
philosophy of mind, most modern neuroscientists working with functional imag-
ing would be classified as either functionalists or reductive materialists. Func-
tionalists would say that the behavior arises from activity within the neural net-
work (Churchland, 1984). They would allow for the possibility that complicated
networks comprised of things other than neurons (e.g., computers) could also
produce the behavior. In other areas of neuroscience, such as visual processing,
this has largely happened as there are computers with complex pattern recogni-
tion capabilities. Reductive materialists would also say that the behavior arises
from the activity within the network. Thus, in the example above, panic is caused
by the activity in the amygdala. Emotions can be strictly mapped onto brain
events, and only neurons can produce some behaviors such as emotions or con-
sciousness.
Finally, there are eliminative materialists, who would agree that emotions and
behaviors are strictly reducible to brain activity. They would add that, in many
areas of science (e.g., physics, astronomy), as knowledge advanced, the descrip-
tive language used was also radically changed (e.g., we no longer talk about the
ether in the universe). In the field of emotion research, they would argue that as
neuroscience advances, the terms we now use (happy, sad, fear) will likely be
modified or discarded and replaced with more precise language (George, 1987;
Rorty, 1971).
Thus, by interpreting functional imaging studies in a strictly observational
mode, one can temporarily avoid complex issues of mind-brain function. In in-
terpreting the results, however, most scientists are forced to grapple with the
deeper issues of brain-behavior relationships. Most functional imaging studies
today are performed within the paradigm of reductive materialism and attempt
to determine the actual neural network associated with a behavior. Bearing these
important concepts and assumptions in mind, one can properly begin to review
the various techniques now available for noninvasively imaging the living, work-
ing human brain.
DESCRIPTIONS AND EXPLANATIONS OF FUNCTIONAL

IMAGING TECHNIQUES, WITH BRIEF EXAMPLES
Structural Scans: Computed Tomography and

Magnetic Resonance Imaging
The current revolution in neuroimaging technology began with the development by

Hounsfield and others of the ability to sample gamma-ray emissions in a circular or
tomographic way using the new power of computers. This key advance, sampling
radioactivity in a circular way and then reconstructing it with computers to provide
an image of the head, is the basis for computed tomography (CT), SPECT, PET, and,
to some extent, MRI. CT scans are like traditional x-rays in that one emits a beam
and then samples how it is distorted as it passes through the brain before being de-
tected on the other side of the ring around the patient's head. This is done in a 360°
arch around the head and then reconstructed. CT thus involves radiation, and is poor
at resolving structures in the brain stem or posterior fossa. Conventional MRI in-
volves sampling the degree to which hydrogen ions return to their normal configu-
ration after a transient but powerful magnetic pulse (Cohen & Bookheimer, 1994).
Thus, MRI involves no radiation and has remarkable resolving power (on the order
of 1-2 mm). It is also very good at imaging structures surrounded by bone, such as
the posterior fossa.
Functional Neuroimaging: Single Photon Emission Computed

Tomography, Positron Emission Tomography, and
Functional Magnetic Resonance Imaging
In contrast to CT and traditional MRI, which image the structure of the brain, sev-
eral techniques have been developed recently with the power to look at brain Junc-
tion. As discussed above, brain structure does not equal function, and vice versa
(Jackson, 1873; Taylor, 1958). That is, structural brain damage, such as a tumor,
can produce either obliteration of the function normally subserved by that portion
of the brain, or it can heighten the function of that portion of the brain (e.g., in the
case of a seizure discharge [Jackson, 1874]). Additionally, one can have normal
brain structure (at least to the limit of current technology) and have markedly ab-
normal function (i.e., areas of the brain that are normal structurally but are "off
line" functionally). This commonly occurs following cortical strokes where the
contralateral cerebellum is hypofunctional on PET or SPECT images even though
it is structurally intact, a phenomenon referred to as cerebellar diaschisis (George
et al., 1991). We now review these functional imaging tools (Table 5.1).
Quantitative Electroencephalograms
Electroencephalography (EEG) is perhaps the oldest of the techniques available

for "imaging" brain function. An EEG records brain electrical activity, which
Table 5.1. Comparison of Several Functional Imaging Tools
IONIZING SPATIAL TEMPORAL
METHOD IMAGES COST AVAILABILITY RADIATION RESOLUTION RESOLUTION
qEEG Electrical activity Low Wide No Poor, 3-4 cm Fast, milliseconds

PET Flow (15O), metabolism Expensive Very limited Yes 5-7 mm 1-3 minutes
(FDG), or specific
ligands
SPECT Flow (HMPAO) or Moderate Wide Yes 5-7 mm 1-2 minutes
specific ligands
fMRI Flow or deoxyhemoglobin Moderate Limited No 2-3 mm Milliseconds
to oxyhemoglobin
MR spectroscopy H Moderate Limited No 5-7 mm Seconds
Li
PO4
Fl
Magnetoencephalography Magnetic activity Expensive Very limited No Poor Fastest,
milliseconds
TMS Cortical representation Low Limited, but No 2-3 mm Milliseconds
expanding rapidly
I14 BACKGROUND AND GENERAL TECHNIQUES
arises from the combined activity of brain neurons, at the level of the skull. The
patterns of electrical activity over different brain regions reflect brain activity.
EEG is temporally very precise (on the order of milliseconds) but is spatially
very poor, even with many surface leads or electrodes. Furthermore, in addition
to being spatially crude at the brain surface, it is unclear where the majority of
the brain activity arises that comprises the EEG pattern. Several studies have
now attempted to examine the relationship between surface EEG activity and
regional brain activity (Parekh et al., 1995; Wheeler, Davidson, & Tomarken,
1993). Because of the problems with spatial resolution, many researchers have
largely ignored EEG as an investigative probe. Several researchers, however,
have used complex techniques to quantify the EEG patterns (quantitative
EEG [qEEG]) and are using this as a tool for the study of emotion (Davidson,
1994; Leuchter et al., 1997; see also Davidson & Henriques, Chapter 11, this
volume).
Single-Photon Emission Computed Tomography: Perfusion and Ligand
SPECT involves the peripheral injection into a vein of a radiotracer, which then
travels into the brain and is deposited into neurons and glia (George et al.,
1991). The gamma rays (or photons) that these radiotracers emit are then de-
tected by rotating cameras and reconstructed into a three-dimensional image.
Different SPECT radiotracers bind to brain structures and have different half-
lives, which determine when the image can be acquired. A popular current
tracer is 99mTc-hexamethyl propylene amine oxide (HMPAO), which distrib-
utes to the brain in a fashion roughly equivalent to blood flow (Devous et al.,
1986; Ell, Cullum, & Costa, 1985). The tracer can be injected when the patient
is anywhere in the hospital or in a research laboratory and then "sets" within
the active brain regions within the next 2-5 minutes. Patients can then be trans-
ported to the nuclear medicine suite for actual image acquisition. If necessary,
tranquilizing medications can be given to sedate the patient for scanning that
will not affect the actual image acquired, as the perfusion pattern has already
been deposited. This ability to inject while subjects are away from the nuclear
medicine suite and outside of the actual camera makes SPECT imaging par-
ticularly useful for studying diseases such as epilepsy or mania or for inject-
ing tracer in naturalistic settings for emotion activations. As reviewed above,
those areas of the brain that are more active demand either more blood flow
(the basis of perfusion SPECT, 15O PET, and echoplanar BOLD fMRI) or more
glucose (the basis of fluorodeoxyglucose [FDG] PET) (Sokoloff, 1977, 1978).
Functional images thus change as a result of alterations in brain activity due
to differences in the subjects' behavior during the scan.
Migliorelli, Starkstein, and colleagues have used SPECT injections in acutely
Neuroimaging Approaches to the Study of Emotion 1 15
manic patients who could not have been scanned without sedation (which would
then unfortunately affect the functional image). They injected the tracer into
the manic subjects when the subjects were away from the camera, and the tracer
deposited in the brain. They were then able to sedate the subjects so that they
could sit still for the scanning uptake without affecting the picture of brain ac-
tivity, which reflected activity during the moments around injection. Consis-
tent with a valence model of mood regulation, Migliorelli, Starkstein, and col-
leagues have found relative right temporal hypoactivity during mania
(Migliorelli et al., 1993) (see also Robinson & Manes, Chapter 10, this vol-
ume). Recently in our laboratory at the Medical University of South Carolina,
we used this ability of SPECT perfusion imaging to be injected when away
from the camera to image brain activity while subjects were being stimulated
with TMS over the left prefrontal cortex (George et al., 1999d; Stallings et al.,
1997). Because of a concern that the presence of a TMS coil within a PET or
SPECT camera might produce an artifact, we were able to stimulate when away
from the camera and still image brain activity at that moment (Fig. 5.1) . This
study demonstrates the possibility of perhaps using TMS to activate discrete
neural circuits involved in emotion and then image the brain activity using
SPECT.
Figure 5.1. Perfusion SPECT results from eight healthy adults. The maps represent brain
regions that were significantly different in activity from baseline to the task condition in
which subjects were receiving intermittent high-frequency TMS over the left prefrontal
cortex. The areas of peak significance (P < 0.01) are mapped onto a rendered MRI. Dur-
ing stimulation, there is decreased activity at the coil site and in the cingulate gyrus (top).
There was increased activity in the brain stem during stimulation.
Positron Emission Tomography
Blood flow
Positron emission tomography involves the peripheral injection of radiotrac-
ers that, when they degrade, emit positrons. These are highly unstable particles
that travel a short distance and then collide with an electron. This reaction re-
leases two photons travelling in exactly the opposite direction (180° apart). These
photons are then detected by rotating cameras outside of the head and computer
reconstructed. In PET, as opposed to SPECT, the cameras are instructed to in-
clude for final analysis only those particles that are recorded simultaneously in
a camera and in its 180° counterpart (called coincidence detection), thus enabling
a more precise reconstruction of exactly where the photon originated. This, in
general, gives PET a higher image resolution than SPECT (see Table 5.1). Most
PET imaging in normal and pathological moods has been done with labeled glu-
cose (18FDG) or oxygen (15O) in the form of water. These compounds have to
be produced in a nearby cyclotron, which adds greatly to the cost as well as lim-
its the availability of these types of scans. Additionally, both PET and SPECT
offer the possibility of imaging more selective pharmacological systems in the
brain with specific radiotracers. Examples with SPECT include dopamine re-
ceptors (George et al., 1994b; Ring et al., 1992), acetylcholine receptors, and
benzodiazapine receptors with flumazenil. To date, PET studies with specific lig-
ands have imaged dopamine, opiate, and acetylcholine receptors. PET radiotrac-
ers have also been made by attaching a labeled carbon to various neuroactive
compounds such as labeled deprenyl or fluoxetine. PET 15O image acquisition
takes approximately 1-5 minutes, with FDG requiring on the order of 30 min-
utes. Thus, the differences between SPECT and PET are simply in their use of
different tracers (photons, SPECT; positrons, PET) and cameras (photon colli-
maters, SPECT; coincidence detection, PET). The need for nearby production of
positron-emitting tracers will likely continue to make PET more expensive and
less available than SPECT. Advances in camera design may allow combined
PET/SPECT cameras or SPECT cameras that can create metabolic images with
FDG.
15
O PET has been used frequently in studies designed to elucidate the brain
basis of emotion. 15O deposits in the brain within 2-5 minutes in proportion to
blood flow and then quickly washes out, leaving no radiation, so that another
scan can be performed 12 minutes later with another injection. Depending on the
camera and safety limits, one can acquire 12 or more separate scans in an indi-
vidual within a 2-hour imaging session.
Using this technique, Pardo, Pardo, and Raichle (1993) initially found that left
anterolateral prefrontal cortex activity increases when subjects are asked to think
sad thoughts. As an added task at the end of a scanning session, subjects were
asked to close their eyes and imagine a sad event. This initial study suffered from
the lack of a control task with a memory component. Shortly thereafter, work in
our own laboratory with 11 healthy adult women demonstrated that transient sad-
ness is associated with increased activity in the left anterior cingulate, left me-
dial frontal cortex, and the anterior temporal lobes bilaterally (George et al.,
1995a) (Fig. 5.2). We employed a combined method of inducing the mood state
neuropsychologically by having the subjects recall a personal emotional event
and then having them examine mood-appropriate faces during 15O injection. The
control task involved the subjects remembering a neutral event and examining
neutral faces. Others have now replicated and expanded on this work (Lane et
al., 1997). Interestingly, the brain regions activated vary not only as a function
of the mood (happy, sad, neutral) but also by how the mood state was achieved
(Reiman et al., 1997). In general, emotional states achieved when subjects recall
affectively laden past events involve more of the hippocampus, whereas exter-
nally generated emotions (e.g., with films, videos, or pharmacological challenges
like procaine) are more likely to involve the amygdala.
Following up on our initial findings of sadness induction in adult women, we
explored potential sex differences in the brain regions activated during emotional
states. Men are less likely than women to experience disorders of mood or anx-
iety. We thus wondered if sex differences exist in the ability to self-induce tran-
sient emotional states (sadness or happiness) and also if regional cerebral blood
Figure 5.2. Statistical parametric maps of brain regions in 11 healthy adult women. Re-
gions were activated during a state of self-induced transient sadness (P < 0.01 for dis-
play). Note the activity in the medial prefrontal cortex and other anterior paralimbic struc-
tures. SPM, statistical parametric mapping; VAC, anterior commisure; VPA, posterior
commisure.
flow (rCBF) would differ between men and women either at rest or during tran-
sient emotional states. In a follow-up study, we scanned ten adult men and ten
age-matched women, all healthy and never mentally ill, with PET and H215O at
rest and during happy, sad, and neutral states self-induced by recalling affect-
appropriate life events and looking at happy, sad, or neutral human faces (George
et al., 1996a). There were no differences between men and women in the sub-
jective ratings of difficulty, effort required, or degree of happiness or sadness in-
duced. Women activated a significantly wider portion of their limbic system than
did men during transient sadness, despite similar changes in mood. Although men
self-induced transient emotional states to the same degree as women, women had
more extensive rCBF changes than men (eight times as many voxels) in anterior
limbic regions during transient sadness. The reason for these sex differences in
rCBF, both at rest and during the transient emotional states, remains unclear. Po-
tential sex differences with respect to emotion are, however, important and should
be kept in mind in most functional imaging studies (Baxter et al., 1987; Shay-
witz et al., 1995).
15
O PET can also be used to examine how our brains understand the emotional
content of the external world. For example, important clues about the emotional
states of others are conveyed in noncontent aspects of speech, referred to as
prosody. In collaboration with Drs. Heilman, Bowers, and Bauer of Florida, we
designed an 15O PET study of 13 healthy volunteers. These subjects activated
bilateral prefrontal cortex (left more than right) when listening for the emotional
prepositional content of a sentence. In contrast, when listening to the same set
of sentences but responding based on the emotional prosodic content, they acti-
vated the right prefrontal cortex and insula. The results of this first PET study
of emotional prosody agree with those in a substantial lesion and neuropsycho-
logical literature that implicates right lateralization of prosody (George et al.,
1996b).
Metabolism
In addition to measuring blood flow, PET can be used to measure the meta-
bolic activity of the brain by tagging glucose with a radiotracer (typically
18
FDG) and calculating how much of this tracer deposits in the brain. Like
SPECT perfusion tracers, FDG can be infused away from the actual PET cam-
era, allowing some flexibility. Because of the uptake time of 20-30 minutes
and the long half-life, however, FDG PET is not an ideal instrument for acti-
vation studies, although some have used paired FDG in selected instances in
which one scan serves as a baseline for comparison with a task in the second
scan (Bremner et al., 1996; Wu et al., 1992). More typically, FDG PET has
been used as a baseline measure to compare across groups of mood-disordered
subjects (Baxter et al., 1985, 1989).
Neuroimaging Approaches to the Study of Emotion I19
Functional Magnetic Resonance Imaging
The newest group of functional neuroimaging technologies is functional MRI

(David, Blamire, & Breiter, 1994; Kwong et al., 1992; Rosen et al., 1994;
Stehling, Turner, & Mansfield, 1991; Turner et al., 1991). Under this general
heading are several techniques that use the power of MRI systems to image func-
tional brain changes (rather than brain structure). One method is to inject a bo-
lus of a magnetic compound and watch its distribution through the brain over a
short time (generating a perfusion image of blood flow) (Rosen et al., 1991). This
technique is easy to perform but requires an intravenous bolus injection, is lim-
ited in the number of boluses per individual due to kidney toxicity of the trac-
ers, and only provides information about relative regional activity (not absolute
flow). Alternatively, other groups are using a method of magnetically tagging
hydrogen atoms in water as they course through the bloodstream and then imag-
ing the same atoms as they perfuse through the brain (called spin labelling and
inversion recovery) (Warach et al., 1994). This method is described in greater
detail below.
Blood oxygen level-dependent functional magnetic resonance imaging

The most popular method of using MRI to image brain function capitalizes on
the fact that oxyhemoglobin is nonmagnetic, whereas deoxyhemoglobin is para-
magnetic. Thus brain areas with high demand will have a different ratio of oxy-
hemoglobin to deoxyhemoglobin and will thus give off a different magnetic sig-
nal (a technique that is blood oxygenation level dependent [BOLD]) (Turner et
al., 1991). By taking very fast images (on the order of an image or more per
second) using a rapid sampling technique (echoplanar acquisition) and high-
performance magnetic gradients, one can rapidly image the differences between
activity at rest and activity during a specific behavior and generate enough im-
ages to perform statistical analyses within a given individual. By acquiring struc-
tural MRI scans in the same slices as the functional data, one can precisely map
regional brain changes without having to use morphing programs. This technique
is ideally suited for tasks and behaviors that can be rapidly stopped and started,
such as language, vision, and memory (David, Blamire, & Breiter, 1994). The use
of this technique in studying emotion is hampered by the slow and variable on-
set of emotions as well as their inability to be quickly reversed. Some investiga-
tors have succeeded in using this tool to examine brain changes during emotional
processing of stimuli such as faces (Breiter et al., 1996; Whalen et al., 1998).
Echoplanar BOLD fMRI is well suited to examining changes in cortical blood
flow during precise cognitive tasks. When studying the brain basis of emotion,
however, one is often interested in imaging structures at the base of the brain
such as the orbitofrontal and medial temporal cortex. Echoplanar acquisition is
susceptible to artifacts in areas where brain is near air, such as the air in the mas-
toid sinus. This is a perplexing problem with this technique in the study of the
brain basis of emotion. Newer imaging sequences and the use of coronal slices
has largely eliminated this susceptibility artifact; however, BOLD fMRI still re-
quires precise on/off task cycling, which may be difficult in studies of induced
emotions. The newest advances in BOLD fMRI are the use of a single event to
generate the signal, which may expand this technique's use in emotion research
by eliminating the need for on/off tasks as well as the concerns about movement
during the task (for a general overview of this area, see Davidson & Irwin, 1998).
Serial perfusion magnetic resonance imaging scanning

One of the main impediments to serial functional imaging of mood disorders
has been the limitation imposed by radiation safety limits with SPECT and PET.
This radiation limit has severely hampered the ability to understand mood dis-
orders not simply as episodes that clearly start and stop, but over time in regional
brain activity through a mood cycle. Several groups have begun using the new
imaging method of quantitative spin labeling and inversion recovery perfusion
functional MRI (pfMRI) (Warach et al., 1994). This technique has been used in
preclinical models studying cerebral perfusion or rCBF (Bohning et al., 1996)
and has been shown in healthy controls to repeatedly and consistently measure
cerebral perfusion (Bohning et al., 1997b). pfMRI involves neither an injection
nor radiation exposure, and therefore multiple measures per subject can be done.
Furthermore, it can quantitatively measure rCBF, which cannot be done with per-
fusion SPECT and requires an arterial line with PET scanning. The entire scan-
ning sequence initially took about 30 minutes per slice, but we have recently re-
duced this to 5 minutes per slice, moving ever closer to achieving a scan time
that will work in an acute clinical setting.
We have recently used pfMRI to serially scan rapid-cycling bipolar affective
disorder (BPAD) patients as they progress through their mood cycle (Spur et al.,
1997). As a comparison group, we have also scanned age-matched and sex-
matched controls on the same day in the same scanner, using identical techniques.
These studies are being used to test our hypothesis that BPAD mood disorder
subjects, when depressed, have increased activity in the right anterior temporal
and insular regions and that during mania the same areas are relatively hypoac-
tive. We are also keenly interested in whether there is a temporal dissociation or
lag between clinical symptoms or phenomenology and changes in regional rCBF.
That is, clinical symptoms and improvement may precede rCBF changes. To date,
we have found that there is a complex association between clinical mood state
and global brain activity on the day of the scan (Speer et al., 1997).
Figure 5.3 shows the relationship between global gray matter perfusion and
mood over time in one subject. Note that, although mood and global rCBF roughly
correlate, there are exceptions when global perfusion precedes or lags behind
Figure 5.3. The relationship between global brain activity and mood state is complex,
with several earlier reports indicating a positive correlation between global brain activity
and mood (more activity in mania). Using the new technique of perfusion functional MRI,
we have been directly addressing this issue. Shown are the global perfusion rates in the
middle of the brain (horizontal line) (open squares) as a function of mood state.
clinical ratings. These pilot studies, with a novel noninvasive technology that
permits measurement of absolute brain perfusion, are perhaps yet another win-
dow into the brain of BPAD subjects, allowing for the first time serial assess-
ment of the regional brain changes associated with mood cycling. This advance
hopefully will allow better examination of regional brain changes over time and
of how they relate to clinical symptoms.
Magnetic resonance spectroscopy

Magnetic resonance spectroscopy (MRS) uses modified structural MRI scan-
ners to study resonance spectra of compounds containing paramagnetic (odd
atomic number) elements. Proton or 1H MRS allows determination of lactate,
glutamate, aspartate, gamma-aminobutyric acid, creatinine, choline, and N-acety-

laspartate. Lithium (7LI) and fluorine (19F) MRS can assess cerebral concentra-
tions of lithium and fiuorinated drugs, respectively. Phosphorus (31P) MRS al-
lows determination of high-energy phosphates (ATP), intracellular pH, free
magnesium, and some phospholipids, including phosphomonoesters (putative cell
membrane "building blocks") and phosphodiesters (putative cell membrane
breakdown products). Spectroscopy has to date been used by only a few groups
to study mood or emotion (Cohen, Renshaw, & Yurgelun-Todd, 1995; Dager et
al., 1995). Thus far, only a few groups interested in psychiatry or psychology
have effectively tackled the daunting technological hurdles behind MRS, which
range from radiofrequency coil designs to software packages. Theoretically,
MRS, with the ability to noninvasively image chemical changes such as brain
ATP, could prove to be the ultimate functional imaging tool.
Transcranial Magnetic Stimulation
Another recent technological development that will likely impact heavily on the
field of functional imaging and emotion research is TMS. With the ability to non-
invasively activate neurons, TMS offers the promise of overcoming the formidable
barrier of the skull, with real-time noninvasive probing and testing of neuronal cir-
cuits and behavior. Transcranial magnetic stimulation uses the principle of induc-
tance to convey electrical energy across the scalp and skull without the painful side
effects of direct percutaneous electrical stimulation (for reviews, see George,
Lisanby, & Sackeim, 1999b; George, Wassermann, & Post, 1996c). It involves
placement of a small coil of wire on the scalp and a very powerful current passing
through it (Barker, Jalinous, & Freeston, 1985; Roth et al., 1991; Saypol et al., 1991).
A magnetic field is produced that moves unimpeded through the tissues of the head.
The magnetic field, in turn, induces a much weaker electrical current in the brain.
The shape of the electromagnet coil is important because different coil shapes
produce different magnetic fields (Cohen et al., 1990; Murro et al., 1992). The
main differences are in the size and focality of the magnetic field. For instance,
so-called butterfly or eight-shaped coils consist of two loops of windings that in-
tersect in the middle. The magnetic field is maximal at the intersection and weaker
elsewhere. This allows fairly focal stimulation of the brain and has allowed the
technique to be used for cortical mapping (Bohning et al., 1997a; Pascual-Leone,
Grafman, & Hallett, 1994; Pascual-Leone et al., 1995; Roberts et al., 1997; Wasser-
mann et al., 1992; Wilson, Thickbroom, & Mastaglia, 1993). The stimulators and
coils in production today develop about 1.5-2 Tesla at the face of the coil and are
able to activate neurons 1.5-2 cm from the surface of the coil in the cortex (Ep-
stein et al., 1990). Activation of neurons deeper in the brain may be possible with
solid-core coils, formed by coiling wire around a bar of a paramagnetic material
such as iron (Davey, Cheng, & Epstein, 1991; Weissman, Epstein, & Davey, 1992),
or with other combinations of coils (Bohning, personal communication). Even

though conventional TMS can directly activate only cortical neurons, it affects
cells at some distance from the stimulation site through trans-synaptic connec-
tions. Preliminary evidence for trans-synaptic effects within the brain comes from
changes in hormones induced by stimulation (George et al., 1996a) and wide-
spread changes in brain activity during TMS detected with functional imaging
techniques (discussed below) (Bohning et al., 1998a; George et al., 1995b; Kim-
brell et al., 1997; Paus et al., 1997; Stallings et al., 1997; Wassermann et al., 1997).
Transcranial magnetic stimulation-induced changes in normal mood

One long-standing model of emotion regulation has been the valence model
of mood, which postulates that whereas the left hemisphere mediates positive
emotions (e.g., happiness), the right mediates negative emotions (anger, fear, dis-
gust, anxiety, sadness) (Ross, Homan, & Buck, 1994; Sackeim & Gur, 1978;
Sackeim, Gur, & Saucy, 1978). An individual's mood at any given time thus re-
flects the relative balance of the input of the two hemispheres. Either temporar-
ily or permanently disabling one hemisphere would allow the other to act in an
unbalanced manner (see Robinson & Manes, Chapter 10; Davidson & Henriques,
Chapter 11; and Lisanby & Sackeim, Chapter 18, this volume). The valence hy-
pothesis, while supported by many studies, is by no means proven, and several
studies have yielded results inconsistent with this theory (House et al., 1990;
Sharpe et al., 1990; for a critical review, see Sackeim, 1991). In addition, only
a weak plurality of functional imaging studies in mood disorder patients support
lateralized dysfunction.
We first sought to directly test the valence theory of mood by employing repet-
itive TMS (rTMS) to temporarily excite (and then disable) prefrontal cortex and
observe the effects on mood (George et al., 1996d). Using rTMS over the right
or left prefrontal cortex of ten adult healthy volunteers on different days, we dis-
covered that left prefrontal stimulation caused an increase in self-rated sadness,
while right stimulation caused increases in happiness (for stimulation, we used
a figure-eight coil, 120% of motor threshold [MT], 5 Hz for 10 seconds, 2 min-
utes of rest, on and off ten times, a total of 20 minutes of stimulation, and 500
stimuli per session). This study confirmed and extended the initial study of
Pascual-Leone, Catala, and Pascual (1996a), who had stimulated different brain
regions within the same day and achieved roughly the same results, but signifi-
cant mood effects were seen within 30 minutes of stimulation at higher frequency,
shorter intertrain interval parameters (110% MT, 10 Hz for 5 seconds, 25 sec-
onds apart, for ten trains). This TMS-induced mood effect appears to be specific
to prefrontal stimulation, although active nonprefrontal sites were only explicitly
tested in the initial study of George et al. (1996d).
In a recent follow-up study using a more fastidious design, we stimulated a
different (from those in earlier study) group of controls with selective prefrontal
stimulation on one day and entire hemisphere stimulation on another (Martin et

al., 1997). During selective prefrontal stimulation in nine healthy controls over
the right hemisphere, self-rated happiness increased, whereas left prefrontal stim-
ulation resulted in increased sadness (80% MT, 20 Hz, 2 sec/min 20 times over
20 minutes). Entire hemisphere stimulation with a larger nonfocal coil and with
identical parameters and ratings caused no significant change in mood (see
Fig. 5.4). Interestingly, we also found that right stimulation caused significant
increases in anxiety. Although the results are provocative, caution is clearly
needed in the interpretation of these pilot studies in a new field with small sam-
ple sizes.
Use of repetitive transcranial magnetic stimulation as an antidepressant

(a therapeutic probe of pathological mood)
Converging evidence from SPECT, PET, and qEEG points to hypofunction of
the left prefrontal cortex in clinical depression (discussed above). Reasoning from
these imaging studies, as well as from the rTMS mood effects in healthy con-
trols and other initial pilot treatment studies (Grisaru et al., 1994; Hoflich et al.,
1993; Kolbinger et al., 1995), we questioned whether daily prefrontal rTMS might
improve mood in depressed subjects. We wondered whether one might be able
to stimulate subconvulsively over prefrontal cortex and achieve an antidepres-
sant effect. We initially studied the immediate effect of right versus left prefrontal
rTMS in medication-resistant patients. Paradoxically and in direct contrast to the
results obtained with healthy volunteers, in whom right prefrontal stimulation
caused subtle but statistically significant increases in self-rated happiness, right
prefrontal stimulation in the severely depressed adults resulted in marked in-
creases of anxiety and worsening mood.
We therefore performed daily left prefrontal rTMS in six highly medication-
resistant depressed inpatients. Depression scores significantly improved for the
group as a whole (Hamilton Depression Scores decreased from 23.8 [4.2 SD at
baseline] to 17.5 [8.4 SD] after treatment). Two subjects showed robust mood
improvement, which occurred progressively over the course of several weeks. In
one subject, depression symptoms completely remitted for the first time in 3
years. We concluded that daily left prefrontal rTMS was safe and well-tolerated
and might alleviate depression (George et al., 1995b).
Dr. Pascual-Leone and colleagues (1996) next used a double-blind placebo-
controlled design and reported that left prefrontal rTMS for 5 days (at 90% MT,
10 Hz, 10 seconds, 1 minute rest, 20 times each morning, 2000 stimuli per morn-
ing, 10,000 per site; 40,000 total per subject) significantly improved mood in 17
psychotically depressed subjects. Stimulation at other sites (e.g., right prefrontal,
occipital) had no effect. Even at these high doses and numbers of stimuli, rTMS
was well-tolerated (Pascual-Leone et al., 1996b).
Immediately after completing our open study in medication-refractory inpa-

tients, we undertook a double-blind placebo-controlled crossover study of daily
left prefrontal rTMS in depressed outpatients (20 Hz, 2 seconds, 1 minute rest,
80% MT, 200 times per day; 800 stimuli per morning; 8000 stimuli per site).
There was a significant improvement in mood as a function of TMS treatment
(George et al., 1997b), although the magnitude of change was not nearly as pro-
found as in the study of Pascual-Leone et al. (1996b). There are now many groups
in the United States and elsewhere using rTMS for investigating and treating de-
pression and exploring the different rTMS parameters (location, intensity, fre-
quency, dosing schedules, diagnostic groups) in rTMS depression treatment tri-
als (for reviews, see George, Lisanby, & Sackeim, 1999b; George et al., 1999a;
Lisanby & Sackeim, 1998). It is unclear what clinical role rTMS might have, if
any, in the treatment of depression. Further work to elucidate normal mood reg-
ulation and how TMS affects different brain areas is crucial.
Combining transcraniai magnetic stimulation with functional imaging

to directly activate, visualize, and test neuronal circuits
As mentioned above, there are many technical issues associated with perform-
ing TMS in a PET, SPECT or MRI scanner. As a first step in this field, after per-
forming a split FDG scan in a depressed patient in an early TMS treatment trial,
we began using techniques in which the tracer uptake is removed from the actual
scanner; the image can then be "developed" later, away from the TMS coil. In
work at the National Institutes of Health, Kimbrell and colleagues (1997) have car-
ried out a split-dose FDG PET study to look at the effects of low-frequency (1 Hz)
TMS over prefrontal cortex. Some preliminary data from this study are shown in
Figure 5.4, demonstrating that, compared with the resting scan, there are global de-
creases in brain metabolism and also regional decreases at the coil site and in the
contralateral medial temporal region (perhaps the amygdala). Several other groups
have also recently demonstrated local and trans-synaptic effects of rTMS (Bohn-
ing et al., 1998a,b; George et al., 1995b; Paus et al., 1997; Stallings et al., 1997;
Wassermann et al., 1997). These studies demonstrate the power of coupling func-
tional imaging with TMS to probe brain function (George et al., 1997a, 1999c).
GENERAL PROBLEMS COMMON TO MOST MODALITIES
Armed with a general understanding of the choice of imaging tools, one can now
understand why different techniques are better suited for investigating different
aspects of mood or emotion. Regardless of the imaging tool, there are several
common problems that confront all researchers in this area. We discuss them
briefly here.
Figure 5.4. Statistical parametric maps of regional brain changes in eight healthy adults
undergoing split-dose FDG PET. In the task condition, subjects received low-frequency
TMS over the left prefrontal cortex. Compared with the control state, global brain me-
tabolism significantly dropped during the prefrontal TMS, which was not seen in a par-
allel study with sham TMS over the same region. Note the decreases in normalized ac-
tivity at the coil site, in the medial prefrontal cortex, and in the contralateral medial
temporal cortex.
Monitoring of Emotion and Choice of an Appropriate Baseline
For any imaging study, measuring emotion is a thorny issue. One main problem
is whether sampling disturbs the mood or emotion. That is, too frequent sam-
pling of a subject's self-rated mood might interfere with the mood induction pro-
cedure. This issue is discussed in more detail elsewhere in this volume. The other
issue is how to integrate psychophysiological measurements like heart rate and
skin conductance into the imaging laboratory. In some environments, such as a
SPECT study in a psychophysiology laboratory, this is trivial. In other situations,
such as with an MRI scanner, this is very complex.
Just as measuring the emotion under study is difficult, it is not easy to deter-
mine the baseline for comparison with the emotional state. For studies with both
healthy and mood-disordered individuals, the comparison is simple. In activation
studies, however, the appropriate baseline is sometimes difficult to achieve. Even
when comparing two groups, the choice of what mental task to have individuals
focus on is also important. In general, groups now have subjects engage in a mod-
erately difficult task, like an auditory continuous performance task, during "base-
line scans." This ensures that the subjects are awake and alert and that the differ-
ences that are detected are less likely to have arisen from different cognitive tasks
during the scan. This area is not settled, however, and there is no true consensus.
Study Design and Statistical Analysis
In general, imaging studies that build on hypotheses generated from other ap-
proaches (lesion studies, brain stimulation, the Wada procedure, and tachisto-
scopic studies) are the most straightforward. The statistical analysis can be lim-
ited to the region under question with a region of interest analysis. When
researchers begin to perform more exploratory studies, however, both the choice
of appropriate study design and the proper statistical analysis becomes less clear.
Depending on the question, one can choose an event-related study (inject tracer
during acute anxiety) or a block design (scan before and after an intervention or
task, regardless of the subjective emotion).
A particularly perplexing problem within the field of functional imaging in-
volves how to appropriately test for statistical significance within or between
groups when numerous brain are compared. With limited comparisons and
hypothesis-driven questions, traditional statistical analyses suffice. Once brain
activity has been pooled and normalized into a common brain space, however,
how can one effectively perform an exploratory analysis that accounts for the
total number of comparisons (typically on the order of thousands)? An entire new
branch of statistics has arisen within the field of functional imaging to deal with
these thorny issues (Friston et al., 1990, 1994). Much as each of the separate
imaging tools has particular advantages and disadvantages for a particular ques-
tion, there are numerous approaches to statistical analysis. Common approaches
to reduce the number of total comparisons involve smoothing of the data (thus
decreasing the independence of each pixel and decreasing the total number of ef-
fectively discrete regions) (Friston et al., 1994), restriction of the initial search
to key regions, or division of the group in half and two separate analyses, with
the first half being exploratory in nature and the second half potentially con-
firming the results in the first half (Fox & Mintun, 1989). All approaches have
their relative advantages and disadvantages.
SUMMARY AND CONCLUSIONS
Functional imaging has recently evolved into a complex area with multiple tech-
niques for investigating brain function. Within the past 20 years, the field has gone
from having only one functional imaging tool (EEG) with poor spatial resolution
to now having a host of different techniques with a variety of specific advantages

and drawbacks. In this chapter, we reviewed many of the common problems as-
sociated with performing imaging studies to examine the neural substrates of mood
and then briefly described the more common imaging tools in use today. Other
chapters in this volume expand on this introduction and provide more in-depth
analyses of the work by many of the leading researchers in this area.
Thus, the field of functional neuroimaging offers much promise in elucidating
the brain basis of mood and emotion. Functional imaging studies, constantly re-
minding us of the inextricable links between the mind and the brain, may finally
put an end to dualistic concepts of mind and emotion separated from brain. They
also offer the potential of forcing us to change our language about emotion into
a more exact, neuroscientifically based discourse. As these techniques are refined
and improved, they will undoubtedly help enhance our knowledge of the brain
basis of emotion.
ACKNOWLEDGMENTS
Dr. George thanks NARSAD, the Stanley Foundation, NIAAA, NIDA, Dupont Pharma, Dantec In-
ternational, Picker International, Solvay, Jansenn, and Lilly for financial support of many of the imag-
ing projects discussed.
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Ill
THEORETICAL PERSPECTIVES
6
Psychological Models of Emotion
KLAUS R. SCHERER
This chapter provides an overview of theories currently discussed in the psy-

chology of emotion and the controversies and research issues they generate. As
should become obvious in this review, many of the fundamental differences
among the models relate to the thorny issue of the definition of the phenomenon
called emotion and its conceptualization and operationalization. Not surprisingly,
the disagreement as to the nature of emotion extends to the problem of delimi-
tation of the psychological states or processes to be studied under this label from
other affective phenomena. We first review the elements of the definition of emo-
tion that seem to show at least some degree of convergence between different
theorists.
DEFINITION AND DELIMITATION OF EMOTION
Although one occasionally encounters the position that organisms are always
emotional, only more or less so, a sizeable number of emotion psychologists
stress the episodic nature of emotion (Ekman, 1992a; Frijda et al., 1991; Scherer,
1993). The fundamental assumption of this position is that a noticeable change
in the functioning of the organism is brought about by some triggering event,
which can be external (such as the behavior of others, a change in a current sit-
137
I 38 THEORETICAL PERSPECTIVES
uation, or an encounter with novel stimuli) or internal (such as thoughts, mem-

ories, or sensations). The emotion episode is supposed to last for a certain dura-
tion and then, with decreasing intensity, to more or less fade away. Therefore, it
is normally easier to identify the onset than the offset of the changed state. The
abruptness of both onset and offset of the episodes are expected to systemati-
cally vary for different kinds of emotion.
One of the major definitional issues is the question of what changes in differ-
ent modalities are necessary and sufficient elements or components of the emo-
tional episode. Although there are theorists who would restrict the use of the term
emotion to a single modality (e.g., Clore [1994] would restrict it to conscious
feelings of changed states), most current theorists subscribe to a multicompo-
nential definition. These components generally include what has been called the
"reaction triad" of emotion, namely, physiological arousal, motor expression, and
subjective feeling. Some theorists extend the scope of necessary components to
include motivational factors such as action tendencies and the cognitive processes
that are involved in evaluating the eliciting events and the regulation of ongoing
emotional processes (Buck, 1985, 1993; Ellsworth, 1991; Frijda, 1986, 1987;
Scherer, 1984a,b, 1993).
Another point of definitional convergence is the assumption that emotions are
normally triggered by internal or external stimuli or events that are of major sig-
nificance to an organism. Thus, emotions have been called relevance detectors
(Frijda, 1986). Relevance detectors require, of course, an evaluation of stimuli
and events with respect to their meaning for the organism. Many theorists agree
that the nature of this evaluation determines both the functional response of the
organism—whether it is directed toward adaptation to or mastery of the event or
situation—and the nature of the organismic and mental changes that will occur
during the emotional episode.
Although there is much discussion of emotions as processes, which implies
rapid changes over time, most theories and research still implicitly refer to emo-
tional states, suggesting relative stability over time. This is mainly because few
theorists have thus far attempted to directly address the nature of the changes oc-
curring in the reaction modalities or in the emotion components during an emo-
tional episode. To underline the unitary character of the emotional episode, I sug-
gest that interdependent and synchronized changes in component processes are
required as a necessary condition for the definition of emotion (Scherer, 1987,
1993).
Combining these elements of a definition of emotion (for which one finds in-
creasing consensus in the literature) yields a working definition for the purposes
of this chapter: emotions are episodes of coordinated changes in several compo-
nents (including at least neurophysiological activation, motor expression, and
subjective feeling but possibly also action tendencies and cognitive processes) in
Psychological Models of Emotion 139
response to external or internal events of major significance to the organism. This

working definition demarcates the coverage of emotion in this chapter from other
affective phenomena that are not dealt with by the models reviewed here. Table
6.1 contrasts emotions thus defined with other affective phenomena on a num-
ber of essential design features (see also Frijda, 1993). It provides a brief defin-
ition with examples of five different types of affective states and traits. The dif-
ferent constructs are then compared on the basis of a matrix of design features
that typically include intensity and duration, the degree of coordination or syn-
chronization of different organismic systems during the state, the extent to which
the change in state is triggered by or focused on an event or a situation, the ex-
tent to which the differentiated nature of the state is due to a process of antecedent
evaluation or appraisal, the rapidity of change in the nature of the state, and the
degree to which the state affects behavior.
Many of the controversies in emotion psychology can be traced to a failure to
clearly distinguish between the different classes of phenomena. General affec-
tive valence or preference should not be treated in the same manner as emotional
episodes, nor should more enduring affective states such as attitudes. For exam-
ple, it is hardly helpful to use the study of simple preferences, such as liking for
certain types of stimuli, to address theoretical issues with respect to the emotion
construct as defined above.1 The confusion between different types of affective
phenomena, rampant in discussions of the psychology of emotion, has unfortu-
nately spilled over into other areas such as neuropsychological approaches where
the label emotion is often used for positive/negative valence of different types of
stimulation. Clearly, one cannot hope to discover the underlying mechanisms un-
less one has first clearly delimited the phenomena one is trying to explain.
Another frequently encountered source of confusion relates to the tendency,
based on popular usage of the terms, to treat emotion and feeling as synonyms.
Although this is standard philosophical practice, it becomes extremely danger-
ous once one attempts to dissect the nature of the components of emotion. In
such attempts it is helpful to define the subjective experiential component of the
emotional reaction as "feeling" or "sentiment." As shown below, confusion be-
tween the phenomenon of emotion as a whole, consisting of several components,
and one individual component, conscious subjective feeling, is responsible for
much of the controversy surrounding the classic James-Lange theory.
This discussion of the definition and delimitation of emotion is concluded with
a strong plea for researchers to avoid definitional confusion of this sort in future
work. The linguistic labels attached to specific types of affective states are not
always helpful. As is true for many other areas of psychology, popular usage of
1
In this sense, Zajonc's insistence (1986) on the independence of affective preferences from "cog-
nitive" processing does not appear to be very pertinent for theories of emotion.
Table 6.1. Design Feature Delimitation of Different Affective States*
BRIEF DEFINITIONS EVENT APPRAISAL RAPIDITY BEHAVIORAL
OF AFFECTIVE STATES INTENSITY DURATION SYNCHRONIZATION FOCUS ELICITATION OF CHANGE IMPACT
Emotion: relatively brief + + —> + + + + +++ +++ +++ +++ +++

episode of synchronized
responses by all or most
organismic subsystems
to the evaluation of
an external or internal
event as being of major
significance (e.g., anger,
sadness, joy, fear, shame,
pride, elation, desperation)
Mood: diffuse affect state, + -» + + ++ + + + ++ +
most pronounced as change in
subjective feeling, of low
intensity but relatively long
duration, often without
apparent cause (e.g., cheerful,
gloomy, irritable, listless,
depressed, buoyant)
Interpersonal stances: + ++ +^»++ + ++ + +++ ++
affective stance taken toward
another person in a specific
interaction, coloring the
interpersonal exchange in
that situation (e.g., distant,
cold, warm, supportive,
contemptuous)
Attitudes: relatively 0 -* + + ++-»+ ++ 0 0 + 0 + +
enduring, affectively
colored beliefs,
preferences, and
predispositions toward
objects or persons (e.g, liking,
loving, hating, valuing,
desiring)
Personality traits: 0 -» + +++ 0 0 0 0 +
emotionally laden, stable
personality dispositions and
behavior tendencies, typical
for a person ( e.g., nervous,
anxious, reckless, morose,
hostile, envious, jealous)
*Symbols indicate the degree to which the features are present, with 0 indicating the lowest (absence) and + + + indicating the highest; arrows indicate hypothetical
ranges.
142 THEORETICAL PERSPECTIVES
some terms has created semantic constructs that are less than optimal for exact
scientific description. The use of a clearly identified design feature approach, as
exemplified in Table 6.1, seems to be more promising in the long run.
HISTORICAL ROOTS OF CURRENT PSYCHOLOGICAL

MODELS OF EMOTION
It is difficult to understand current theories and research objectives in the psy-

chology of emotion—in particular the controversies in the field—without un-
derstanding the historical development of the current models. More than in other
areas of psychology, the work on emotion has been strongly marked by the the-
orizing of a few major thinkers. A few examples of the continuity of some of
the strands of argumentation that are used currently in debates about emotion are
highlighted here.
Plato and the Cognition-Emotion Debate
Plato's suggestion that the soul has a tripartite structure, composed of the sepa-
rate and opposing areas of cognition, emotion, and motivation, has influenced
philosophers and psychologists for over two millennia. Aided by the "faculty"
doctrines of eighteenth and nineteenth century philosophy, the urge to postulate
separate systems for cognition, emotion, and motivation has been a near-constant
source of controversy in the psychology of emotion (Hilgard, 1980). This ancient
debate has been revitalized in recent years under the name of "cognition-emotion
debate" (Lazarus, 1984a,b; Leventhal & Scherer, 1987; Zajonc, 1980, 1984a,b).
Fifty years after Plato formulated the doctrine of the tripartite soul, Aristotle ar-
gued for the impossibility of such a separation and for the assumption of an in-
teraction between the different levels of psychological functioning (Fortenbaugh,
1975). Echoing Aristotle, many modern theorists are trying to overcome think-
ing in separate systems and to highlight the interwovenness of cognitive, moti-
vational, and emotional processes.
Descartes and the Mind-Body Debate
Descartes single handedly revolutionized the psychology and philosophy of emo-

tion by insisting on dealing with mental and physiological processes at the same
time. He thus laid the foundation for the mind-body debate about the relation-
ships between mental and bodily phenomena, which continues unabated. Several
current debates in emotion psychology, for example, about the nature of physi-
ological patterning for specific emotional states or about the potential retroaction
of expressive innervation of the muscles on mental states such as feeling, have
generated heated controversy. Much of this is because the relationships between

cognitive events and bodily changes remain uncharted and are often neglected.
It has only been in recent years that theorists have attempted to link the antecedent
evaluation of events (which was described by Aristotle, Descartes, Spinoza,
Hume, and many other philosophers as the determinant of the nature of the en-
suing emotion) to potentially stable patterns of adaptive responses in the central,
peripheral, and somatic nervous systems of organisms (Scherer, 1984a, 1987;
Smith, 1989; Smith & Ellsworth, 1985; Stemmler, 1996).
Darwin and the Biology versus Culture Debate
Of all historical works, Darwin's seminal book The Expression of Emotion in

Man and the Animals (1872/1998) has probably had the most sweeping and en-
during influence on modern psychology of emotion. He is responsible not only
for the strong emphasis on the expression of emotion in face, body, and voice
but also for many of the current concerns of emotion psychologists such as in-
tercultural studies and developmental approaches. Most importantly, his obser-
vation of the widespread universality of a large number of emotional phenom-
ena, particularly expression, has been the basis of a psychobiological current of
theorizing that has long dominated the psychology of emotion (Ekman, 1972,
1973, 1984, 1992a; Izard, 1971, 1991, 1992; Tomkins, 1962, 1963, 1984). This
tradition has been strongly attacked by anthropologists and social psychologists
both early on (Mead, 1975) and, with renewed fervor, recently (Fridlund, 1994;
Russell, 1994). As is often the case, the answer seems to lie in the middle. One
can make a strong argument that emotion elicitation and emotion reaction are af-
fected by both psychobiological and sociocultural factors (Ekman, 1972; 1992;
Ellsworth, 1994; Mesquita, Frijda, & Scherer, 1997; Scherer & Wallbott, 1994).
James and the Center-Periphery Debate
William James's revolutionary suggestion (1884) that the emotion is the per-
ception of differentiated bodily changes, specific for each emotion, has had a
mixed impact on emotion psychology. While it catapulted the study of emotion
to the forefront of the concerns of the young science of psychology at the time,
it also led to a number of enduring confusions and quite sterile cul-de-sacs in re-
search. As mentioned above, if one focuses on feeling as one of the components
of emotion and as a reflection of what is happening in other components or modal-
ities, James's suggestion that emotion is equal to feeling, as determined by the
patterning of expressive and physiological reactions, is certainly acceptable, at
least in part, to many modern psychologists. However, James' use of the term
emotion, thereby referring to the complete process, including antecedent evalu-
ation, while addressing only one component of the reaction, has muddled the is-
sue. James himself became aware of this problem later and added that the bod-
ily changes were determined by the overwhelming "idea" of the significance of
the elements of a situation for the well-being of the organism (James, 1894,
p. 518; see Scherer, 1996, pp. 282, 291-292).
The issue was further complicated by Schachter (1970), who proposed a the-
ory of emotion that has dominated the textbooks for the last 30 years. Because
there was little evidence for James's postulate of highly differentiated response
patterning for specific emotions, Schachter suggested that an increase in general
arousal would be sufficient to render the organism attentive to an emotion being
experienced and to engage the organism in cognitive interpretations of the envi-
ronment to find suitable emotion labels as justification for the increased arousal.
Although this scenario might well happen under certain circumstances, it is highly
improbable that this is the typical pattern for emotional processes. Consequently,
the scenario is hardly a sufficient basis for a theory of emotion. Yet Schachter
and Singer's ingenious experiment (1962), which has yet to be clearly replicated,
plus Schachter's persuasive argumentation have maintained the popularity of this
peripheral theory until quite recently.
These examples show to what extent the "giants" of the past have influenced
theorizing and debate in emotion psychology and still do so today. They also in-
dicate the necessity for current and future theorists to distance themselves from
these early influences and to reevaluate the degree to which conceptualiza-
tions dating back hundreds of years provide a reasonable basis for present-day
theorizing.
CURRENT PSYCHOLOGICAL MODELS OF EMOTION
Although there are several criteria with which to categorize the many current con-
ceptualizations of emotion, the criterion of differentiation seems one of the most
useful. Current emotion theories differ greatly with respect to both the number of
emotions the theory is expected to explain and the principles that are evoked for
the differentiation. In the following discussion, the currently used models are clas-
sified into four categories to highlight the principles that seem common to the re-
spective approaches. Although there is obviously some variance between the mod-
els within each category, it is suggested that between-category variance is quite
a bit larger than the within-category variance. It should be noted that both cate-
gorization and labeling are the result of the author's personal analysis of the bulk
of theoretical work and may not be shared by other theorists.2
2
In this discussion, the terms theory and model are used interchangeably and generously (in the
sense that some of the approaches mentioned might fall short of the requirements for a theory in the
full-fledged sense).
Dimensional Models
Unidimensional models
Proponents of unidimensional models, while acknowledging the existence of
a multitude of fine distinctions between emotional states bearing different names,
are convinced that one dimension is sufficient to make the important analytic
distinctions. Depending on the theorist, this dimension is activation/arousal or
valence, respectively. The idea that the major difference between emotional states
is the relative degree of arousal from very little to very much was quite influen-
tial when general arousal models in physiology were popular. A pertinent ex-
ample is the work of Duffy (1941), who is frequently cited as having advocated
the abolishment of the term emotion in favor of the adoption of a continuum of
terms to denote general excitation. Although such activation or arousal dimen-
sion models (with low versus high excitation poles) are no longer used much,
the fundamental idea still permeates some of the theorizing and research in the
area.
Many early psychologists argued that the pleasantness-unpleasantness dimen-
sion was the most important determinant of emotional feeling. This approach
holds that the most important principle for emotion differentiation is valence,
ranging from a bad, disagreeable, or unpleasant pole to a good, agreeable, or
pleasant pole. This dimension allows one to distinguish between negative and
positive emotions, a distinction that is intuitively appealing because it not only
captures what is generally seen as the most important dimension of feeling but
also reflects the two fundamental behavioral orientations of approach and avoid-
ance (Schneirla, 1959). The distinction between positive and negative affect has
been highly popular in sociopsychological treatments of emotional and affective
states (e.g., Diener & Iran Nejad, 1986; Isen, Niedenthal, & Cantor, 1992) and
it is currently one of the most accepted criteria for studying affect and mood
states in social psychology, particularly social cognition (Clore & Parrot, 1991;
Forgas, 1991; Schwarz, 1990) and personality. In the latter area, the idea of in-
dependent positive and negative dimensions, as in the so-called PANAS model
(positive and negative affect scales) (Watson, Clark, & Tellegen, 1988) is in-
creasingly popular.
Multidimensional models
One of the first suggestions for a multidimensional system was made by Wundt
(1905), who advocated the use of both introspective and experimental methods,
using physiological measurement, to study emotional feeling. He proposed that
the nature of the emotional state was determined by its position on three inde-
pendent dimensions: pleasantness-unpleasantness, rest-activation, and relax-
ation-attention. This three-dimensional model had a strong impact on early emo-
tion psychology. Thus, Schlosberg (1954) propagated a three-dimensional model

in American psychology, and he used two-dimensional models to study facial
expression (Schlosberg, 1952). One of the attractions of this type of modeling is
probably the fact that a multidimensional analysis of meaning transcends the
study of emotion. Thus, Osgood and collaborators (see Osgood, May, & Miron,
1975; Osgood, Suci, & Tannenbaum, 1957) showed that virtually all linguistic
and nonlinguistic concepts can be placed into such a three-dimensional space
(valence, activation, and power) with respect to their meaning structure.
Multidimensional models have been popularized by Plutchik (1960,1982) and
Russell (1980, 1983). Both of these writers have postulated a two-dimensional
scheme, with the standard emotions placed on a circle or circumplex in this space
(valence, activation). Such two-dimensional models are appealing in that they al-
low one to graphically illustrate similarities and differences between emotions in
terms of neighborhood in space.3
Dimensional models have been at the basis of much recent physiological and
neuropsychological emotion research, which often emphasizes the valence di-
mension (e.g., Lang et al., 1993). Davidson (1992, 1993) has suggested a model
that links the phylogenetically continuous approach-avoidance mechanism to
positive-negative valence, postulating specific brain localizations for these func-
tions. Borod (1992, 1993) has comprehensively reviewed the dimensional mod-
els that are currently used in the neuropsychology of emotion. In conclusion, al-
though theorists adhering to dimensional models do not deny further differences
between emotions, they remain fundamentally convinced that the functional dis-
tinction between approach tendencies in positive emotional states and the avoid-
ance tendencies in negative emotional states is the basis of the neurophysiolog-
ical and psychological affect differentiation.
Discrete Emotion Models
Circuit models
Circuit models, committed to a neuropsychological approach to emotion, sug-
gest that the number of fundamental emotions and their differentiation are de-
termined by evolutionarily developed neural circuits. The first such attempts to
demonstrate emotional circuits in the brain were made by Cannon (1927), Papez
(1937), and Arnold (1960). More recently, the two most prominent protagonists
of this tradition have been Gray (1990) and Panksepp (1982, 1989).
3
Evidence for a circumplex arrangement (Russell, 1980, 1983) is difficult to establish unequivo-
cally because the spatial arrangement resulting from proximity analyses depends strongly on the se-
lection of appropriate labels or expressions. Thus, one can demonstrate that by choosing a large ar-
ray of verbal labels, one can fill the complete two-dimensional space with clouds rather than
circumplex donuts (Gehm & Scherer, 1988; Scherer, 1984b).
Panksepp argues for four fundamental circuits, or emotive command "sys-

tems," which are expected to produce well-organized behavioral sequences
elicited by neural stimulation: rage, fear, expectancy, and panic. Each of these
neural circuits has very clear behavioral outputs. It is expected, however, that
various interactions among these systems can lead to "second order emotive
states" consisting of blended activities across the primary systems. This adjust-
ment of a circuit model is obviously necessary once one moves from the emo-
tional behaviors of lower mammals to primates, especially humans. In contrast,
Gray (1990) highlights the biological mechanisms underlying attention and re-
inforcement.
Basic emotion models
Among the most popular conceptualizations of the nature of emotion have been
theories suggesting the existence of basic or fundamental emotions such as anger,
fear, joy, sadness, and disgust. The theorists in this tradition suggest that, during
the course of evolution, a number of major adaptive emotional strategies devel-
oped (this is similar to the claims of circuit models). These strategies are thought
to consist of a limited number, generally between 7 and 14, of basic or funda-
mental emotions each of which has its own specific eliciting conditions and its
own specific physiological, expressive, and behavioral reaction patterns. Thus,
Plutchik (1962, 1980) has proposed a set of basic emotions according to funda-
mental, phylogenetically continuous classes of motivation as identified by etho-
logical research (Scott, 1969).
Many of the discrete emotion models are derived from Darwin's The Expres-
sion of Emotion in Man and the Animals (1872/1998). In this ground-breaking
work, Darwin used a number of major emotion terms in the English language as
chapter headings and demonstrated for each of these their functionality, evolu-
tionary history, the universality across species, ontogenetic stages, and cultures.
The theorist most responsible for the application of Darwin's seminal work to
psychology was Tomkins (1962, 1963, 1984), who extended Darwin's theoriz-
ing to argue that a number of basic or fundamental emotions could be conceived
of as phylogenetically stable neuromotor programs. Although Tomkins did not
describe the nature of these programs in detail, the assumption was that specific
eliciting conditions (which Tomkins sought in different gradients of neural fir-
ing) would automatically trigger a pattern of reactions ranging from peripheral
physiological responses to muscular innervation, particularly in the face (which
Tomkins considered as the primary differentiating effector system).
This concept has been popularized by two scholars strongly influenced by
Tomkins, Ekman and Izard, who extended the theory and attempted to obtain
pertinent empirical evidence, particularly with respect to early ontogenetic onset
of the discrete emotion patterns (Izard, 1994; Izard et al., 1980, 1995), the dis-
crete patterning of prototypical facial expressions for a number of basic emo-
tions, and the universality of these patterns (Ekman 1972, 1973, 1980, 1992b,
1994; Ekman et al., 1987; Izard, 1971,1990, 1994; Levenson et al., 1992). Given
the limited number of such basic or discrete emotions, theorists in this tradition
have had to postulate a mechanism of emotion mixing or blending to explain the
large variety of emotional states that are popularly described by laymen and po-
ets alike. In recent years, both Ekman and Izard have elaborated their theoreti-
cal ideas to account for both the large variety of emotional states (thus Ekman
[1994] talks about "families of emotion") and the effects of the environment and
culture on emotional development (Izard, 1994).
Given that the works of Tomkins, Izard, and Ekman have been responsible for
the renaissance of work on emotion in post-war psychology, which was first dom-
inated by behaviorism and then by cognitivism, much of present-day emotion
psychology is in one way or another strongly influenced by the assumption of
discrete fundamental emotions. Obviously, this idea is strongly supported by the
existence of verbal labels with a very high frequency of usage, such as anger,
fear, sadness, and joy, which serve to describe overarching concepts or proto-
types.
Meaning Oriented Models
Lexical models
The structure of the semantic fields of emotion terms has often been used as
the basis for model building in emotion psychology. The basic assumption is that
the wisdom of the language somehow will help the theoretician to discover the
underlying structure of a psychological phenomenon. Although it is debatable
whether the denotative and connotative structures of the emotion lexicon in a
particular language will neatly map to psychophysiological processes that are
largely unconscious, this type of emotion modeling is intuitively appealing be-
cause it activates common cultural interpretation patterns. One such approach has
been suggested by Oatley and Johnson-Laird (1987), focusing on goal structures.
Ortony, Clore, and Collins (1988) performed a structural analysis of the emotion
lexicon in order to demonstrate the underlying semantic implicational structure.
A different approach was used by Shaver and colleagues (1987), starting from
work on conceptual structure (Rosch et al., 1976), to illustrate different levels of
generality in the classification of emotional states. They used the method of clus-
ter analysis to produce trees of emotion terms with differential degrees of gen-
erality. It is not always clear in the writings of the theorists in this tradition
whether they are mostly interested in understanding the labeling of emotional
states by lay persons, including the accompanying prototypical schemata, or
whether they intend to extend the theoretical modeling to the emotion mecha-
nism as a whole.
Social constructivist models

Another model of emotion claims that the meaning of emotion generally is
constituted or constructed by socioculturally determined behavior and value pat
terns (Averill, 1980; Harre, 1986; Shweder, 1993). Although the proponents of
this approach do not deny the psychobiological reaction components of emotion,
they consider these secondary to the meaning conferred by the sociocultural con-
text with respect to both the interpretation of the eliciting situation and the role
of the emotion reaction in the person's sense-making and social interaction. The-
orists in this tradition are also strongly interested in the emotion lexicon because
they consider that the emotion labels available in a language reflect the emo-
tional meaning structures in the respective culture.
Componential Models
Theorists of componential models start with the assumptions that emotions are
elicited by a cognitive (but not necessarily conscious or controlled) evaluation
of antecedent situations and events and that the patterning of the reactions in the
different response domains (physiology, expression, action tendencies, and feel-
ing) is determined by the outcome of this evaluation process. Although theorists
in this tradition share these fundamental assumptions, their ideas diverge rather
significantly with respect to both the conceptualization of emotion differentia-
tion and the number of major emotions thus predicted.
One of the most restrictive of the componential models is that of Lazarus
(1991). Together with Arnold (1960), Lazarus pioneered the notion of subjective
appraisal, including the significance of an event for an organism and its ability
to cope with the event, on the nature of the ensuing emotion (Lazarus, 1968,
1991). In his most recent modeling, Lazarus postulates a "theme"-based approach,
which argues that a limited number of fundamental themes in appraisal generate
a limited number of major emotions. While more explicitly modeling the elici-
tation process, this idea rejoins some of the fundamental assumptions of the dis-
crete emotion theories, reviewed above.
At the other extreme of the componential models is the component process
model proposed by Scherer (1982, 1984a,b, 1993), which assumes that there are
as many different emotional states as there are differential patterns of appraisal
results. Other theorists in this tradition (e.g., Ellsworth, 1991; Frijda, 1986, 198
Roseman, 1984; Roseman, Wiest, & Swartz, 1994; Smith, 1989; Smith &
Ellsworth, 1985; Smith & Lazarus, 1993) represent intermediate positions. Al-
though these theorists generally do not endorse the idea of a small number of ba-
sic emotions, they tend to agree that there are overarching emotional prototypes
or families. Thus, Scherer (1987, 1994) has suggested the concept of modal emo-
tions, defined as frequently occurring patterns of appraisal or event types that are
universally encountered by organisms, such as sadness in the case of loss or anger

in the case of blocked goals.
One of the major features of componential theories is the effort to render the
link between the elicitation of emotion and the response patterning more explicit.
In many of the other types of models described above, the existence of differ-
ential patterning is either denied, as tends to be the case in dimensional models
(which often still adhere to ideas of general arousal or valence), or ascribed to
fixed neurophysiological circuits or neuromotor programs (as in the discrete emo-
tion models). Theorists in the componential model category have started to work
out detailed predictions of specific physiological, expressive, and motivational
changes as consequences of specific appraisal results (Scherer, 1984a,b, 1986,
1987, 1992; Smith, 1989).
A SYNTHESIS OF THE MODELS
As is often the case in science, none of the classes of theories can be considered
completely erroneous. Because the proponents of these theories are able to muster
theoretical and empirical support for their claims, it is likely that each of the
models captures and explains at least some aspects of reality. When comparing
competing theories, one must determine exactly which of the many aspects of
reality are highlighted by the respective theories and to what extent these aspects
can be mapped onto each other given their relationships in reality. It seems use-
ful to compare models with respect to their major focus. In doing so, it is ap-
propriate to consider the need to rely on verbal labels of emotion to describe the
phenomena to be modeled, something that all emotion models have in common.
The bases of verbal labels of emotional states are the changes in conscious
subjective feeling states. Although the feeling states may reflect all the changes
characterizing an emotion process in all of the organismic subsystems, verbal la-
bels often represent only a salient part of those changes, those that reach aware-
ness (see Kaiser & Scherer, 1997). In many cases, this process of becoming aware
of a change and labeling it may be restricted to individual emotion components.
For example, the term tense, which is frequently used as an affect descriptor,
seems to refer almost exclusively to a special tonic state of the somatic nervous
system, the striated musculature. If a certain set of terms is preferred in one the-
ory of emotion and another set of terms with different referents in terms of com-
ponent coverage is preferred in another theory, it is not surprising to find dis-
agreements between the theories. It can be argued that because of this and related
reasons the different classes of theories mentioned above tend to focus on dif-
ferent components of the emotion process.
Table 6.2 presents the unique profiles of each class of emotion model with re-
spect to its main focus and to the way in which it deals with elicitation and re-
Table 6.2. Differential Foci of Several Psychological Models of Emotion

MAJOR ELICITATION DIFFERENTIATION
MODELS FOCUS MECHANISM MECHANISM
Dimensional Subjective feeling Rarely directly Degree of similarity

addressed; on feeling
rudimentary dimensions such
approach-avoidance as valence and
definition activation
Discrete Motor expression Rarely directly Phylogenetically
emotion or adaptive addressed; continuous
behavior patterns typical situations neuroanatomical
or stimulus circuits or motor
configurations programs
Meaning Verbal descriptions Rarely directly Socially shared,
of subjective addressed; cultural prototypical mental
feelings interpretation representations
patterns
Componential Link between Appraisal Adaptive reactions in
emotion-antecedent mechanism based motor expression;
evaluation and on a universally physiological
differentiated valid set of criteria, responses to
reaction patterns influenced by appraisal results
cultural and and the action
individual tendencies generated
differences by the results
sponse differentiation. It can be reasonably argued that the dimensional theories

are almost exclusively concerned with the subjective feeling component and its
verbal reflection, which, as described above, lends itself to dimensionalization.
The large number of studies in this tradition that employ factor analysis, cluster
analysis, or multidimensional scaling of emotion words underlines this tendency.
The semantically oriented meaning theories, in constrast, are primarily concerned
with studying the lexicon available for verbally labeling emotional states, an ac-
tivity that, as semantic research tends to do generally, yields tree structures or
taxonomy grids. Discrete emotion theories, historically linked to the study of fa-
cial expression, concentrate on the action system and particularly on the motor
expression component. Because facial expression is the most discrete modality
within the reaction component, it is not surprising to find that of discrete emo-
tion models theorists postulate clearly differentiated patterns in the form of ba-
sic emotions.
These theories not only focus on different components of the emotion process
but they also tend to be driven by different theoretical preoccupations. For ex-
ample, while appraisal theorists are generally concerned with the cognitive front
end, even though venturing predictions as to potential behavioral outcomes, cir-

cuit theorists and discrete emotion theorists mostly focus on the back end, the fi-
nal response pattern subserving adaptational responses. The result of this, as one
might expect, has been a remarkable confusion concerning the concept of emo-
tion coupled with many fruitless debates on the nature of the phenomenon. If one
considers emotion as a hypothetical construct referring to a process involving all
of the above-mentioned components, few of the models described in this chap-
ter can claim to explain emotion as a whole. At most, they can be considered
subtheories, their range of validity being limited by the specific component
processes they concentrate on. Because the components of emotion, and the un-
derlying changes of the subsystems, can hardly be considered to be independent
of each other, these partial theories need to be mapped onto each other. If one
takes their respective foci of attention into account, they are actually much more
compatible than is usually assumed.
The componential models, given the large number of facets of emotion that
they encompass, might provide a suitable basis for such an attempt of mapping
models onto each other. The dimensional structure of a "feeling space" as pos-
tulated by dimensional theorists does not contradict the postulate of component
theorists that subjective feeling is one component of the total emotion process.
On the contrary, one can even show ways in which major appraisal dimensions,
such as goal conduciveness, urgency, and coping potential, map directly onto the
feeling dimensions of valence, activation, and power/control (see Scherer, 1984b).
As discussed above, componential models often acknowledge the existence of
overarching emotion families or modal emotions, thus allowing one to bridge the
gap to discrete emotion theories. Although component theories do not share the
idea of a limited number of emotion-specific neuroanatomical circuits, they do
postulate phylogenetically continuous, adaptive reaction patterns and action ten-
dencies as produced by appraisal results.
With respect to meaning theories, component theorists share the social con-
structivists' insistence on the powerful role of sociocultural determinants of emo-
tional experiences by assuming, for example, that cultural values can strongly
affect appraisal, that the regulation of the emotion depends on norms and social
context, and that the subjective experience reflects the sociocultural context.
Component theorists do not, however, go as far as to maintain that emotional
episodes are constituted entirely on the basis of cultural meaning structures. The
findings of lexically oriented meaning theorists can also be easily integrated into
component theories. Because the verbal labels can be expected to denote the con-
scious part of the feeling component (which is seen as reflecting the changes in
all other components, including the cognitive, appraisal component), one would
expect to find the semantic structure of the emotion lexicon to reveal both typi-
cal appraisal configurations and reaction prototypes.
CURRENT FOCI OF PSYCHOLOGICAL EMOTION RESEARCH
The current foci of interest in psychological theorizing and research on emotion

can be grouped into three major categories: (7) the elicitation and differentiation
of emotion through antecedent evaluation, (2) the emotion-specific response pat-
terns of different modalities, and (3) the effects of emotion on other types of psy-
chological functioning such as memory or judgment. These domains are briefly
described here to demonstrate the ways that psychological models of emotion are
put to use in research practice.
Emotion Elicitation and Differentiation
The issue of what determines whether an emotion is elicited and which kind of
emotion will ensue can be approached from two different vantage points, an ex-
ogenous one, involving external events and situation changes outside of the or-
ganism or behaviors of self and others, and an endogenous one, based on the ac-
tivation of memorized schemata or neurohormonal changes within the organism.
The exogenous point of view has been receiving renewed attention since the
pioneering work of Arnold (1960) and Lazarus (1968) on the important role of
the subjective appraisal of an event in emotion differentiation. Since the mid-
1980s, many psychologists have proposed appraisal models of emotion
(Ellsworth, 1991; Frijda, 1986; Oatley & Johnson-Laird, 1987; Roseman, 1984;
Scherer, 1984a,b, 1986; Smith & Ellsworth, 1985), postulating that organisms
evaluate events and situations in a number of given dimensions with the result
of the appraisal process determining the nature of the ensuing emotion. This area
has shown some remarkable convergence among the different appraisal theories
that have received very strong and consistent support in experimental work de-
signed to test the predictions (for a detailed review of this tradition, see Scherer,
1999).
One of the major criticisms leveled against appraisal theory is its presumed
cognitive bias. Critics, however, have offered little with respect to alternative ex-
planations of the elicitation and differentiation of the vast majority of emotional
episodes. Appraisal theorists do not deny that emotions and particularly other af-
fective states (as defined in Table 6.1) can be caused by other mechanisms, for
example, the endogenous factors discussed below. Appraisal theorists have
pointed out (Leventhal & Scherer, 1987; Scherer, 1984a) that the emotion-
antecedent evaluation process can occur in a highly automatic fashion (for a dis-
cussion of the distinction between controlled and automatic processing, see
Shiffrin & Schneider, 1977) and in a largely unconscious way. The idea of
emotion-antecedent appraisal occurring at different levels of the central nervous
system (e.g., the sensorimotor, schematic, or conceptual level) has been proposed
independently by a number of theorists approaching emotion from cognitive, clin-

ical, and physiological perspectives (Mathews, 1988; Ohman, 1988). Several the-
orists are currently attempting to design experiments to more clearly distinguish
the underlying processes and their different levels and relationships (such as top-
down or bottom-up influences; see Van Reekum & Scherer, 1997). Given the
strong link between these traditions and work in the neuropsychology of emo-
tion (e.g., the highly pertinent dual path model of emotion elicitation suggested
by LeDoux [1989]), the study of levels of processing is one of the most prom-
ising meeting points between psychologists and neuroscientists working on
emotion.
The study of the endogenous factors likely to elicit and differentiate emotions
is another such meeting point. The work done by Gray (1990) and Panksepp
(1982, 1989) on neuronal circuits involved in the generation and differentiation
of emotion and the potential effects of hormonal changes or drug intake are im-
portant examples of studies of endogenous factors. Another area of major inter-
est is that of memory models that specify the mediating effects of neuropsy-
chological mechanisms due to pathology (e.g., Damasio, 1994) or memory sub-
systems (Johnson & Multhaup, 1992). Another endogenous factor of interest,
largely unexplored (except for important work on temperament), concerns the
mediating effects of individual differences. For example, it is probable that spe-
cific features of an individual's central nervous system (e.g., cognitive speed or
varying neurohormonal states) can affect the cognitive evaluation of situations
or events (see Van Reekum & Scherer, 1997).
Patterning of Reaction Modalities
Much of the research on the psychology of emotion has been concerned with the
patterns of changes in motor expression, physiology, and subjective feeling (the
reaction triad described above). With respect to physiology and expression, one
of the major goals has been to demonstrate empirically the specificity of pat-
terning. As discussed earlier, many of the psychological models described in this
chapter require at least some degree of specificity. The discrete emotion models
are located at one extreme of the specificity debate, suggesting a rather high de-
gree of neuromotor and neurophysiological patterning. It has generally been the
work of the proponents of these models (such as Ekman, Davidson, Levenson,
and Izard) that has yielded empirical results showing a fairly high degree of
emotion-specific patterning. With respect to expression, the fact that judges are
reliably able to decode patterns of facial and vocal expressions of emotion pro-
duced by trained encoders (Ekman, 1984, 1992b; Scherer, 1989) suggests that
the assumption of specificity of patterning, even though somewhat difficult to
establish for actual facial movements (Gosselin, Kirouac, & Dore, 1995) or
acoustic features (Banse & Scherer, 1996), remains viable. Because similar
judgment approaches cannot be used to examine—even in an indirect fashion—

physiological response patterning, researchers will need to demonstrate consis-
tent configurations of physiological parameters characterizing specific emotional
states. The degree to which the available evidence supports this assumption is
strongly debated (Cacioppo et al., 1993; Levenson, 1992; Stemmler, 1996).
Surprisingly, the domain of subjective feeling states, which is the central re-
sponse component for many emotion theorists, has received relatively little atten-
tion despite the burgeoning interest in consciousness. There have been few attempts
to specify more clearly exactly how subjective feeling states could be conceptual-
ized. Scherer (1987, 1993) has offered the definition of subjective feeling as a re-
flection in the central nervous system of all changes in both the central and pe-
ripheral systems during an emotional episode. This conceptualization does not
require subjective feeling to be conscious. Rather, it can be assumed, as mentioned
above, that only a small portion of the complete set of reflections of all ongoing
changes reach the level of awareness or consciousness. An even smaller set of such
aware reflections can in fact be verbalized (Kaiser & Scherer, 1997).
Traditionally, subjective feeling state has been measured exclusively via ver-
balization with a number of scales such as the Nowlis Mood Checklist or the
Izard Differential Emotion Scale (DES). There has been very little effort to im-
prove on the measurement of this important component of the emotion process
(see Borod et al., Chapter 4, this volume). Some of the newer instruments, such
as the positive-negative affect scales (PANAS; Watson & Tellegen, 1988) are
directed toward valence rather than differentiated emotion states. It remains to
be seen to what extent electroencephalography and neuroimaging methods will
be used as nonverbal measures for subjective feeling (Davidson, 1992, 1993).
One of the major research issues in the domain of emotional reactions has been
the interaction between different components. In particular, the question to what
extent there is proprioceptive feedback from expressive innervation of the mus-
culature about the quality and intensity of feeling states has been intensively stud-
ied (Cappella, 1993; Laird & Bresler, 1992; Leventhal & Tomarken, 1986; Mat-
sumoto, 1987; Tourangeau & Ellsworth, 1979). Although the findings of some
studies reporting feedback effects are hotly debated, the general pattern of the
results suggests that a weak version of the proprioceptive feedback hypothesis
might be viable.
Effects of Emotion on Other Psychological Functions
After a period of almost exclusive interest in emotion-free, cold cognition, there

has been a remarkable surge of interest in hot cognition, that is, the way in which
memory, learning, thinking, and judgment are affected by affective states. There
is now rather consistent evidence showing that emotional states can have rather
powerful effects on cognitive processing of various types, highlighting the need
to focus on the interaction between cognition and emotion rather than trying to
separate the two. The phenomena of particular interest to this new research are
the effects of implicit or unconscious processing (Kihlstrom, 1987; Mathews et
al., 1989; Niedenthal, 1990). Although most of this research has been driven by
the valence-oriented dimensional theories, one might expect interesting findings
from experiments in which other emotion conceptualizations are used to influ-
ence cognitive functioning. The specific effects of anger on cognitive pro-
cessing, for example, are almost part of the popular lore. Clearly, research into
hot cognition is a promising meeting point for emotion psychologists and
neuropsychologists.
CONCLUSIONS
It remains to be seen which types of psychological models and research para-

digms will best predict the responses of an individual to a particular stimulus or
situation. It seems essential that any theoretical model of the response process
will have to account for the nature of the antecedent processing, particularly the
evaluation of events triggering the emotion and the relationships with the re-
sulting pattern of reaction in different modalities. As argued above, it may well
be possible to achieve convergence between the various psychological models
discussed in this chapter after acknowledgment of their different foci and re-
spective explanations for various aspects of the emotion process. The compo-
nential model might serve as a useful basis for such an attempt at convergence
given the breadth of its focus with respect to the components of emotion and its
attempt to theoretically predict the appraisal-reaction link in an explicit, detailed
fashion. A final criterion for a psychological model of emotion is the degree to
which it can be incorporated into the conceptual and empirical structures of ad-
joining disciplines such as neurophysiology, allowing easy transfer of concepts
and findings.
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7
A Social Cognitive Neuroscience
Approach to Emotion and Memory
KEVIN N. OCHSNER AND DANIEL L SCHACTER
In the movie Blade Runner, a woman named Rachel discovers that what she has
always believed to be her most poignant childhood recollections are not her mem-
ories at all. Rachel learns that she is an artificially created, genetically engineered
entity known as a replicant She is physically indistinguishable from ordinary
humans, and her psychological identity is based on memories taken from the life
of her creator's niece. But if the personal past revealed in her recollections is
imaginary, then who is Rachel? How can she think about herself in the present
or plan for the future unless there is a past self to serve as a point of departure?
As one of us put it recently, "Memory's usefulness does not lie in its ability
to replay the details of our lives with total accuracy, but in its power to recreate
and sustain the important emotional experiences of our lives" (Schacter, 1996a).
For Rachel, memories of childhood were certainly not accurate in the conven-
tional sense, but they did provide her with an essential backdrop against which
her present experiences could be evaluated. This backdrop is as essential for us
as it is for replicants because memories, be they real or artificial, are an essen-
tial means of grounding our emotional lives; indeed, the behavior and reactions
of replicants without a personal history was childlike and unpredictable, and they
experienced life not as a coherent flow of comprehensible experience, but as a
series of unexpected actions, consequences, and potential threats. This fictional
example serves to illustrate that recreating emotional experiences is an essential
163
means of making sense of who we were in the past, who we are now, and who
we might become in the future (Ross & Conway, 1986).
In this chapter, we examine how emotion influences memory by exploring the
functional role that the appraisal and encoding of emotional experiences, and sub-
sequent recall of them, plays in everyday life. Rachel's story illustrates the im-
portance of recalling emotional events for defining the self. But certainty of self
is only one functional end that memory of the emotional past makes possible.
Recalling significant events serves current goals and can aid in the regulation of
moods, can motivate current actions, and can be used to predict the consequences
of future ones.
Traditional approaches to the question of how emotion influences memory
have framed the issue in absolute terms, asking whether emotion makes mem-
ory better or worse, whether emotional memories are indelible, whether pleasant
or unpleasant experiences are recalled more readily, or whether emotion pro-
motes memory for central or peripheral detail (e.g., Bradley, 1994; Christianson,
1992; Conway, 1997; Matlin & Stang, 1978). From our perspective, the answer
to each of these questions would include an important qualifier: it depends (see
also Ochsner & Schacter, in press). We include this qualification because, as we
will argue, the exact manner in which emotion influences memory cannot be
specified without reference to how, in a specific situation, memory of one's emo-
tional reactions serves a specific goal.
In this context, emotion is viewed as a process that identifies significant per-
sons, objects, or events (e.g., Frijda, 1986; Lazarus, 1991) and readies appropri-
ate responses to them. Emotions are therefore constructions based on current,
contextually bound evaluations of personal significance and are not enduring
properties of stimuli; the bully I fear today I might embrace tomorrow if I dis-
cover that he is a blood relative. Remembering an emotional experience is also
a constructive process, but one that involves appraisal with respect to past events
rather than current ones, and is similarly shaped by the significance of a given
memory to one's current goals and desires. To say that emotional appraisal or
that remembering is constructive is not to say that the construction process is al-
ways conscious or deliberative; in fact, as we argue below, in both cases con-
struction first involves the operation of quick and automatic processes, with more
deliberative processes coming into play only if need be. Therefore, to understand
the relationship between emotion and memory, we need to understand two kinds
of constructive processes and their interaction: (7) how we determine what is
emotionally significant; (2) how we encode, store, and retrieve information; and
(3) how the former guides the latter. Encoding and retrieval of explicit memory
for specific emotional, and primarily nontraumatic, life episodes are the focus of
this chapter (for an excellent review of the effects of moods on cognition and
judgment, see Bower & Forgas, 1999; for a review of the research and theory
A Social Cognitive Neuroscience Approach to Emotion and Memory 165
concerning memory for especially traumatic events, see Conway, 1997; for a re-
view of emotion and implicit memory, see Tobias, Kihlstrom & Schacter, 1992).
APPROACH AND ORGANIZATION
The goal-oriented approach to understanding emotion and memory that we elab-

orate here draws on and integrates data from social cognition and cognitive neu-
roscience; we call it the social cognitive neuroscience approach. This approach
is distinct from traditional cognitive neuroscience in that it attempts not just to
elucidate abstract information processing mechanisms and their neural substrates
(Ochsner & Kosslyn, 1999) but also aims to understand how these mechanisms
function in the context of current goals and motivations. Cognitive psychology
and neuroscience have impressively demonstrated that memory is an active
process that involves interpretation and construction at all stages (e.g., Schacter,
Norman, & Koutstaal, 1998); social psychology has shown that the memory dis-
tortions or biases produced by the constructive process are motivated and may
be systematically guided by self-relevant goals (e.g., Ross, 1989; Ross & Con-
way, 1986; Singer & Salovey, 1996). In this chapter, we consider how data from
social cognition and cognitive neuroscience together can provide a more com-
plete account of how emotion determines the directions and paths that the con-
struction process takes than could either approach taken alone.
This chapter is divided into three main sections. In the first, we discuss how
appraisal of the emotional significance of information directs attention during en-
coding; in the second, we consider how the encoded information may be modi-
fied by subsequent rehearsal and consolidation; and in the third, we outline the
ways in which goals and emotional cues in the retrieval environment help guide
the construction of memories for these experiences.
EMOTION GUIDES ENCODING
Attention to incoming information enhances subsequent recollection of it (e.g.,

Craik et al., 1996), and attention is drawn to the information appraised as most
significant to one's self in the context of current goals (Lazarus, 1991). These
goals can be simple and global, such as the general goal to avoid physical or
emotional harm, or they can be more specific, such as the desire to attain a par-
ticular promotion, make a good impression, or calm a frustrated friend. Ap-
praising the significance of stimuli to one's self in the context of such current
goals can evoke different emotions depending on the persons and objects in-
volved and on which goals and needs are currently most important (Frijda, 1986;
Lazarus, 1991). Each emotion thus results from appraisals of different kinds of
self-relevance: At turns, we might be sad if we think about the possible irrevo-
cable loss of a loved one from illness, angry if we attribute responsibility for this
outcome to a doctor's failure to give proper care, or hopeful if we feel that the
medical care might result in a cure (Lazarus, 1991).
Although theorists differ in their specifications of which emotions result from
which types of appraisal, most theories specify that appraisal involves the oper-
ation of fast, automatic, and mainly nonconscious processes, as well as conscious
and more deliberate ones (Frijda, 1986; Lazarus, 1991; Ohman, Flykt, & Lundq-
vist, 1999; Zajonc, 1998). The fast and automatic processes seem adapted to mak-
ing a quick bottom-up evaluation of a stimulus in terms of its valence, indicat-
ing that it is good or bad, to be approached or avoided. The slower and more
deliberate processes involve memory retrieval and reasoning to counteract, aug-
ment, or reshape the more diffuse bottom-up signals. Both steps in the appraisal
process can influence what is encoded and later remembered, and we consider
the contributions of each in turn.
Automatic Capture of Attention by Emotion
If benefits the rabbit to be able to identify the hungry fox as quickly as possible.
Indeed, the more quickly an organism can determine if an event or object should
be approached or avoided, the more likely that organism is to survive (David-
son, 1992). Evolutionary survival pressures have served us well: There is good
evidence that merely looking at a stimulus leads to evaluation of it, and once a
stimulus is identified as emotionally self-relevant, it may be difficult to ignore
(Ohman et al., 1999).
Studies of the automatic evaluation effect indicate that bottom-up perception
of a stimulus may reflexively activate information in memory about its affective
properties, thereby providing the first source of information about how to re-
spond to it (Bargh et al., 1992). In these studies, subjects judge the valence of a
target word that has been preceded by a prime word of similar or different va-
lence. Speeding or facilitation of this judgment for prime-target pairs that have
similar valence appears to occur automatically and has been found across a va-
riety of conditions that vary awareness of the prime-target relation (e.g., Bargh
et al., 1992; Fazio, Sambonmatsu, Powell, & Kardes, 1986).
Emotional information also attracts and holds attention, as revealed by stud-
ies employing the emotional Stroop paradigm. In the standard Stroop task, sub-
jects must attend to the color of a word and ignore its identity; the task is diffi-
cult because the relatively automatic process of reading the word interferes with
the relatively controlled process of naming its color. In the emotional Stroop par-
adigm, it takes longer to name the color of emotional stimuli than it takes to
name the color of neutral stimuli, and this difference is taken to reflect a per-
ceptual bias favoring the automatic encoding of affective information (for re-
view, see Williams, Mathews, & MacLeod, 1996). In a prototypical experiment,
Pratto and John (1991) found that normal subjects took longer to name the col-
ors of positive and negative words than it took them to name the colors of neu-
tral words, suggesting that attention was indeed captured by the emotional sig-
nificance of these stimuli. What is positive or negative may differ from person
to person, however, depending on their current goals and concerns. Consistent
with this suggestion, Riemann and McNally (1995) found interference effects
only for emotionally valenced words that were relevant to topics of current con-
cern to their subjects (as assessed by pre-experimental questionnaires). Impor-
tantly, emotion-specific interference effects may disappear when clinical symp-
toms go into remission (Matthews et al., 1995), suggesting that it is the emotional
salience of words specific to the presence of the disorder—not just greater ex-
perience with these words—that underlies the interference effects.
The ability of emotional, and especially threatening, information to attract and
hold attention may help explain why people tend to recall best information that
is most relevant to extracting the affective significance of a stimulus (often re-
ferred to as central details), causing memory for other kinds of information (of-
ten referred to as peripheral details) to suffer. Thus, for example, Loftus and
Burns (1982) found that subjects who watched a videotape of a staged bank rob-
bery in which the escaping robbers shot a small boy in the face had impaired
memory for the events immediately preceding the attack compared with subjects
who viewed a tape in which the robbers simply ran past the boy. This phenom-
enon is sometimes referred to as "weapon focus" in which witnesses to an ac-
tual or simulated crime tend to recall information about the weapons at the ex-
pense of other details about the setting and (Loftus, Loftus, & Messo, 1987).
It is possible that information central to appraising a stimulus is remembered
more accurately simply because subjects look at it longer. A series of studies by
Christianson et al. (1991) suggest, however, that improved memory for emotional
information can occur even when the amount of viewing time for emotional and
neutral information is equated. In studies with either tachistoscopic presentations
or records of eye movements and fixation duration to equate looking time across
emotional and neutral slides, memory was consistently more accurate for infor-
mation central to the content of a set of emotional images. It seems that more
information per unit time can be extracted about central, emotional details, and
heightened attention to these details may be the mechanism that facilitates this
process.
Guidance of Deliberative, Elaborative Encoding by Emotion
In some situations, the quick and automatic classification of a stimulus as good

or bad may be all that is needed to guide our behavior in the most appropriate
way. But in many instances, we need more information about the events we are
reacting to, including why they have happened. For example, suppose you are
bumped roughly while waiting in line at the supermarket. Your quick appraisal
might be negative, perhaps initiating a rush of anger, but it would be smart to
check this reaction if you realize that the bump was accidental, was not a threat,
and was not intended to cause harm. Drawing inferences about the nature of our
feelings in light of additional inferences about the causes of the events that elicited
them, including the intentions and motivations of others, enables us to have
greater complexity of emotional experience and expression (Lazarus, 1991; Stein,
Wade, & Liwag, 1997).
Although there is debate about exactly which parts of the appraisal process (or
which kinds of appraisals) are conscious and controlled as opposed to noncon-
scious and automatic, it seems clear that making inferences about causality and
intentionality relies on the look-up of information in memory (Lazarus, 1991;
Zajonc, 1998). Depending on the emotion elicited, different emotion-specific
scripts or schemas will be accessed, each of which specifies what kinds of in-
formation are important to identify and evaluate (Lazarus, 1991). This knowl-
edge then can be used effortfully to guide attention to the emotionally relevant
internal (e.g., feelings, goals, and plans) and external (e.g., goal-relevant actors
and events) stimuli specific to a given situation (Lazarus, 1991; Stein, Wade, &
Liwag, 1997). In contrast to early accounts of emotion, which suggested that
arousal results in a global disruption of attentional control (Easterbrook, 1959),
this approach suggests that emotion directs attention in a specific way: Schema-
relevant information will be noted and remembered well, whereas schema-
irrelevant information will not be noted and will be remembered poorly (Levine
& Burgess, 1997; Stein, Wade, & Liwag, 1997).
For most emotional schemas or scripts, the actions of others are more relevant
than their appearance. Thus, people recall actions more often than the appear-
ance of perpetrators of real (Yuille & Cutshall, 1986) or simulated (Clifford &
Scott, 1978) attacks and recall themes better than perceptual detail in films de-
picting either a bank robbery or a boy being hit by a car (Christiansen & Lof-
tus, 1987). Studies that have compared memory for central and peripheral details
generally have found increased memory for central, thematic, and appraisal-
relevant information, including weapons (Burke, Heuer, & Reisberg, 1992; Lof-
tus et al., 1987). It is possible that "weapon focus" may result in part from an
effortful direction of attention.
Although schemas may help guide attention to important information, they
may also limit our ability to draw accurate inferences about the causes of oth-
ers' behavior. One way this can happen is when schema-guided encoding leads
us to fill in missing or unattended information as an emotional event unfolds.
Thus, we may recall feelings, motivations, and reactions that were inferred and
not stated explicitly (Heuer & Reisberg, 1990). The need to fill in information
could be made greater if we attempt to divide our limited attentional resources

between internal sensations and external actors and events. This may explain why
Wahler and Afton (1980) found that highly stressed mothers who were having
problems with their children tended to describe their children's behaviors in gen-
eral, dispositional terms (e.g., malicious or naughty) and did not recall situational
antecedents of the behaviors in question.
Dispositional attributions following from schema-driven emotional appraisals
also can have negative consequences for one's perception of self and recall of
personal experiences. A vivid example is found in people who have suffered from
depression or who have attempted suicide. Depressed persons tend to evaluate
events in terms of their relevance to an abstract negative self-concept, thereby
encoding their personal experiences in an overly general way. As suggested by
Williams and Dritschel (1988), these individuals may focus internally, apprais-
ing the significance of an event in ways that confirm a global, stable, and nega-
tive disposition (e.g., "I have always been a failure") and fail to adequately con-
sider the situational antecedents and aspects of their experiences. By turning
otherwise neutral happenings into events diagnostic of their negative self-view,
they can later retrieve only very general, and mostly negative, accounts of their
lives (Williams, 1996). Repetition of this cycle may be an important contributor
to the etiology and perpetuation of depression (Nolen-Hoeksema, 1991).
A tendency to selectively elaborate emotional information relevant to a dis-
position or self-concept may also explain why most people who usually have
very positive self-views (Taylor, 1989) tend to recall (Denny & Hunt, 1992) or
recognize (Mogg, Mathews, & Weinman, 1987) positive words more accurately
than negative or neutral ones after having been asked to judge their self-
relevance during encoding (for a meta-analysis, see Matt, Vasquez, & Campbell,
1992). Similarly, depressed people tend to recall or recognize depression-
relevant words more often than other word types (e.g., Watkins et al., 1992). An
interesting exception to this self-referential rule is exhibited by patients with gen-
eralized anxiety disorder, who tend to recall anxiety-relevant words either no
more often than, or even less frequently than, other word types (see Mineka &
Nugent, 1995). In contrast to depressed and normal people, who readily encode
information that confirms their pre-existing self-views, it seems that anxious in-
dividuals try to avoid elaboration of self-threatening information (Mineka & Nu-
gent, 1995).
Special Neural Mechanisms for Encoding Emotion
Data from neuropsychology, neuroimaging, and animal learning studies provide

converging support for the idea that separate processes are responsible for the
automatic and deliberative encoding of affective information and suggest further
that each may depend on discrete, but interacting, neural systems (see Ochsner
& Felman-Barrett, in press, for complete discussion; see also Reiman, Lane,
Ahern, Schwartz & Davidson, 1996). Support for the existence of a separate pro-
cessing pathway for the quick affective evaluation of objects and events comes
primarily from studies of conditioned emotional responses and functional neu-
roimaging studies of responses to emotional stimuli. In extensive research with
rats, LeDoux and colleagues have shown that learning to associate a light or a
tone with the fearful anticipation of a shock requires only a direct and fast con-
nection between a sensory organ and the amygdala, and the connection can com-
pletely bypass a longer route that sensory percepts take through the neocortex
(see LeDoux, 1995). Research measuring classic conditioning of galvanic skin
responses in humans has also indicated that the amygdala is necessary for learn-
ing to associate aversive physical states with specific visual stimuli (LaBar,
LeDoux, Spencer, & Phelps, 1995).
In humans, functional neuroimaging studies and studies of patients with brain
damage have shown the amygdala to be linked to the encoding of emotional in-
formation. For example, amygdala lesions will disrupt recognition of the emo-
tions conveyed through facial expression, especially fear (e.g., Adolphs et al.,
1994; Calder et al., 1996; for review of lesion studies, see Borod, 1992), and fear
but not happy faces activate the amygdala, even when presented subliminally
(Whalen et al., 1998). Similarly, amygdala activity measured during presentation
of an emotional story has been found to be highly correlated with greater sub-
sequent recall of the emotional elements of the story (Cahill et al., 1996), whereas
patients with degenerative decay of the amygdala show impairments in their mem-
ory of these elements (Cahill et al., 1995). The selective importance of the amyg-
dala for encoding emotional memories also has been demonstrated by studies of
amnesic patients with an intact amygdala. Such patients can acquire affective
preferences for music (Johnson, Kim, & Risse, 1985), can develop valenced at-
titudes toward people based on their experience with them (Johnson, Kim, &
Risse, 1985), and can acquire conditional fear responses (Bechara et al., 1995)
even though they cannot consciously remember their experiences with these var-
ious sorts of stimuli. Release of the neurotransmitter norepinephrine within the
amygdala appears to be the mechanism by which the amygdala "stamps" in emo-
tional memories, as shown by the memory-impairing effects of drugs that block
norepinephrine in animals and humans alike (Cahill et al., 1994; McGaugh &
Cahill, 1997). LeDoux (1995) has suggested that a neural "significance code" is
quickly computed and stored by the amygdala and may provide a template for
further, more complex stimulus evaluation.
The system responsible for this more complex and deliberative control of af-
fective appraisals seems to involve aspects of the frontal lobe (Damasio, 1994;
Stuss, Eskes, & Foster, 1994). The ability to generate top-down plans, revise or
inhibit habitual responses, and monitor the task relevance of information is im-
paired by lesions of the lateral and dorsal prefrontal cortices (Shimamura, 1995;
Stuss, Eskes, & Foster, 1994). Furthermore, functional neuroimaging studies

show that frontal cortices are activated during effortful, attention-demanding, per-
ceptual or memory tasks that require strategic uses of attention and transforma-
tion of information in working memory (Schacter et al., 1996a; Tulving et al.,
1994; for review of frontal contributions to memory and imagery, see Ochsner
& Kosslyn, 1999). Interestingly, increased activation of the left inferior prefrontal
lobe is associated with amount, or depth, of elaborative semantic processing dur-
ing encoding (Tulving et al., 1994), and this area is hypofunctional in individu-
als with depression (Davidson, 1992; Drevets & Raichle, 1995). This hypofunc-
tionality could play a role in the over-general encoding of experience exhibited
by depressed people (Williams, Mathews, & MacLeod, 1986).
In contrast, the ventral medial frontal (VMF) and orbital frontal (OF) cortices
have unique and strong reciprocal connections with the amygdala and are im-
portant for evaluating the affective, personal significance of choices and using
that information to guide reasoning and action (Damasio, 1994). VMF and OF
lesions may produce deficits in motivation, can result in poor control of affec-
tive impulses, and have been shown to eliminate the anticipatory, "anxious" au-
tonomic response that precedes personally important decisions, thereby render-
ing patients unable to use their feelings to guide actions (Bechara et al., 1996;
Damasio, 1994; Damasio, Tranel, & Damasio, 1990). The mechanism by which
the ventral and medial frontal areas influence the amygdala may involve inhibi-
tion of the stimulus-visceral response associations that the amygdala codes. In
both animals and humans, lesions to these areas may impair inhibition of condi-
tioned responses that are no longer appropriate and limit the recoding of stimu-
lus significance when it has changed (LeDoux, 1995; Rolls, 1995). Furthermore,
using functional magnetic resonance imaging, Davidson and colleagues (David-
son, personal communication) have recently shown that an area of the left me-
dial frontal lobe may tonically inhibit activity in the amygdala and that dys-
function of this connection may be a marker for depression. There have been few
studies in humans that have examined VMF and OF contributions to memory for
emotional information.
Summary
The preceding analysis suggests that emotion is a product of the process by which
we appraise the significance of stimuli and that the interaction of at least two
types of appraisal processes can explain the results of many studies of memory
for emotional events. Quick, automatic processes evaluate the valence of stim-
uli and maintain attention on them, while more deliberate, reflective processes
modify, amplify, or inhibit this initial response, depending on how the signifi-
cance of the given stimulus is appraised relative to current goals and needs. Each
process may involve the action of distinct, but highly interactive neural systems:
The amygdala helps to evaluate stimulus significance quickly, and the prefrontal
cortex can modify an initial appraisal and generate new ones if necessary.
POSTEVENT ELABORATION AND CONSOLIDATION

OF EMOTIONAL INFORMATION
Role of Rehearsal
Every time we ask ourselves about the appearance of the attacker who stole our
wallet, or wonder how our last court case ended in a disappointing loss, we are
rehearsing and re-encoding our memories of those events. Emotional events by
their very nature are significant and self-defining, with our major successes and
failures denoting milestones in our personal development (Ross & Conway, 1986;
Singer & Salovey, 1996). Except for very traumatic experiences (e.g., Chris-
tianson & Nilsson, 1984), in many cases our emotional memories are more of-
ten thought about and recounted to others than are their pallid, nonemotional
cousins (Schacter, 1996b). Public events of personal emotional consequence, such
as the assassination of President Kennedy or the explosion of the space shuttle
Challenger, afford additional opportunities for recoding and rehearsal through
further selective exposure to the event through media, friends, and relatives
(Neisser & Harsch, 1992; Schacter, 1996b).
Negative events are especially likely to be rehearsed, as one repeatedly at-
tempts to understand their significance and why they occurred (Skowronski &
Carlston, 1989); as discussed earlier, if this process becomes habitual and self-
critical, such reappraisals can fuel a ruminative cycle of negative-self evaluation
that may foster depression (Nolen-Hoeksema, 1991). Unfortunately, however, it
may be difficult to avoid rehearsal of negative events, even when one wants not
to do so, because emotional memories may be difficult to ignore or suppress
(Wentzlaff, 1993).
Not surprisingly, therefore, the amount of rehearsal an emotional event re-
ceives generally has been found to influence subsequent memory for it. Thomas
and Diener (1990) asked subjects to record daily experiences in diaries and found
that subjects had a tendency to rehearse and remember more negative than pos-
itive events. Interestingly, we might later overestimate the frequency with which
we experienced negative events, perhaps mistaking frequency of rehearsal for
frequency of occurrence (Singer & Salovey, 1996; Thomas & Diener, 1990).
Broadly consistent results have been obtained by other researchers in studies
showing a modestly positive relationship between affect, rehearsal, and memory
in both old subjects (Cohen, Conway, & Maylor, 1994) and young subjects
(Cohen, Conway, & Maylor, 1994; Conway & Bekerian, 1988; Rubin & Kozin,
1984; see, however, Christianson & Loftus, 1990; Pillemer, 1984). Repeatedly
thinking about an unpleasant experience may enhance memory for it by increasing

the depth with which it is processed (Wagenaar, 1994).
Reminiscence Effects
When tested immediately after encoding, memory for arousing stimuli may be
worse than memory for neutral stimuli, although if memory is tested again hours
or days later, recall of the emotional material may have a distinct advantage (for
review, see Revelle & Loftus, 1992). This rebound in memory for emotional ma-
terial as a function of retention interval is known as a reminiscence effect, and,
although at first it appeared to be reliably demonstrable using both words (Klein-
smith & Kaplan, 1963) and pictures (Kaplan & Kaplan, 1969), some later fail-
ures to replicate under conditions that used slightly different stimuli and proce-
dures cast doubt on the reliability of the phenomenon (e.g., Corteen, 1969).
Christianson (1992) suggested that the effect is most reliable with paired asso-
ciate learning and might reflect some idiosyncrasies particular to that paradigm.
More recent research has produced similarly conflicting results. On the positive
side, Bradley and Baddeley (1990) found a reminiscence-like effect for associa-
tions generated to positive, negative, or neutral words after a 1 month delay, al-
though this result may be more attributable to forgetting of neutral words than to
enhanced memory for emotional ones. On the negative side, Burke, Heuer, and
Reisberg (1992) found only a very small effect of retention interval in recall of
both central and peripheral details of an emotional slide sequence. Despite these
inconsistencies, however, a recent meta-analysis of many of the older studies con-
cluded that the effect is reliable, if not especially large (Park & Banaji, 1996).
An initial account of the reminiscence effect postulated that arousal leads to
temporary inhibition during memory consolidation (Walker & Tarte, 1963). Ex-
actly why this should be the case was, however, never adequately specified. A
more likely explanation has been suggested by Revelle and Loftus (1992). Ac-
cording to their "tick-rate" hypothesis, emotional arousal increases the rate at
which information is encoded, and more information is encoded per unit time
from an emotional than a neutral event (cf. Christianson et al., 1991). In the short
term, it may be more difficult to find any one specific detail among the many
that have been encoded. The increased rate of processing also promotes the rapid
integration and assimilation of encoded details into pre-existing knowledge struc-
tures. In the long term, this means that emotional experiences will have under-
gone more consolidation per unit time than nonemotional experiences, resulting
in relatively greater recall of them
A recent study by LaBar and Phelps (1998) has shown that the amydala is re-
sponsible for this consolidation effect. Patients with unilateral temporal lobec-
tomies were aroused by emotional pictures, but failed to show an improvement
in memory for them over time.
Summary
The appraised emotional significance of objects, persons, or events influences

how much attention is paid to them and how much one elaborates on their sig-
nificance both when they were first encountered and subsequently as their sig-
nificance is reappraised. Emotion thus influences the nature and distinctiveness
of what is encoded and stored and therefore strongly determines what informa-
tion is potentially available for subsequent recall. In the next section, we con-
sider how emotion guides the retrieval of these memory traces.
EMOTION INFLUENCES/GUIDES RETRIEVAL PROCESSES
Constructing a record of a past experience seems to involve at least two steps

(for a more complete discussion, see Schacter, Norman, & Koutstaal, 1998). First,
stored traces interact with retrieval cues either from the external environment or
from those generated internally, and the product of this interaction provides the
"raw material" for recollection (Norman & Schacter, 1996; Schacter, Norman,
& Koutstaal, 1998; Tulving, 1983). Second, decision and reasoning processes
operate on this raw material to help refine, reconsider, and supplement what has
been "served up" in response to the initial retrieval query, and, if further infor-
mation is required, the search can begin all over again by constructing new cues
to retrieve additional specific past episodes (e.g., Schacter, Norman, & Koutstaal,
1998). Appraisal of one's current emotional state, the significance of cues in the
current retrieval environment, and their relationship to goals and the self may
strongly influence the operation of both of these processes.
Affective Retrieval Cues Can Bias Retrieval
The synergistic combination of cue and trace information has been called the
ecphoric process (Schacter, 1982; Semon, 1909/1923; Tulving, 1983), and the
output of the ecphoric interaction is substantially determined by the nature of the
retrieval cue itself. An incomplete, poorly specified, or incorrectly specified cue
may retrieve a memory that is related to, but not an exact match for, the episode
that was desired (Schacter, Norman, & Koustaal, 1998). In the absence of crite-
ria that clearly identify that such close matches are incorrect, these false memo-
ries may be experienced as accurate (e.g., Roediger & McDermott, 1995; Schac-
ter, Israel, & Racine, 1999; Schacter et al., 1996b). This seamless blending of
present and past experience may be a powerful route by which emotion can bias
retrospection.
Sometimes the cues that bias the retrieval process are one's own current af-
fective reactions. For example, Eich et al. (1985) found that individuals currently
experiencing high levels of headache pain tended to recall the pain they experi-
enced in the past as having been more severe than it actually was. For these pa-
tients, present pain cues may have combined with traces of past painful experi-
ences, thereby systematically shifting estimates of past pain to be more like the
level of the pain currently being felt. Although other studies on memory for pain
(e.g., Linton & Mellin, 1982) and memory for mood (Matt, Vasquez, & Camp-
bell, 1992) are compatible with this view, the exact way in which ecphory may
lead to a recall bias in these studies is difficult to assess. Painful experiences and
diffuse moods may have many components, both positive and negative, and it is
difficult to specify exactly which aspects will synergistically combine with ex-
actly what stored information. Furthermore, recall could be influenced by cur-
rent pain levels not because the ecphoric process has been biased but because
current pain and affect primes memories for past experiences with similar levels
of pain or affect, making them more easily accessible (Bower & Forgas, 1999;
Salovey & Smith, 1997).
The power of ecphoric processes to bias recall of affective information was
examined by Ochsner, Schacter, and Edwards (1997) using a procedure that es-
capes the above-noted problems of studying memory for pain and mood. Sub-
jects studied photographs of faces while listening to a corresponding voice speak-
ing in a happy and excited or angry and frustrated tone. When subjects later were
presented with photos of the same people as cues in a recall test for tone of voice,
they tended to recall the pictured person as having spoken in a tone of voice con-
sistent with the affect conveyed by the retrieval cue in front of them: If the face
had a slightly positive expression, they tended to recall that the person had spo-
ken happily; if the face had a slightly negative expression, they recalled the per-
son as having spoken angrily. This recall bias was quite robust, did not depend
on overall level of recall accuracy, and was accompanied by high confidence that
recall was correct. In these experiments, the ecphoric process seems to have been
dominated by the affect present in the retrieval cue rather than the affect present
in the memory trace, and this effect may be related to the dominance of visual
over auditory cues in the perception of nonverbal affective information (Rosen-
thai et al., 1979). This method of controlling the exact nature and valence of cue
and trace information may allow further examination of the specific ways in
which ecphoric processes can bias memory for emotional experiences.
Evaluations of and Judgments About Past Episodes

Are Guided by Current Emotion
If the ecphoric process may occasionally produce information that is systemati-

cally biased by retrieval cues, the second step of the memory construction process
may be subject to even greater influence by emotion. Current goals may set the
occasion for remembering emotional experiences by guiding people to recall
episodes that enhance or preserve a self-concept or help regulate moods and may
even help fill in memories for affective feelings that were not well encoded in
the first place. Furthermore, the emotional nature of what is recalled may also
influence judgments people make about various attributes of their memories.
Retrieval as self-regulation
The constructive recall of affective events may at times be led by the desire
to remember the emotional past in a way that helps create a particular view of
the self in the present (Conway & Ross, 1984; Ross, 1989). For most people,
this view is quite rosy, which suggests that, by and large, people are good at us-
ing recall of past experiences to bolster positive self-regard (Taylor, 1989). This
does not mean that everyone will have a generalized bias to recall more positive
than negative experiences (although this may be the case for happy people; see
Seidlitz & Diener, 1993), but it does suggest that if it is costly or inconsistent
with a current schematic self-view to recall a past mistake or negative experi-
ence, we may distort memory of it in the present. Indeed, examples of this phe-
nomenon abound: Good students tend to recall poor grades as having been bet-
ter than they were (Bahrick, Hall, & Berger, 1996), gamblers tend to recall
unsuccessful wagers as exceptions rather than the rule (Gilovich, 1983), and mar-
ried men whose emotions toward their wives sour over time may recall feeling
less positive about early marital interactions than they initially reported (Holm-
berg & Holmes, 1994, cited by Levine, 1997).
How we remember positive and negative events will be determined by differ-
ences in the individual nature of the self-concept that we are chronically trying
to regulate. Thus, Higgins and Tykocinski (1992) found that individuals who are
motivated by the attainment of positive experiences will better recall informa-
tion related to the presence or absence of positive outcomes (e.g., finding a $20
bill or going to see an eagerly anticipated film that turns out to no longer be play-
ing), whereas individuals motivated to avoid negative experience will better re-
call information related to the presence or absence of negative outcomes (e.g.,
being stuck in the subway or getting a break from a hectic work schedule). An
important aspect of these data is that recall was driven by the focus of the sub-
jects on positive or negative outcomes as defined relative to their enduring self-
goals—and not by the absolute valence of the events. Thus an individual moti-
vated toward achieving positive experiences might remember more about the
failure to achieve a good grade on a test than she will remember about the fact
that her parents did not scold her afterwards, even though the former experience
was aversive and the latter unexpectedly positive (cf. Singer, 1990).
The ability to re-evaluate past experience as congruent with one's self concept
may have important implications for mental health. Indeed, the tendency to give
even stressful life events a positive spin may lead to happiness (Seidlitz & Di-
ener, 1993), whereas a bias to initially interpret situations as confirmations of a
negative self-concept may lead to depression (Nolen-Hoeksema, 1991). The grad-

ual accumulation of positive life experiences, guided by self-enhancing inter-
pretation of events, may be one of the most significant contributors to a stable
sense of subjective well-being (Seidlitz & Diener, 1993; Taylor, 1989).
Retrieval as mood regulation
A powerful way to build and maintain a positive self-concept is to develop the

ability to regulate one's current emotional state. Recall of past personal experi-
ences often occurs in the service of this goal (Erber, 1996). Quite often, this goal
manifests itself in the desire to transform negative feeling states into positive
ones, as shown in 1994 by Josephson, Singer, and Salovey (cited by Singer
Salovey, 1996), who found that induction of a sad mood can lead to conscious
attempts to boost mood through the recall of positive personal experiences (cf.
McFarland & Buehler, 1997). Positive moods may not always be desirable, how-
ever, and Parrott and Sabini (1990) have suggested that people sometimes use
memory to deflate positive moods in order to motivate themselves to work rather
than play, maintain a realistic self-concept, or temper undue optimism. The abil-
ity to regulate mood using memory may be related to one's self-concept: When
in a bad mood, individuals high in self-esteem are more likely than individuals
low in self-esteem to recall positive memories and, in so doing, feel better (Smith
& Petty, 1995).
Importantly, whether or not retrieval of a particular positive or negative mem-
ory has a mood-depressing or mood-elevating effect may depend in large part on
the perspective one takes when evaluating its personal significance during recall.
On the one hand, it is true that replaying an unpleasant experience in one's mind
can depress mood and may prime retrieval of further negative memories (Bower
& Forgas, 1999; Smith & Petty, 1995; Strack, Schwarz, & Gschneidinger, 1985
For example, recall of recent events can boost mood if the events were positive
and depress mood if they were negative (Strack, Schwarz, & Gschneidinger,
1985), and this effect may be increased if one believes that the recalled events
are indicative of one's current abilities to cope with stresses and seek out en-
joyable experiences (Janoff-Bulman, 1992).
On the other hand, recall of a negative event can actually enhance mood if
one's life can be judged as having improved subsequently (Strack, Schwarz, &
Gschneidinger, 1985). This process can be seen particularly clearly in studies of
recall of past painful or traumatic experiences. To feel that one has control over
pain, especially if it is chronic and enduring, it may be important to believe that
one's level of pain has changed over time (Salovey & Smith, 1997). Toward this
end, we may recall past pain as having been more or less intense than it actually
was, depending on which pain level is most adaptive and is most likely to fos-
ter a sense of well-being, control, and hope in the present. Thus, people with high
but not low levels of dental anxiety will recall a trip to the dentist as having been
more painful than it actually was (Kent, 1985), and mothers tend to rate labor
pain as having been less intense 2 weeks after birth than they did during deliv-
ery (Norvell, Gaston-Johansson, & Fridh, 1987). Importantly, current levels of
pain may bias memory for past pain only if current pain influences one's emo-
tional state (Eich, Rachman, & Lopatka, 1990). This suggests that, if current pain
is not aversive enough to affect mood, it will not lead people to recall their past
pain inaccurately.
Whether we view an important, self-defining event as a success or failure can
determine whether it makes us happy or sad (Moffitt & Singer, 1994; Strack,
Schwarz, & Gschneidinger, 1985). In general, reinterpretation of the past can
promote coping and emotional change and may improve mood by allowing peo-
ple to feel that they have learned, grown, and gained control over the factors that
influence their happiness (Folkman & Lazarus, 1984; Janoff-Bulman, 1992). Our
construals of the past are not, however, infinitely malleable: If an experience has
positive or negative effects that are too far-reaching, it may serve as a weighty
anchor that constrains the way we evaluate subsequent life events. In such situ-
ations, a sense of control may be hard to come by. For example, Brickman,
Coates, and Janoff-Bulman (1978) found that lottery winners took less pleasure
than controls in mundane everyday activities, presumably because the extremely
positive experience of winning the lottery had changed the scale against which
they measured the quality of their present experience. Accident victims who had
been rendered paraplegic showed a similar effect, though not because they had
actually experienced a greatly positive event in the past but because they ideal-
ized the past relative to their current state. Paraplegics thus took less pleasure
than controls in daily activities, but did so because they were comparing the pre-
sent to a past that was made more positive in retrospect than it actually was.
Nevertheless, with some limits, recall and causal thinking about even very trau-
matic experiences can benefit mental and physical health. Pennebaker and col-
leagues have shown that systematic writing or talking about traumatic personal
experiences such as the death of a loved one, or instances of physical or sexual
abuse, may boost immune system functioning, reduce anxiety, and improve
grades and work performance (for a brief summary, see Pennebaker, 1997). Im-
portantly, a significant predictor of these effects appears to be how often the nar-
ratives of traumatic episodes include reference to their causes and eliciting cir-
cumstances (Pennebaker, 1997).
These studies illustrate an important point about the way in which we recall
emotional events: Our initial interpretation of a given event's emotional signifi-
cance need not be the last one we ever have, and how we encoded it initially
need not determine how we react to it at recall. Re-evaluation of the significance
of an event in the context of one's current circumstances, with the goal of un-
earthing the factors that lead us to experience maladaptive emotions, can be a
powerful tool for building a happy life (Janoff-Bulman, 1992; Seidlitz & Diener,
1993).
Current appraisals may bias the content of emotional memories

A particularly compelling illustration of the power of current appraisals to al-
ter memory of past appraisals was recently reported by Levine (1997), who stud-
ied the attitudes of supporters of candidate Ross Perot during the 1992 presi-
dential campaign. She first assessed their emotions of hope, anger, and sadness
following from Perot's withdrawal from the race in mid-July. Perot re-entered
the race in early October, and after the election in November, Levine again as-
sessed current feelings about Perot's candidacy and asked the supporters to re-
call how they had initially felt about Perot's withdrawal a few months before.
Although memory for these past feelings generally was fairly accurate, it was
systematically biased to be consistent with current feelings about the desirabil-
ity and implications of a Perot presidency. The key finding was that specific past
emotions were recalled accurately or were overestimated when they were con-
sistent with current appraisals, but were underestimated when they were incon-
sistent with them (cf. Conway & Ross, 1984).
Such systematic distortions in memory for emotions may also occur because
people have theories about how memory for emotions or attitudes change over
time (Ross, 1989). Depending on the emotion involved, these theories might dic-
tate whether feelings increase, decrease, or stay the same across time. Although
they may be transmitted through personal and cultural experience, we may be
unaware that implicit theories are guiding the assumptions we make about the
accuracy of our memories. For example, although research provides only equiv-
ocal support for an increase in anxiety and distress during menstruation, there is
a widely held cultural belief that such distress is prevalent and powerful (Mc-
Farland, Ross, & DeCourville, 1989). McFarland, Ross, and DeCourville (1989)
suggest that adherence to this belief may guide women to recall past menstrual
cycles as having been more aversive than they actually were.
Current appraisals can fill in missing information

In our efforts to remember the emotional past in a way that helps make adap-
tive sense in the present, current emotional concerns can sometimes find their
way into memories of our past feelings simply because these past feelings were
not well encoded in the first place. Consider, for example, Levine's study (1997)
of Perot supporters. In that study, recall of past feelings could have been used
by Perot supporters to justify their current beliefs, as when a "loyal" supporter
who wanted Perot to win in November recalls that he was always hopeful that
Perot would re-enter the campaign. It is also possible, however, that the sup-
porters' initial emotional reactions were not well encoded and that current ap-
praisals helped to "fill in the gaps" in their spotty memories. Thus, when Perot
withdrew, the feelings experienced by a loyal supporter may not have been
strongly encoded, and thus their postelection feelings in November served as a
template for fleshing out their incompletely stored feelings from the past.
Researchers on pain and the affect associated with body states have also sug-
gested that affective reactions may not be stored well in memory: When trying
to recall them, we have no recourse other than to use our current feelings as a
starting point and to use theories about how our feelings may have changed to
revise our initial estimate accordingly (Ross & Buehler, 1993; Salovey & Smith,
1997).
Duration is another dimension of emotional experience that may be poorly en-
coded. Consequently, overall duration of an event may not influence our retro-
spective evaluations of the pleasantness of an experience. Frederickson and Kah-
neman (1993) found that retrospective liking judgments for films were determined
entirely by their positive and negative content and not at all by how long they
lasted. If duration is not well encoded, when asked to explicitly recall the dura-
tion of an emotional episode, we may use memory of its intensity as a guide.
Loftus et al. (1987) found that, as the violent content of film clips increased, so
did subjects' retrospective evaluations of their durations.
We may fail to encode the duration of emotional episodes in part because the
peaks and valleys of pain and pleasure capture and hold our attention so that a
given experience is encoded in terms of its most salient or most recent emotional
aspect. Noting changes in the emotional qualities of a situation could have great
survival value: Knowing when guilt slips into shame, frustration into anger, or
sadness into depression can help us to predict and better understand our own and
others' emotional reactions in the future. In keeping with this idea, Varey and
Kahneman (1992) found that memory for extended emotional experiences was
determined by the rise or fall of pleasant and unpleasant sensation and not by
how long each kind of feeling lasted. In further research, they found that this
bias may even lead people to prefer painful stimulation that lasts for a longer
amount of time as long as it tapers off at the end. Kahneman et al. (1993) had
subjects hold their hand in an unpleasant cold water bath for 60 seconds in one
trial and in another had them hold their hand in the bath for 60 seconds plus an
additional 30 seconds during which the water temperature slowly rose 1°C. Most
of the subjects preferred to repeat the longer trial even though it produced a
greater amount of total painful stimulation.
Finally, it is worth noting that poor memory for perceptual details that are pe-
ripheral and not relevant to extracting the central emotional theme of an evolv-
ing emotion episode (Frijda, 1986) may be due in part to reconstruction of these
details during retrieval because they were not well encoded initially. Attention
does tend to be inwardly directed during emotional experiences (Lazarus, 1991;
Stein, Wade, & Liwag, 1997), and subjects may infer the nature of perceptual
details on the basis of stored knowledge of similar events or from cues in the en-
vironment.
Emotion influences the subjective experience of remembering

As discussed earlier, emotion tends to shift one's focus inward, toward regu-
lation and interpretation of one's internal state (Stein, Wade, & Liwag, 1997).
Focusing inward on one's emotions may lead to recollection of memories from
a first-person field perspective in which events unfold in one's field of view just
as they did initially. In contrast, a more abstract focus during recall may lead one
to recall an event from an observer perspective in which one watches himself or
herself from a third-person point of view (Robinson & Swanson, 1993).
Which perspective we adopt during recall may importantly determine how we
think about the causes of an event and consequently how we appraise the emo-
tional significance of it in the future. Frank and Gilovich (1989) instructed sub-
jects to recall past conversations from either a third-person, observer perspective
or from a first-person, field perspective. When in the observer mode, subjects
tended to make more dispositional attributions for their own and their conversa-
tion partner's actions. This suggests that a detached, emotionally flat focus dur-
ing recall can foster interpretation of past behaviors in terms of stable disposi-
tions, which could have important implications for individuals with depression.
Flat affect during retrieval could lead depressed persons to recall events from an
observer perspective, which may only foster their tendency to encode and think
about past behaviors in terms of stable, dysfunctional dispositions (Nolen-
Hoeksema, 1991).
Subjective ratings of the vividness of a memory may also be related to the
emotion experienced during its encoding. When asked to recall significant (Con-
way & Bekerian, 1988), exceptionally clear (Rubin & Kozin, 1984), or conse-
quential and traumatic (Christianson & Loftus, 1990) personal memories, the ex-
periences recalled are typically rated as highly vivid and emotional. Only a single
study has examined the relation between vividness and recall of both positive
and negative personal experiences. Reisberg et al. (1988) asked subjects either
to recall and rate memories from positive and negative event cues (e.g., "pass-
ing a major examination in school") or to provide narrative descriptions of such
memories in an interview. In both cases, rated vividness of the memories was
highly correlated with the intensity but not the valence of the emotions experi-
enced.
Some problems arise, however, with the interpretation of these different stud-
ies of vividness in autobiographical memory. First, the instructions used to elicit
memories or to guide ratings of vividness may sometimes have biased the re-
sults. For example, Rubin and Kozin (1984) told subjects to recall memories with
a flashbulb-like vivid character (Brown & Kulik, 1977), which may have led
them to rate any clear memory as being more vivid. Second, and more impor-
tantly, it is not clear what memory attributes drive ratings of vividness: Memo-
ries could have been rated as vivid because the subjects were confident in the
memories, because the subjects felt they re-experienced the memories, or because
the subjects thought the memories were intense. Whatever the reason for the re-
lationship, the correlation between emotional intensity and vividness does not
mean the former caused the latter.
A more reliable means for assessing the relationship between recollective ex-
perience and emotion involves what has come to be known as the remember/know
procedure (Gardiner & Java, 1993; Tulving, 1985). In this procedure, when an
item is recognized on a memory test, participants are asked to decide if they "re-
member" that item with attendant sensory, semantic, and/or emotional detail or
if they just "know" that it was seen previously but cannot recollect anything spe-
cific about its prior occurrence. "Remember" responses are sensitive to factors
influencing explicit memory, and, given that judged personal emotional signifi-
cance and self-relevance may boost recall, we would expect that these factors
would make one more likely to "remember" an event as well. Indeed, Conway
and Dewhurst (1995) found that self-referential encoding selectively increases
the prevalence of "remember" recollective experiences. Similarly, Ochsner
(2000) found that highly negative and arousing photographs were more likely to
be "remembered" than were neutral or positive photos (cf. Mogg et al., 1992).
This finding is important because it runs counter to previous failures to find a
difference in memory for positive and negative events (Bradley et al., 1992; Reis-
berg et al., 1988). The previous studies tested only recognition memory, a quan-
titative measure that may not be sensitive to the qualitative effects that emotion
may have on memory.
Neural Mechanisms Involved in Retrieval of Emotional Information
The neural structures involved in retrieving emotional memories include some

that are generally involved in retrieving memories regardless of their emotional
content, plus some of the same structures that are used to encode and evaluate
the initial emotional significance of an experience. The former areas include the
right prefrontal cortex and hippocampus. Both neuropsychological and functional
neuroimaging studies of the recollection of episodic memories have shown that
the right frontal lobe may play an important role in generating effortful retrieval
strategies (e.g., Schacter et al., 1996a,b; Tulving et al., 1994), whereas the hip-
pocampus may help locate stored memory traces and support recollective expe-
rience (Schacter et al., 1996a; for reviews, see Cabeza & Nyberg, 1997; Schac-
ter & Wagner, 1999).
Unfortunately, information concerning neural structures that may be involved
specifically in the retrieval of emotional memories is limited because only a very
few studies have examined emotional memory in neuropsychological popula-
tions, and even fewer have studied emotional memory using functional neu-
roimaging. A few studies have shown that right-hemisphere but not left-
hemisphere lesions selectively impair the expression of emotion (Borod et al.,
1996), as well as decrease the specificity of events reported during autobio-
graphical recall. This is consistent with evidence that the right hemisphere is pref-
erentially involved in the perception and expression of emotional behavior more
generally (Borod, 1992; Borod et al., 1996). Given the consistent finding of right
frontal involvement in retrieval of episodic memories, these data suggest that
there may be some linkage between the mechanisms that govern the retrieval of
episodic memories and the mechanisms that imbue them with emotional flavor.
It is interesting to speculate that one reason the right frontal lobe is specifically
involved in episodic memory is because it may help to re-instantiate the emo-
tional context present during encoding (Cimino, Verfaellie, Bowers, & Heilman,
1991).
A larger body of data come from animal and human studies that support in-
volvement of the amygdala in the encoding of affectively significant information
but demonstrate that the amygdala is necessary for the storage and retrieval of
these associations as well. In studies of fear conditioning, for example, the amyg-
dala appears to be the site where the critical stimulus-visceral response associ-
ation is coded, so if the amygdala is lesioned after training, expression of con-
ditioned fear is prevented (LeDoux, 1995). Studies of rats (Phillips & LeDoux,
1992), monkeys (Zola-Morgan et al., 1991), and human patients with amygdala
or hippocampal lesions have suggested that, although it is the hippocampus and
not the amygdala that is critical for storing the perceptual or conceptual aspects
of an event, the coding of visceral reactions by the amygdala gives a boost to
memory for emotional information (Bechara et al., 1995; Cahill et al., 1994,1995;
Hamann, Cahill, & Squire, 1997; Johnson, Kim, & Risse, 1985).
A handful of neuorimaging studies involving recall of emotional events have
also revealed the activation of structures involved in the encoding and genera-
tion of one's initial emotional reactions to the recollected events. This may be
due, at least in part, to the fact that these studies have been concerned primarily
with identifying the neural structures that support the generation and experience
of emotion and elicit emotion by asking subjects both to recall specific personal
emotional episodes and to view emotionally evocative pictures. These studies
have consistently revealed activation of medial prefrontal cortex and thalamus
(George et al., 1995; Lane et al., 1997a,b), regardless of the kind of emotion be-
ing recalled. As discussed earlier, these areas are also involved in learning and
modulating the expression of emotional responses (e.g., Damasio, 1994). Some
areas of activation specific to the recall of individual emotions have been ob-
served (e.g., the insula has been associated with sadness; Lane et al., 1997b), but,
given the small number of studies conducted thus far, no consistent patterns have
yet emerged.
Interestingly, although amygdala activation has been observed during percep-

tion of emotionally evocative stimuli (e.g., Reiman et al, 1997), greater amyg-
dala activity has not been consistently observed when subjects also are asked to
recall personal, emotional episodes. This could be because the emotion-related
physiological responses that the amygdala coordinates occur only when an emo-
tion is being experienced strongly, and subjects' recollections may not have been
sufficiently vivid to elicit additional amygdala activity. Alternatively, current neu-
roimaging methodology may not be sensitive to small changes in amygdala ac-
tivity that could be generated by recall as opposed to perception of emotional
events (cf. Kosslyn & Ochsner, 1994).
Summary
The preceding analysis suggests that retrieving a memory of an emotional expe-

rience can be biased in two ways. First, cues in the retrieval environment can
combine with stored traces to produce a memory that is consciously experienced
as accurate, even though its affective qualities may be more a product of current
than past feelings. Second, effortful search for, and evaluation of, past emotional
experiences may be shaped by current goals to justify, further, or explain cur-
rent self-beliefs or to alter current moods. In some cases, because the emotions
experienced during a given event were not well encoded, current feelings can
serve to fill gaps in memory; the use of implicit theories of how emotions—and
memory of them—change over time may guide this process. Retrieval of emo-
tional memories may involve the same neural structures used to retrieve neutral
ones, but there is as of yet little evidence to support this claim directly. It is clear,
however, that retrieving past emotional experiences does require the action of
the neural systems used to encode and store specifically affective information.
CONCLUSION
This chapter has drawn from research in both social psychology and cognitive
neuroscience to inform an account of the relationship between emotion and mem-
ory that converges on three important principles: (7) Encoding of emotional ex-
periences is guided by both automatic and deliberative appraisal processes that
capture and guide attention to, and promote elaboration of, information that is
judged to be most personally significant in the context of current goals and de-
sires. (2) Retrieval of past emotional experiences is often biased such that mem-
ories of them make sense when evaluated from the perspective of one's current
goals and feelings about them. (3) Separate but interacting neural systems are in-
volved in the quick and automatic, or more effortful and reflective, encoding and
retrieval of these memories.
Hamlet said, "nothing is either good nor bad, but thinking makes it so," and
this review has outlined some ways that people make use of this ability to rein-
terpret their past in order to serve current and future-looking goals. In doing so,
we have not offered specific directives about exactly which types of details, emo-
tions, or events will be remembered most accurately. Instead, we have attempted
to highlight the individualized nature of emotional processes and the importance
of understanding the reasons why an emotional event is recalled in order to un-
derstand the content of subjective reports about the past. As noted at the outset,
this emphasis reflects our contention that research on emotion and memory should
move beyond questions such as whether emotional memories are indelible or
highly fallible or which kinds of emotion make memory better or worse (e.g.,
see Bradley, 1994; Christiansen, 1992; Conway, 1997; Matlin & Stang, 1978).
These questions often are ill-posed, seek absolute answers that cannot be ob-
tained (Tulving, 1985), and overlook the constructive, goal-driven nature of emo-
tional encoding and recollection (Ochsner & Schacter, in press).
In closing, it is important to note that the work reviewed in this chapter
was weighted most heavily toward the social and cognitive end of the social-
cognitive-neuroscience spectrum. This bias stems from the fact that researchers
only now are beginning to explore the neural bases of emotion and memory, and
as future work maps the structures involved in motivated remembering of emo-
tional experiences, the scales should balance out. Our thinking suggests that this
balancing act will be most successful if researchers remember that remembering
begins with a goal in mind and that feelings follow after.
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8
Neurobiology of Emotion at a Systems Level
RALPH ADOLPHS AND ANTONIO R. DAMASIO
Our understanding of emotion has lagged behind our knowledge of most other
domains of cognition, both theoretically and empirically. In large part, this can
be attributed to the fact that emotion was not considered part of cognition until
very recently. In fact, adherents of both behaviorism and cognitivism made it a
point to exclude emotion and motivation from the study of the mind. Ironically,
it was work in computer intelligence that perhaps first pointed to the impossi-
bility of cognition without emotion. The problem is that information processing,
devoid of emotion and motivation, is without any intrinsic value. Given a con-
strained task, or a specific piece of information to process, a system without emo-
tion can be designed to perform the task or to process the information (as mod-
ern "expert systems" do). But how, in the real world, would such a system ever
decide what to do? Attention, memory, and decision-making all require selec-
tivity; the system must be able to distinguish between inputs and outputs that are
important and those that are irrelevant out of the vast multitude of stimuli and
of behaviors available. Emotion provides such guidance and is indispensable for
the adaptive functioning of higher organisms.
In this chapter, we survey the field from the perspective of large-scale neural
systems that provide the underpinnings of cognitive functions. Our goal is to pro-
vide a modern framework for thinking about emotion that is consistent with stud-
ies in animals and humans and that suggests specific testable hypotheses. Given
194
Neurobiology of Emotion at a Systems Level 195
the constraints of this chapter, our emphasis is on the neural systems responsi-
ble for retrieval of knowledge about emotions, and we focus on two neural struc-
tures: amygdala and right somatosensory cortices.
THEORETICAL OVERVIEW
Damasio (1994, 1995) has articulated a systems-level theory of emotion that is

motivated by an understanding at the levels of evolutionary and ecological de-
scription and that proposes specific neuroanatomical hypotheses for experimen-
tal studies. Fundamental to this view is the idea that the subject matter of emo-
tion is a relation between organism and environment, namely, the effect that
interaction between the two has on the organism's survival and well-being. Emo-
tions thus pertain to the value that stimuli and situations have for the organism.
Survival value ultimately translates into the ability to maintain homeostasis, bod-
ily integrity, and adaptive brain state. Such a biologically motivated view is con-
sonant with several other theoretical treatments of emotion (e.g., Frijda, 1986;
Lazarus, 1991; Plutchik, 1980).
Extending ideas first developed by the psychologist William James over a cen-
tury ago, we propose that an emotion comprises a collective change in body and
brain states in response to the evaluation of a particular event or entity (or in re-
sponse to the memory of a particular event or entity) with respect to its impor-
tance for the organism's survival (Damasio, 1994, 1995). These state changes
produce, respectively, somatic changes (including motor behavior, facial ex-
pression, autonomic changes, and endocrine changes) and changes in the pro-
cessing mode of neural systems (changes in the way the brain processes infor-
mation). Emotions additionally pertain to neural representations of body state
changes (which may be the direct result of actual changes in body state or which
may be centrally generated without any actual body state changes). Emotions
would thus engage those neural structures that represent body states and those
structures that link perception of external stimuli to body states. This would en-
compass somatosensory cortices and components of basal ganglia and structures
such as ventral frontal cortex and amygdala, respectively. Aspects of emotion in-
volving changes in global neural processing modes (as are evident, for instance,
during intense emotional arousal or during states such as depression) would in-
volve neuromodulatory structures such as the basal forebrain cholinergic system,
the noradrenergic locus coeruleus, dopaminergic midbrain and brain stem sys-
tems, and the serotonergic raphe nuclei, among others.
The above framework may seem too inclusive. What are we to make of states
such as hunger, thirst, and pain, which are not normally considered emotions? In
our view, there is no principle difference between these states and emotions, ex-
cept that hunger, thirst, and pain are more primitive, play a lesser role in social
communication, and can be found in a larger number of organisms. Our folk psy-
chological concept of emotion may not acknowledge the continuity, at the level
of neural systems, between hunger, thirst, pain, and emotions. This does not,
however, mean that they are not fundamentally similar; it just means that our
concept of emotion has some arbitrary boundaries (see Griffiths [1997] for an
extended treatment of this issue, although we do not endorse his eliminativism).
The topic of emotion subsumes several distinct processes, which can be oper-
ationalized in different ways. Three useful domains in which emotion can be
studied are knowledge about emotion (including recognition, naming, evaluation,
and appraisal), experience of emotion (a domain that we have labeled feelings
(Damasio, 1995), and expression of emotion (through language, facial expres-
sion, and other behaviors related to social communication).
While recognition, experience, and expression of emotion are all dissociable,
they are also closely linked (for review, see Borod, 1993a). Several lines of ev-
idence bear this out. Perhaps expectedly, the experience and expression of emo-
tion are highly correlated (Rosenberg & Ekman, 1994), although such correla-
tion will depend on the circumstances under which the emotion is expressed
(Fridlund, 1994). Production of emotional facial expressions (Adelman & Za-
jonc, 1989) and other somatovisceral responses (Cacioppo, Berntson, & Klein,
1992) directly cause changes in emotional experience, brain activity (Ekman &
Davidson, 1993), and autonomic state (Levenson, Ekman, & Friesen, 1990).
Viewing emotional expressions on others' faces causes systematic changes in
one's own facial expression (Dimberg, 1982) and emotional experience (Schnei-
der et al., 1994).
KNOWLEDGE OF EMOTION
When we speak of "happiness" or "fear," we are using a verbal label as short-

hand for a cluster of phenomena (experiences, behaviors, body states, and so
forth), knowledge of which comprises the concept of happiness or fear. When
we attempt to assess recognition of emotions by subjects, the particular tasks we
use may engage the subject in retrieving various of these knowledge components.
The retrieval of conceptual knowledge is perhaps most easily understood with
regard to lexical stimuli, such as words. In such an experiment, a subject would
read or hear a word denoting an emotion, for example, the word anger, and would
then be asked to retrieve knowledge regarding the emotion denoted by the word
anger. One could ask, for instance, if this is a pleasant or an unpleasant emo-
tion, if anger is more similar to disgust than it is to happiness, if anger is arous-
ing or relaxing, and so on. All of these items of knowledge are components of
the normal concept of the emotion of "anger." One could perform the same ex-
periment without using the lexical label and instead show subjects a facial ex-
pression of anger, asking the same questions about it as one might ask about the
label.
THE AMYGDALA
Arguably, the brain structure that has received the most attention with regard to
its role in emotion is the amygdala. The amygdala is a collection of nuclei situ-
ated in the anterior mesial temporal lobe that receive highly processed sensory
information from all modalities (although the amygdala receives direct olfactory
input from the olfactory bulb) and that have extensive, reciprocal connections
with a large number of other brain structures whose function can be modulated
by emotion (for review, see Amaral et al., 1992). Thus, the amygdala has mas-
sive connections, both direct and via the thalamus, with the ventromedial frontal
cortices, known to play a key role in planning and decision-making. The amyg-
dala connects with hippocampus, basal ganglia, and basal forebrain, all structures
that participate in various aspects of memory and attention. Of course, the amyg-
dala also projects to structures, such as the hypothalamus, that are involved in
controlling homeostasis and visceral and neuroendocrine output. Consequently,
the amygdala is situated so as to link information about external stimuli con-
veyed by sensory cortices, on the one hand, with modulation of decision-
making, memory, attention, and somatic, visceral, and endocrine processes, on
the other hand. All the latter processes will be influenced by the emotional sig-
nificance of the external stimulus that is being processed. Thus, our decisions,
our memory, our attention, and our somatic responses depend in part on the emo-
tion associated with, or elicited by, a stimulus or event.
Insights into the function of the amygdala date back to lesion studies in ani-
mals that focused on abnormal behavioral responses to emotional and social stim-
uli (Kling & Brothers, 1992; Weiskrantz, 1956). The most consistent finding from
these studies resembled an agnosia for the emotional and social significance of
stimuli, often resulting in pathological tameness and placidity of the animal, to-
gether with a tendency to approach stimuli that normal animals would avoid. Al-
though some broadly similar results have been reported after lesions of the amyg-
dala in humans (Aggleton, 1992; Davis, 1992b), several cases of bilateral
amygdala damage have been reported without the obvious placidity that is typi-
cally found in animal studies (Markowitsch et al., 1994; Tranel & Hyman, 1990).
We have conjectured that amygdala damage may have less obvious consequences
on social behavior in humans than it does in monkeys or rats because humans
possess special compensatory mechanisms, such as language and much greater
general problem-solving skills (Adolphs et al., 1995). Nonetheless, recent data
have confirmed a critical role for the human amygdala in making social judg-
ments about other people, in particular in judging whether another individual is
trustworthy or should be approached. The findings here have been consonant

with those from animal studies: Humans with bilateral amygdala damage tend to
approach and to trust other people who normal individuals judge to be unap-
proachable and untrustworthy (Adolphs, Tranel, & Damasio, 1998).
Insights into the functions of the human amygdala have come also from stud-
ies in which the amygdala was stimulated electrically. Although such experi-
ments are rare, they have found that experiences or behaviors associated with
fear and anger can be elicited by such stimulation (Gloor et al., 1982; Halgren
et al., 1978). The interpretation that the amygdala plays an important role in the
experience of emotions is not presently warranted, however, because a number
of studies with functional imaging have failed to find activation of the amygdala
during the experience of emotions (e.g., Cahill et al., 1996; Fredrikson et
al., 1995).
The Amygdala's Role in Recognizing Emotional Facial Expressions
Neurophysiological recording of neurons in the amygdala of animals has shown

that neuronal reponses are modulated by the affective significance of sensory
stimuli (Muramoto et al., 1993; Nishijo, Ono, & Nishino, 1988) and can be se-
lective for the sight of faces (Leonard et al., 1985; Nakamura, Mikami, & Ku-
bota, 1992; Rolls, 1992). We have studied a rare human subject (subject SM)
who has selective bilateral damage to the amygdala (Tranel & Hyman, 1990)
performing tasks that involved facial expressions of emotion as stimuli. Detailed
analyses of data from magnetic resonance (MR) scans of SM's brain confirmed
complete bilateral lesion of the amygdala, with some minor damage to the adja-
cent anterior entorhinal cortex; all other structures were undamaged (Fig. 8.1).
These findings were corroborated by functional imaging: A resting 18F-
deoxyglucose positron emission tomography (PET) study showed essentially no
glucose uptake by the tissue of the amygdala. When shown facial expressions of
fear, SM often mislabeled the emotion (usually as anger, surprise, or disgust) and
on several occasions was unable to generate any label to describe facial expres-
sions of fear (stating that she had no idea what the face was expressing) (Fig.
8.2). The impairment was verified with a quantitative task in which the subject
was asked to rate the intensity of different emotions signaled by facial expres-
sions. SM gave facial expressions of fear abnormally low ratings of the intensity
of fear expressed, and she also endorsed somewhat low ratings when judging fa-
cial expressions that are similar to fear, such as anger and surprise (Adolphs et
al., 1994, 1995) (Fig. 8.3).
In addition, SM was unable to judge normally the similarity between differ-
ent emotional facial expressions. Whereas normal subjects recognize a contin-
uum of emotions, SM tended to lump all expressions of the same emotion to-
Figure 8.1. High-resolution MR images of the brain of patient SM, who has complete
and selective bilateral amygdala damage. There is minor damage to the anterior entorhi-
nal cortex. All other brain structures are normal. (Top left): Three-dimensional recon-
struction of SM's brain, showing planes of sections. (A) Horizontal section at the level
of the amygdala. (B) Coronal section at the level of the hippocampus. (C) Coronal sec-
tion at the level of the amygdala. All images were obtained by computing an average from
three separate MR scans of SM's brain, providing superior resolution. (Images provided
by H. Damasio, Human Neuroimaging and Neuroanatomy Laboratory.)
gether (they all received nearly identical ratings on a variety of tasks) and judged
different emotions to be very dissimilar (Adolphs et al., 1994). The above results
could not be accounted for by visuoperceptual impairments because the subject
performed normally on a large number of visuoperceptual tasks, including dis-
crimination among unfamiliar faces (Tranel & Hyman, 1990), ability to recog-
nize people's identity from their faces (Adolphs et al., 1994), and ability to dis-
criminate between subtly different expressions on the same face or between sexes.
The finding that the amygdala is important to process facial expressions of fear
has now been replicated in several other studies with both the lesion method
(Calder et al., 1996; Young et al., 1995, 1996) and functional imaging (Breiter
et al., 1996; Morris et al., 1996).
Figure 8.2. Impaired labeling of facial expressions of fear following amygdala damage.
Seven normal control subjects and SM were shown 39 facial expressions of emotion from
Ekman & Friesen (1976) (six of each of the basic emotions, and three neutral faces) and
asked to provide a label of the emotion spontaneously. SM was impaired in labeling faces
expressing fear (she only labeled a single face of fear correctly in the figure). Subjects'
labels are shown as data points when synonymous with the words in the figure (e.g., when
calling angry faces "mad"); labels that are not clear synonyms (e.g., calling a sad face
"guilty") were omitted from the figure (accounting for the absent data points for some of
the control subjects).
Additional studies with subject SM have revealed that the impairment extends
to the retrieval of conceptual knowledge regarding emotions in tasks that do not
involve facial expressions as stimuli. She was unable to draw facial expressions
of fear from memory (Adolphs et al., 1995), and she was also impaired in re-
trieving some conceptual knowledge of emotions when given lexical stimuli, such
as words or stories denoting emotions (Adolphs, Russell, & Tranel, 1999); again,
the impairment was most striking with regard to fear.
We have attempted to decompose SM's impaired retrieval of knowledge of
some facial expressions of emotion by asking her to judge specific components
of knowledge. In one recent experiment, we found that SM was severely im-
paired in knowing that negatively valenced emotions (notably fear and anger)
were highly arousing, while she was entirely normal in knowing that they were
unpleasant (Adolphs, Russell, & Tranel, 1999) (Fig. 8.4).
It is not obvious how to characterize SM's impaired performance on the above
tasks. Interpretations that clearly cannot be made are to conclude that she has no
fear or that she does not know what fear is. The impairment is more specific and
appears to consist of an inability to access some knowledge regarding the emo-
tion signaled by external sensory stimuli, such as facial expressions. This sug-
Figure 8.3. Impaired recognition of fear in
facial expressions following amygdala
damage. Raw rating scores of facial ex-
pressions of emotion are shown from seven
normal controls (top panel), 16 brain-dam-
aged controls without damage to amygdala
(middle panel), and eight subjects with bi-
lateral amygdala damage (bottom panel).
(From Adolphs et al., 1999.) The emotional
stimuli (36 faces; six each of each of the
six basic emotions indicated) are ordered on
the y-axis according to their perceived sim-
ilarity (stimuli perceived to be similar, e.g.,
happy and surprised faces, are adjacent;
stimuli perceived to be dissimilar, e.g.,
happy and sad faces, are distant; cf.
Adolphs et al., 1995). The six emotion la-
bels on which subjects rated the faces are
displayed on the x-axis. Greyscale brigh-
ness encodes the mean rating given to each
face by a group of subjects, as indicated in
the scale. Thus, a darker line would indi-
cate a lower mean rating than a brighter line
for a given face; and a thin bright line for
a given emotion category would indicate
that few stimuli of that emotion received a
high rating, whereas a thick bright line
would indicate that many or all stimuli
within that emotion category received high
ratings. Because very few mean ratings
were < lor > 4, the graphs were truncated
outside these values. Data from subjects
with bilateral amygdala damage indicate
abnormally low ratings of negative emo-
tions (thinner bright bands across any
horizontal position corresponding to an
expression of a negative emotion). (From
Adolphs et al., 1999; copyright Elsevier
Science Publishers, 1999.)
201
Figure 8.4. Mean ratings of arousal and valence for 39 facial expressions of emotion.
Subjects were asked to explicitly rate the same 39 stimuli used in the studies shown in
Figures 8.2 and 8.3 with respect to the valence (pleasantness) and arousal depicted. Data
were averaged for all faces that express the same emotion (six of each basic emotion;
three neutral). Means and standard deviations are shown for 24 normal controls (white
bars) and for subject SM (three experiments; gray bars). SM's ratings of arousal of neg-
ative emotions were more than 2 SD below the control mean (*). (Data are from Adolphs,
Russell, & Tranel, 1999. Reproduced from Adolphs, Russell, & Tranel, 1999.)
gests a role for the amygdala not in storage of knowledge about fear, or in the
experience of fear, but rather in linking external sensory stimuli to systems into
which knowledge about fear is acquired during learning and from which such
knowledge can be subsequently retrieved. The amygdala thus connects percepts
of emotional sensory stimuli, on the one hand, with a variety of neural systems
involved in acquisition of, response to, and knowledge about such stimuli, on the
other. Taken together, the above data support the idea that the amygdala is im-
portant in order to link perception of stimuli that signal potential threat/danger
with behaviors, or with knowledge, related to emotional arousal.
This interpretation makes some specific predictions. First, amygdala damage
should impair the ability to acquire associations between emotional sensory stim-
uli and some components of the normal response to such stimuli. Second, the
amygdala's role in the acquisition of knowledge regarding emotion would pre-
dict that damage to the amygdala early in life would result in more severe im-
pairments in such knowledge (because it would not have been acquired normally
during development), whereas damage to the amygdala later in life might result
in less severe impairments. Third, there should be neural structures other than
the amygdala that are important for the retrieval of knowledge about emotions,
if appropriately triggered. All three of these predictions have been recently tested
and found to be supported. We discuss each in turn below.
The Amygdala's Role in Conditioning
The best studied function of the amygdala concerns its role in associative mem-
ory for aversive stimuli. A large number of studies, primarily in rats, have shown
that the amygdala is required for the acquisition and expression of conditioned
behavioral responses to stimuli that have been previously paired with an intrin-
sically aversive event, a paradigm called fear conditioning (Davis, 1992a; Le
Doux, 1996). The role of the amygdala in fear conditioning as demonstrated in
animals is consonant with recent data from humans: Subjects with amygdala le-
sions fail to show conditioned skin-conductance responses to stimuli that have
been paired with an aversive, loud noise (Bechara et al., 1995; LaBar et al., 1995),
and functional imaging studies in normal subjects have shown amygdala activa-
tion to aversively conditioned stimuli (Buechel et al., 1998). These and other
studies have suggested that the amygdala specifically mediates behaviors and re-
sponses correlated with arousal and stress (Davis, 1992b; Kesner, 1992), in-
cluding a key role in the acquisition of information during emotionally arousing
situations or regarding emotionally arousing stimuli (Phelps & Anderson, 1997).
In one study, we tested the ability of a subject with bilateral amygdala damage
(subject SM) to acquire conditioned autonomic responses to stimuli that had been
paired with an aversive startle stimulus. This experiment was very similar to fear
conditioning experiments with animals (Davis, 1992a; Le Doux, 1996). Briefly,
subjects were presented with a startling, aversive loud auditory stimulus, which re-
liably evoked skin-conductance responses both in normal subjects and in SM. This
startle stimulus was paired with slides of a certain color: Blue slides were accom-
panied by the startle stimulus, whereas slides of other colors were not. Normal
subjects soon acquired conditioned autonomic responses: The presentation of a
blue slide alone (without the startle stimulus) now evoked conditioned skin-
conductance changes. We found that these conditioned autonomic responses were
independent of the acquisition of declarative knowledge because amnesic subjects
also acquired conditioned skin-conductance responses, even though they did not
remember which slides had been paired with the startle stimulus. Subject SM, on
the other hand, did not acquire conditioned skin-conductance responses on this task,
even though she was able to remember which slides had been paired with the star-
tle stimulus (Bechara et al., 1995). These studies suggest that in humans, as in an-
imals, the amygdala plays a key role in acquiring conditioned responses to stimuli
that have been paired with aversive emotional stimuli in the past.
It should be noted that the amygdala appears not to be essential for acquiring
all types of nondeclarative knowledge associated with emotion. In an experiment
with an amnesic patient who had complete bilateral amygdala damage, it was
found that the patient could acquire covert behavioral preferences with regard to
other people: He would develop a positive bias toward people who had been kind
to him in the past and a negative bias toward those who had not (Tranel & Dama-
sio, 1993).
The Amygdala's Role in Learning and Development
Although the above studies provide strong support for the idea that the amyg-
dala is important to acquire responses associated with emotionally arousing stim-
uli, the amygdala's role in acquisition of declarative knowledge regarding emo-
tion has remained controversial. Studies with animals suggested that the amygdala
itself does not contribute to declarative memory and that surrounding white mat-
ter and cortex are instead important in this regard. Recent studies in humans,
however, argue that the amygdala does play a role in declarative knowledge, al-
though this role is modulatory rather than essential, parallel with its modulatory
role in emotionally motivated learning in animals (Cahill & McGaugh, 1998).
In a study of two subjects with complete and relatively selective bilateral amyg-
dala damage, we found a specific impairment in long-term declarative memory
for emotional but not for neutral material. While normal subjects remembered
emotional material better than neutral material, subjects with bilateral amygdala
damage remembered emotional material only as well as neutral material (Adolphs
et al., 1997a). These findings are consonant with a PET study that found that
amygdala activation at the time emotional material was encoded into declarative
memory correlated with how well it could be later recalled (Cahill et al., 1996).
Summary
The findings reviewed above would predict that damage to amygdala might cause
the most severe impairments in declarative memory regarding emotions when it
has occurred early in life, blocking the normal acquisition of such knowledge
during development. Furthermore, the evidence points to a specific role in ac-
quisition of knowledge linked to high emotional arousal, consistent with the
amygdala's importance in knowledge regarding fear, a highly arousing emotion.
Consonant with this idea, we found impaired recognition of facial expressions
of fear in a subject who had sustained amygdala damage early in life (Adolphs
et al., 1994) but not in two subjects who sustained amygdala damage as adults
(Hamann et al., 1996). In an additional study, we probed the knowledge of emo-
tional arousal signaled by facial expressions, words, and stories in three subjects
who had sustained complete bilateral amygdala damage early in life and in two
subjects who had sustained such damage as adults. As predicted, we found that
early-onset amygdala damage caused disproportionately severe impairments in
knowledge of the arousal signaled by emotional stimuli (Adolphs et al., 1997b).

Interestingly, knowledge of the valence (pleasantness/unpleasantness) was nor-
mal in all amygdala subjects in this study (see also Adolphs, Russell, & Tranel,
1999).
Although these studies argue for an important role for the amygdala in the ac-
quisition of knowledge about emotion during development, other lesion studies
(Adolphs, Tranel, & Damasio, 1998; Broks et al., 1998), as well as functional imag-
ing studies (Breiter et al., 1996; Morris et al., 1996), suggest that the amygdala
may serve a more general role in processing emotions and is important for recog-
nizing emotional and social information in adults without developmental damage.
THE SOMATOSENSORY CORTICES
Clinical and experimental studies have suggested that the right hemisphere is
preferentially involved in processing emotion in both humans (e.g., Blonder,
Bowers, & Heilman, 1991; Borod, 1993b; Borod et al., 1992; Bowers et al., 1987,
1991; Ross, 1985; Silberman & Weingartner, 1986; Van Strien & Morpurgo,
1992) and nonhuman primates (Hamilton & Vermeire, 1988; Hauser, 1993; Mor-
ris & Hopkins, 1993). Lesions in right temporal and parietal cortices have been
shown to impair emotional experience, arousal (Heller, 1993), and imagery
(Blonder, Bowers, & Heilman, 1991; Bowers et al., 1991) for emotion. It has
been proposed that the right hemisphere contains modules for nonverbal affect
computation (Bowers, Bauer, & Heilman, 1993), which may have evolved to
subserve aspects of social cognition (Borod, 1993b). There is currently some ar-
gument over the extent to which the right hemisphere participates in emotion: Is
it specialized to process all emotions, or is it specialized only for processing emo-
tions of negative valence (Borod, 1992; Davidson, 1992; Silberman & Wein-
gartner, 1986)? It may well be that an answer to this issue will depend on more
precise specification of which components of emotion are under consideration
(Borod, 1993a; Davidson, 1993).
Selective impairments in recognizing facial expressions, with sparing of the
ability to recognize identity, can occur following right temporoparietal lesions
(Bowers et al., 1985). Specific anomia for emotional facial expressions has been
reported following right middle temporal gyrus lesions (Rapcsak, Kaszniak, &
Rubens, 1989). The evidence that the right temporoparietal cortex is important
in processing emotional facial expressions is corroborated by data from PET
imaging (Gur, Skolnick, & Gur, 1994) and neuronal recording (Ojemann, Oje-
mann, & Lettich, 1992) in humans. Additionally, anthropological analyses of the
depiction of faces in art and painting support the idea that the right hemisphere
is specialized to process the emotional and social signals that faces can signal
(Grusser, 1984).
A prediction made by the hypothesis that the human amygdala is critical for
the acquisition of knowledge regarding emotion is that structures other than the
amygdala would play a key role in the storage and retrieval of such knowledge.
In this view, the amygdala's contribution to memory is in some ways analogous
to that of the hippocampal formation: Both structures are important during ac-
quisition and/or consolidation of new information but are not structures where
such knowledge is ultimately stored. The storage and retrieval of knowledge is
presumed to rely on neocortical sectors.
On the basis of our framework regarding emotion and on the basis of the stud-
ies reviewed at the beginning of this section, we hypothesized that somatosen-
sory cortices in the right hemisphere would be important for the retrieval of
knowledge regarding emotions. We tested this hypothesis in a group of 25 sub-
jects with neocortical lesions performing a task of recognition of emotion in fa-
cial expressions. A detailed analysis of the overlaps of lesions in these subjects
revealed that sectors in right parietal cortex, when lesioned, reliably caused im-
pairments in the retrieval of knowledge about emotions depicted in facial ex-
pressions (Adolphs et al., 1996a). A recent study extended these methods to three-
dimensional analysis of the overlaps of lesions that correlated with the most
impaired performances. The analysis showed that lesions encompassing the face
representation of right primary somatosensory cortex, possibly including SII, in-
sula, and anterior supramarginal gyrus, as well as underlying white matter, most
reliably correlated with impaired recognition of emotional facial expressions
(Adolphs et al., 1996b). The results of this study are shown in Figure 8.5.
The question arises as to why the processing of emotion, much like the pro-
cessing of language, should be notably lateralized. One possibility is that both
language and emotion serve an important role in communication, with a premium
on processing speed. In the case of language, this has been clear for some time:
Both the comprehension and production of language require neural processing
with high temporal acuity. In the case of emotion, ecological considerations would
similarly suggest that signals need to be processed rapidly. The consolidation of
all neural components required to process language, or facial expression, in one
hemisphere would enable such rapid processing. Intrahemispheric delay, on the
other hand, would introduce an unacceptable lag. This constraint would be ex-
pected to be all the more acute the larger the brain, and one would expect later-
alization of function to be especially prominent in human brains, where spatial
proximity of processing components will be a major factor in processing speed
(Ringo et al., 1994).
One interpretation of the right hemisphere's demonstrated specialization in
many tasks involving emotion situates the processing of emotion in relation to
the processing of somatic information. This view (Damasio, 1994, 1995) stresses
that emotion involves output to, and input from, the body (including visceral and
Figure 8.5. Right somatosensory sectors
involved in retrieval of knowledge of the
emotion signaled by facial expressions. We
asked 25 subjects with focal right cortical
lesions to rate facial expressions of emo-
tion, and compared their ratings with those
given by 15 normal controls. Data were
mapped onto a normal reference brain, us-
ing a technique called MAP-3. Briefly,
each subject's lesion was mapped onto the
corresponding spatial location in the nor-
mal reference brain, and greyscale was
used to encode the number of lesions from
different subjects that overlapped at a
given volumetric location. Overlaps from
more subjects correspond to a darker shade
of grey, whereas overlaps from only one or
a few subjects correspond to lighter shades
of grey. All computations were done using
the software BRAINVOX (Frank, Dama-
sio, & Grabowski, 1997) on Silicon Graph-
ics workstations. (A) Lesions of all sub-
jects who were normal in rating facial
expressions of emotion. (B) Lesions of all
subjects who were impaired in rating facial
expressions of emotion. (C) Subtraction
image (B-A) showing the difference in the
lesion overlaps between all impaired sub-
jects and all normal subjects. The subtrac-
tion revealed a focal, three-dimensional re-
gion that when damaged, always correlated
with impaired task performance (dark re-
gion centered on somatosensory cortex).
We thus infer that lesions that include
this region result in impairments due to
damage to this specific region. Detailed
anatomical analyses showed that this re-
gion comprised the face representation of
primary somatosensory cortex (SI), some
of SIT, possibly some insula and supra-
marginal gyrus, as well as considerable
white matter, which may serve to connect
visual cortical regions with somatosensory
cortical regions. (Data are from Adolphs et
al., 1996b.)
207
endocrine aspects). There is evidence that the right hemisphere is specialized for
representing the body, as borne out by the finding that right hemisphere lesions,
more often than left, can cause lack of awareness of one's own body state. It is
quite conceivable that emotion and representation of the body co-evolved and
that both are aspects of the same integrative, homeostatic function, which is rel-
atively lateralized to the right hemisphere.
We can apply this framework to the interpretation of the results given in Fig-
ure 8.5: that lesions in the area of face representation in the right somatosensory
cortex impair recognition of emotion in visually presented facial expressions.
Briefly, we believe that subjects asked to perform the task of recognizing facial
expressions of emotion will normally utilize a somatic image of the face. Given
a facial expression to judge, a subject's normal strategy will include the central
generation of a somatosensory image of the face corresponding to the expression
seen. In essence, the subject approaches the task by asking, "how would I feel
if I had this facial expression" (i.e., how would this face feel)? An apparently
critical component of this strategy is the ability to form a mental somatosensory
image that in turn can be used to trigger other knowledge in both image form
and encoded in language that together permit normal responses on the task.
OTHER STRUCTURES
Several other neural structures are involved in knowledge about emotions, al-
though discussion of these structures falls outside the scope of this chapter. There
is considerable evidence that the frontal lobes, particularly their ventral sectors,
are important to recognize emotions. Lesions in these regions impair the recog-
nition of emotions in facial expressions and prosody (Hornak, Rolls, & Wade,
1996), and ventral frontal cortex and amygdala have been shown to operate as
two components of a neural system for processing the reinforcing properties of
stimuli (Gaffan, Murray, & Fabre-Thorpe, 1993). Additional structures impor-
tant to emotion include the cingulate cortices, sectors of the basal ganglia, and
monoaminergic/cholinergic nuclei that we mentioned at the beginning of this
chapter. The interested reader is referred to Damasio (1995) for further discus-
sion of other neural structures.
GOING BEYOND THE BRAIN
In closing, we wish to return to comments we made at the beginning: The sub-

ject matter of emotion pertains fundamentally to the survival value of interac-
tions between organism and environment. The environment, in the case of higher
vertebrates, includes the social environment. Emotions thus involve not only the
survival of the organism in life and death situations, but also social survival
among members of a group. In the case of humans, the social aspect assumes
great importance, and it is impossible to do full justice to the topic of emotion
without thinking about social development, social communication, and culture.
These topics have been explored in detail by social psychologists and anthro-
pologists, but, at this time, very little is known about the neural systems that are
involved in social and cultural aspects of emotion (e.g., next to nothing is known
about the neural underpinnings of so-called social emotions, such as jealousy,
pride, and embarrassment).
One important direction for the future will be to expand our current account
of emotion. We have a working framework of what emotion shares in common
in all animals; the next task will be to elucidate what distinguishes emotion in
humans from emotion in other animals. We consider it probable that regions of
neocortex, especially in prefrontal cortex, will turn out to play a key role in those
aspects of emotion that are uniquely human (Damasio, 1994). Ultimately, how-
ever, emotions, like other domains of the human mind, may be explained not
solely as properties of individuals, but will be seen to arise from relations be-
tween multiple brains and their external environments, embedded in the context
of a particular culture.
ACKNOWLEDGMENTS
This work was supported by a Sloan Research Fellowship and a FIRST award from NIMH to R.A.
and by a program project grant from NINDS and a grant from the Mathers Foundation to A.R.D.
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9
Neuropsychological Theories of Emotion
GUIDO GAINOTTI
HISTORICAL DEVELOPMENT
The expression "neuropsychological theories of emotion" refers to the set of the-

oretical models that have accompanied and oriented clinical and experimental
studies aiming to clarify the relationships between emotions and the brain. Neu-
ropsychological theories of emotion have been largely influenced by two factors,
on the one hand, by more general psychological and neurobiological models, and
on the other hand, by the characteristicts of emotions and of brain structures taken
as models in studies conducted on specific subjects in a given historical period.
As for psychological theories of emotion (analyzed in detail in this volume by
Scherer, Chapter 6), they have always influenced from two complementary points
of view studies aiming to clarify the problem of the representation and organi-
zation of emotions in the human brain. From the first viewpoint, the representa-
tion of emotions is considered as a loosely organized and fuzzily demarcated be-
havioral system. Studies conducted along this line have basically tried to
determine if data obtained by neuropsychological investigations can be better ex-
plained by making reference to the organizing principle of the emotional di-
mensions (arousal level, emotional valence, motoric direction, and so on) or to
that of the discrete emotional categories. The second viewpoint focuses on the
componential nature of emotions, aiming to determine whether the clinical data
214
Neuropsychological Theories of Emotion 215
point to the existence of a "central processor" of emotions or whether instead le-

sions tend to selectively affect one or another of a set of emotional components
(e.g., emotional computation of sensory data, emotional expression, autonomic
response, emotional experience, and so on), showing that they are subserved by
different parts of the brain.
As for the kinds of emotions and brain structures used as models in different
historical periods, the first studies conducted in this area by Goltz (1892), Wood-
worth and Sherrington (1904), Dusser de Barenne (1920), Bazett and Penfield
(1922), and others were directed at rather primitive emotions, such as rage and
fear, and at the contrasting effects on cognitive and emotional functions produced
by a lesion of cortical versus subcortical structures. The underlying model was,
therefore, that of substantial independence between emotional and cognitive func-
tions in the animal brain. Furthermore, the anatomicoclinical observation that in-
voluntary and uncontrollable emotional outbursts can be observed in patients with
multiple lesions of the corticodiencephalic pathways allowed two further con-
clusions: (1) that this model may also apply to humans, and (2) that in both an-
imals and humans, cortical areas control the subcortical structures subserving the
basic emotional mechanisms.
Studies Focused on Subcortical Structures Subserving the

Basic Emotional Mechanisms
In an effort to identify the subcortical structures that are crucially involved in emo-
tional expression, Bard (1928, 1929) proposed that the hypothalamus may play a
critical role in emotions. It must be acknowledged, indeed, that his model was in-
fluenced by experiments showing that electrical stimulation of the hypothalamus
produces a sustained sympathetic arousal (Karplus & Kreidl, 1909, 1927) and by
the fact that the emotion considered by Bard, namely rage, is characterized by a
strong sympathetic arousal. Nevertheless, Bard's model was considered valid for
emotions in general and oriented the attention of investigators toward the arousal
dimension of emotion. The discovery by Moruzzi and Magoun (1949) that the as-
cending reticular activating system plays a crucial role in arousal functions had,
therefore, a profound influence not only on neurobiological models of the mind
in general but also on more specific neuropsychological theories of emotion.
Several authors (e.g., Duffy, 1962; Lindsey, 1951) were, in fact, led to assume
that the structures subserving the arousal mechanisms also subserve the central
and peripheral components of emotions. In contrast, the much more complex and
articulated anatomical model of emotions proposed by Papez (1937) suggested
that different parts of the brain may mediate different components of emotions.
To be sure, Papez proposed (1) that the hypothalamus, the anterior thalamic nu-
clei, the cingulate gyrus, the hippocampus, and their interconnections may con-
stitute a harmonious mechanism that elaborates the functions of central emotions
21 6 THEORETICAL PERSPECTIVES
and participate in emotional expression; and (2) that the hypothalamic compo-
nent of the circuit might be mainly involved in functions of emotional evalua-
tion and of emotional expression, whereas the cortical component (namely, the
cingulate gyrus) might be involved in the elaboration of emotional experience.
The Papez model, suggesting that the psychological complexity of emotions
should correspond to an equally complex anatomical organization, was further
developed by McLean (1949, 1961), who coined the term "limbic system" to de-
note a highly interconnected set of subcortical and cortical structures, mainly in-
volved in vegetative and emotional functions. McLean (1986) further pushed the
analogy between the intrinsic organization of the emotional system and the
anatomical organization of the limbic system by suggesting that both systems
may be characterized by a phylogenetically determined hierarchical organization.
According to McLean (1986), the most primitive, drive-related forms of behav-
ior (such as the fight-flight reactions), which are present in phylogenetically old
species such as the reptilians, would be subsumed by the hypothalamus and by
the related parts of the paleostriatum. In contrast, the family-related patterns of
behavior (namely, nursing in connection with maternal care, audiovocal com-
munication for maternal-offspring contact, and play), which are characteristic
only of mammals, would be subserved by the cingulate gyrus, which is the phy-
logenetically more recent part of the limbic system.
Studies on Hemispheric Asymmetries in Emotional Representation
A set of different neuropsychological models have been advanced more recently

based on data suggesting that not only the cortical/subcortical (or the limbic/non-
limbic) dichotomy, but also the right hemisphere/left hemisphere distinction,
could be relevant to understanding the cerebral organization of emotions. Some
of these models (influenced in part by the importance attributed to cognitive fac-
tors in contemporary psychological theories of emotions) propose that the dif-
ferent cognitive styles of the right and left hemispheres may subserve this inter-
hemispheric difference. Tucker (1981, 1989) has suggested, for example, that
two cognitive features could favor the right, rather than the left, hemisphere in
the processing of emotional information: (1) the tendency to represent experi-
ence in an analogical (rather than in an arbitrary verbal) code; and (2) the abil-
ity to integrate information in a syncretic and holistic manner rather than treat-
ing it in a sequential, analytical fashion.
Following a similar line of thought, Ross (1981, 1984) has proposed that the
right hemisphere dominance for emotions (documented by many clinical and ex-
perimental data) may basically concern the communicative (rather than other
more elementary) components of emotions.
Other interpretations of the hemispheric asymmetries in emotional processing
have, on the contrary, been suggested by the different emotional behaviors shown
by patients subjected to pharmacological inactivation of the right and left hemi-

sphere (Alema & Donini, 1960; Perria, Rosadini, & Rossi, 1961; Terzian & Ce-
cotto, 1959). The earliest proponents of these models (Davidson et al., 1979;
Davidson & Fox, 1982; Rossi & Rosadini, 1967; Sackeim et al., 1982; Terzian
& Ceccotto, 1959) argued that a neuropsychological model of emotional valence
could explain many clinical and experimental data assuming a left-hemisphere
dominance for "positive" emotions and a right-hemisphere prevalence for "neg-
ative" emotions. More recent formulations of the same theory (Davidson, 1984,
1992; Davidson & Tomarken, 1989; Davidson et al., 1990) have shifted atten-
tion from the positive-negative to the approach-withdrawal dimension, which is
considered to be similar to the pleasantness dimension but could actually be more
consistent with some clinical and experimental data (for detailed accounts of the
various formulations of the "valence hypothesis," see Borod, 1992; Davidson,
1993; Heller, 1993).
Other more biologically oriented neuropsychological theories of emotion have
recently assumed that a phylogenetically determined hierarchical principle might
explain the different representations of emotions at the levels of the right and left
hemispheres. Thus, Ross et al. (1994) have proposed that the most primitive forms
of emotions, which usually have a negative valence, might be more strongly rep-
resented in the right hemisphere, whereas the most phylogenetically advanced
social forms of emotion might be mostly represented in the left hemisphere. In
contrast, Gainotti, Caltagirone, and Zoccolotti (1993; see also Gainotti, 1994,
1997) have proposed that the hierarchical principle that regulates the different
representations of emotion in the right and left hemispheres may concern differ-
ent levels of emotional processing rather than different categories of emotions.
The psychological model taken as reference by Gainotti et al. was Leventhal's
view (see Leventhal, 1979, 1984; Leventhal & Scherer, 1987) of emotions as a
hierarchically organized multilevel processing system. According to Leventhal,
this system has at bottom a basic set of innate neuromotor programs, at an in-
termediate level a set of learned automatic emotional schemata, and at the top a
processing system subserving functions of emotional conceptualization and emo-
tional control. Gainotti et al. suggested that the schematic level of emotional pro-
cessing may be mainly subserved by the right hemisphere and that the level of
emotional conceptualization and control might be mostly subsumed by the left
hemisphere.
Although space does not allow me to develop all the problems sketched in this
short historical introduction, I do dwell in more detail on some of them in ensu-
ing sections of this chapter. In particular, the issues that I take into account, be-
cause they play a critical role in neuropsychological theories of emotions, con-
cern (1) the relationships between the emotional and the cognitive systems, (2)
the main features that distinguish the emotional from the cognitive system, (3)
the componential nature of emotions, and (4) the hierarchical organization of the
2 I8 THEORETICAL PERSPECTIVES
emotional processing system. In my attempt to discuss these basic issues, I try

to focus attention more on human than on animal studies and to consider most
of the brain structures (or the main anatomical variables) that have attracted the
attention of authors interested in the study of the brain-emotion relationships in-
stead of focusing on just one.
CURRENT NEUROPSYCHOLOGICAL THEORIES OF HUMAN EMOTION
Shifts in Basic Assumptions About the Relationships Between

Emotional and Cognitive Systems
Implicit or explicit assumptions about the relationships between emotional and

cognitive systems changed considerably as studies of brain-emotions relationships
developed. In the earliest studies two sets of data had attracted the investigators'
attention: (7) the contrast between cognitive disorders resulting from lesions of
cortical areas and emotional disorders resulting from lesions of subcortical struc-
tures, and (2) the observation that integrated emotional outbursts can be observed
after disconnection of subcortical structures (subserving emotional expression)
from the influence of cortical inhibitory areas. The neuropsychological models
underlying these observations assumed that emotional and cognitive functions are
subserved by different brain structures and that the cognitive system usually keeps
the emotional system under control so that impulsive and socially disruptive forms
of emotional response do not assume control of overt behavior.
During several decades, the assumption that elementary emotional mechanisms
may be subserved by some subcortical brain structures seemed to be confirmed
by the observation that behavioral manifestations of emotions can be obtained
by stimulation of subcortical structures, such as the hypothalamus, the septal nu-
clei, and the amygdala (for reviews, see Brodal, 1981; Buck, 1976; Macchi, 1989).
The fact that similar expressive emotional displays could be obtained by stimu-
lation of cortical areas (such as the cingulate or the parahippocampal gyrus) was
not considered to be inconsistent with the hypothesis of subcortical localization
of the basic emotional mechanisms because these emotional manifestations were
interpreted as due to the afterdischarge provoked by the cortical stimulation over
the above-mentioned subcortical structures. Thus, the only change in this gen-
eral model until the 1970s was a progressive increase in the importance attrib-
uted to the amygdala for various aspects of emotional behavior, with a correla-
tive decrease in the role attributed to the hypothalamus for these functions (but
see Panksepp [1982] for a different viewpoint).
Furthermore, results of animal studies showing that electrical stimulation of
the amygdala usually provokes strong fear and anger reactions (Delgado, 1960;
Kaada, 1951; McLean & Delgado, 1953; Ursin & Kaada, 1960) were extrapo-
lated to humans, due to the observation that patients with epileptic foci localized
in the mesial parts of the temporal lobe often experience critical emotional phe-
nomena characterized by fear.
The neuropsychological model assuming that the basic command systems for
primitive fear-anger emotions are located in the amygdala became very popular
and had important medical and social implications. It was, in fact, assumed that
many instances of aggressive behavior were due, in epileptic patients, to the di-
rect action of a focus firing within the amygdala (Falconer et al., 1958;
Geschwind, 1974; Treffert, 1964; Walker, 1973) and that even non-ictal mani-
festations of aggression or of sociopathic behavior could result from a chronic
stimulation of the amygdala from a patent or covert epileptic focus (Walker,
1973). Even though more carefully controlled investigations by Gloor (1967),
Ounstead (1969), Gunn and Bonn (1971), and Rodin (1973) failed to confirm the
relationship between temporal lobe epilepsy and ictal or interictal aggressive be-
havior, the model survived, leading to the development of neurosurgical strate-
gies for treatment and control of aggressive behavior (Valenstein, 1973).
In more recent years, the model assuming that emotional and cognitive func-
tions must be subserved by quite different anatomical structures (and that the
amygdala may house elementary emotional mechanisms) has been in part re-
considered and substituted with the assumption that, at least in humans, emo-
tional and cognitive functions must be strongly reciprocally interconnected.
This new theoretical approach has been motivated by several factors. The
most important of these is the influence exerted by psychological theories of
emotion (Frijda, 1986, 1987; Lazarus, 1982, 1984; Scherer, 1984; see also
Scherer, Chapter 6, this volume) which have consistently claimed that a
process of cognitive appraisal constitutes the necessary prerequisite of any
emotional event. A second factor, discussed earlier, is the discovery that emo-
tions are not equally represented in the right and left hemispheres and the hy-
pothesis that this asymmetrical representation of emotions may be basically
due to cognitive factors. Finally, the hypothesis of an integrated, rather than
of an independent, representation of the emotional and cognitive systems has
been strengthened by more careful analyses of the effects of amygdala stim-
ulation in humans. These studies, recently reviewed by Halgren (1991) and
Gloor (1990), have consistently shown that the quality of experiential phe-
nomena provoked by stimulation of the amygdala or other temporolimbic
structures is not related to the exact electrode position but rather to the per-
sonality and the ongoing psychological problems of the patient.
The amygdala is, therefore, considered by some researchers to be an essential
point of integration of cognitive representations with affective significance rather
than as a structure subserving basic emotional mechanisms. On the other hand,
if in our search for structures in humans that house these basic emotional mech-
anisms, we come back from the amygdala to the hypothalamus, we see that le-
sions of this structure do not disrupt proper emotional functions. In a well-

controlled neuropsychological investigation, Weddell (1994) has, in fact, recently
shown that in patients with hypothalamic tumors, autonomic and endocrinolog-
ical disorders are very common, survival-appetitive disorders (concerning eat-
ing, drinking, and sexual behavior) are less frequent, but still common, whereas
personality disturbances and disorders of social-emotional communication are
very rare.
Both the amygdala and the hypothalamus seem, therefore, to subserve only
some fragments of the complex repertoire of physiological and behavioral pat-
terns that characterize the emotional schemata. To be sure, in humans, the amyg-
dala seems to play a prominent role in complex situations that require the inte-
gration of emotional and cognitive functions, whereas the hypothalamus seems
to regulate much more elementary autonomic and endocrinological functions as
well as basic survival-appetitive behaviors that are usually considered apart from
the properly emotional system.
Taken together, these data seem to suggest that emotions must be considered as
a multicomponent adaptive system spanning from very primitive and hard-wired
survival-related behavioral schemata to much more complex and learned behav-
ioral patterns, highly integrated with the cognitive system. The points, that play a
crucial role in this tentative general interpretation of the emotional system and that,
I intend to discuss in the next sections of this chapter mainly concern (7) the defin-
ing features of emotions, with special emphasis on the distinction between
emotional and cognitive systems; (2) the componential nature of the emotional pro-
cessing system; and (3) the hierarchical organization of emotions and the integra-
tion between emotional and cognitive systems.
The Defining Features of Emotions and the Distinction

Between Emotional and Cognitive Systems
Several authors have tried to identify some points of reference with which to dif-
ferentiate the behavioral schemata belonging to the conceptual field of emotions
from those belonging to contiguous but different conceptual areas. One very sim-
ple reference axis could be the duration of the behavioral pattern at issue. Ac-
cording to Ekman (1984), who has tried to analyze the problem with reference
to this axis, emotions are reactions that last several seconds and must be differ-
entiated from both very brief responses (such as the reflex reactions) and long-
lasting behavioral schemata (such as affects or personality traits).
A second important reference axis, which is more clearly linked with the main
line of thought followed in this chapter, refers to the complexity and the level of
phylogenetic development typical of the behavioral pattern taken into account.
From this point of view, emotions are behavioral reactions with an intermediate
level of complexity and can, therefore, be distinguished by (7) very simple, prim-
itive, and hard-wired behavioral patterns (such as reflex responses or some ba-
sic survival-related appetitive behaviors), and (2) more complex and learned cog-
nitive activities.
Because the most important controversies regarding human emotion, such as
the debate between Zajonc (1980, 1984) and Lazarus (1982, 1984), have con-
cerned the interface between the emotional system and the cognitive system, I
discuss here the main similarities and differences between the two. For simplic-
ity, it could be said that the general architectures of the two systems are similar,
but their specific scopes are different. As for the structural similarities, most au-
thors (e.g., Ekman, 1984; Gainotti, 1989, 1994; Leventhal, 1984; Oatley &
Johnson-Laird, 1985, 1987; Scherer, 1984) consider both the emotional and the
cognitive system as phylogenetically advanced adaptive systems based on inte-
grated work with several components aimed at (7) scanning the external milieu,
(2) selecting and analyzing the most relevant stimuli, (3) providing an appropri-
ate response to these stimuli, and (4) learning to give a subjective (emotional) or
objective (cognitive) meaning to these stimuli. As for the different scopes of the
emotional and cognitive systems, they will be considered first by looking at the
general logic of each system. The model proposed by Oatley and Johnson-Laird
(1985, 1987) is appropriate from this point of view because it suggests that the
organism has at its disposal two operative (the emotional and the cognitive) sys-
tems to face a partially unpredictable environment. The emotional system is
viewed, within this model, as an emergency system capable of interrupting on-
going action with an urgency procedure to rapidly select a new operative scheme.
The cognitive system is considered, on the contrary, to be a more complex and
advanced adaptive system, capable of exhaustively processing complicated situ-
ations and elaborating the strategies required to solve the problems raised by the
situations but needing much more time to carry out its work. According to Oat-
ley and Johnson-Laird (1985, 1987), the emotional system is based on a certain
number of modules (automata) that rapidly and automatically process a restricted
number of signals and trigger an immediate response, whereas the cognitive sys-
tem is based on more sophisticated modules and is supported by a propositional
structure, which allows a conscious and controlled analysis of information and
the selection of appropriate strategies. The major characteristics that distinguish
the emotional from the cognitive system are listed in Table 9.1.
The Componential Nature of the Emotional Processing System
The data in Table 9.1 introduce the problem of the componential nature of emo-
tions by showing that the specific scope of the emotional system strongly influ-
ences the manner in which this system processes ongoing information, selects
the most appropriate behavioral responses, learns to attribute meaning to a stim-
ulus category, and so on.
Table 9.1. Main Differences Existing Between the Emotional and the
Cognitive Systems
BEHAVIORAL OR
COGNITIVE DOMAIN EMOTIONAL SYSTEM COGNITIVE SYSTEM
Scanning of the external Automatic orientation Intentional orientation of

milieu and orientation elicited by attention at least, in part,
of attention external stimuli determined by internal
representations
Analysis of sensory data Quick computation of Exhaustive but slower
and computation of crude, poorly processed computation of highly
stimulus significance sensory data leading to processed information;
a direct motor response leads to gathering of
further information
about the stimulus
Behavioral motor Immediately selected The selection of the
response from a small number operative strategy results
of innate operative from a thorough analysis
patterns corresponding of the external situation
to the basic needs of and of information stored
the species in question; in long-term memory;
intervenes with an often requires the
emergency procedure, inhibition of the most
making very probable spontaneous motor
the achievement of the response
operative pattern
selected
Learning mechanisms Based on conditioned, Based on controlled and
automatic, and conscious acquisition of
unconscious learning information in declarative
memory
Level of autonomic A high activation of the A high level of autonomic
activation autonomic nervous activation can disturb the
system is a basic good functioning of the
component of emotions cognitive system
From the neuropsychological point of view, this functional architecture of the

emotional system raises the problem of the relationships between specific com-
ponents of emotions and underlying brain structures. Some efforts have there-
fore been made, in both animal and human studies, to map the main components
of emotion to discrete brain structures, and some of these studies have yielded
convincing results. In particular, several authors (e.g., Adolphs et al., 1994,1995;
Calder et al., 1996; Downer, 1961; Fuster & Uyeda, 1971; Jones & Mishk
1972; Nishijo, Ono, & Nishino, 1988; Ono et al., 1973; Young et al., 1995) have
shown that the amygdala could be the structure where the external stimuli are
computed by the emotional system. Furthermore, LeDoux (1986, 1987, 1989,

1993) has convincingly shown that the qualitative features of the emotional com-
putation of sensory data reported in Table 9.1 could be explained on the basis of
anatomical reasons, namely, the direct links existing between the thalamus and
the amygdala. Even the strongest supporters of the "cognitive" theories of emo-
tions, such as Mandler (1980) and Lazarus (1982, 1984), agree that a global,
rapid, and unconscious computation is sufficient to evaluate if an external situ-
ation can have a dangerous or a pleasant meaning for the individual. The sub-
cortical route directly linking the thalamus with the amygdala could transmit to
this structure the crude, poorly processed sensory data needed to make this sort
of computation immediately.
Other authors have shown that the hypothalamus could be crucially involved
in the regulation of the autonomic components of emotions (for reviews, see
LeDoux, 1987; Smith & DeVito, 1984), and these data have been recently con-
firmed by the study of Weddell (1994) on patients with brain tumors selectively
involving the hypothalamus or other brain structures, discussed earlier.
Less clear-cut are data concerning other structures usually considered to be in-
volved in the expression of emotions or in the control of their spontaneous ex-
pression. Thus, the ventral striatum, the ventral pallidum, and more generally the
basal ganglia have been considered to be involved in the execution of the emo-
tional responses for both anatomical and clinical reasons. From the anatomical
point of view, these structures receive strong afferents from the amygdala, the
hippocampus, and other limbic structures and send projections to cortical, sub-
cortical, and brain stem components of the motor system (De Long et al., 1984;
Graybiel, 1984; Krettek & Price, 1978; Mogenson, 1987; Nauta & Domesick,
1984). From the clinical point of view, patients with a degenerative disease of
the basal ganglia (e.g., Parkinson's disease) typically have "masked fades," that
is, a reduced propensity to make spontaneous facial emotional expressions (Broz-
gold et al., 1998; Buck & Duffy, 1980; Katsikitis & Pilowsky, 1991; Smith,
Smith, & Ellgring, 1996) and a similar inability to communicate affects with the
prosodic contours of speech (Borod et al., 1990; Critchley, 1981). Furthermore,
analogous defects in facial and vocal expression of emotions have been reported
by some authors (e.g., Cancelliere & Kertesz, 1990; Cohen, Riccio, & Flannery,
1994) in stroke patients with lesions involving the basal ganglia. The specificity
of these expressive emotional disturbances, however, has been questioned by
studies showing that not only the expression but also the comprehension of emo-
tional stimuli is impaired in patients with vascular (Cancelliere & Kertesz, 1990),
neoplastic (Weddell, 1994), or degenerative (Blonder, Gur, & Gur, 1989; Speedie
et al., 1990) disease of the basal ganglia.
A very similar picture can be obtained if we pass from the basal ganglia to the
frontal lobes (and in particular to the fronto-orbital cortex), which, according to
most authors, play a major role in the intentional control of the emotional ex-
pressive apparatus and in the inhibition of socially unacceptable emotional dis-

plays (for review, see Stuss & Benson, 1986).
Recent neuropsychological investigations have, in fact, confirmed that patients
with frontal lobe damage are very impaired in the production of facial emotional
expressions, both intentionally (Caltagirone et al., 1989a; Weddell, Miller, & Tre-
varthen, 1990) and in response to emotional stimuli (Borod et al., 1985; Wed-
dell, Miller, & Trevarthen, 1988). As in the case of studies conducted on patients
with lesions involving the basal ganglia, however, the specificity of expressive
emotional defects resulting from frontal lobe injury is at present also controver-
sial. Although some studies have shown that a lesion of the frontal lobes does
not significantly affect the comprehension of facial emotional expressions (Kolb
& Taylor, 1981; Prigatano & Pribram, 1982), other authors have shown that
frontal lesions may influence not only the production but also the comprehen-
sion of facial emotional expressions (Hornak, Rolls, & Wade, 1996; Weddell,
1989, 1994). The theoretical problem raised by these data could be very impor-
tant because both the frontal lobes and the basal ganglia are usually considered
to be components of the motor/executive system rather than of other systems in-
volved in the processing of (emotional or cognitive) information.
A conservative position could, therefore, consist of assuming that method-
ological reasons (concerning either the patients or the material used to test the
comprehension of emotional material), in part, explain these unexpected data. As
a matter of fact, a methodological problem common to all the tasks used to in-
vestigate the comprehension of emotional stimuli in brain-damaged patients is
the fact that the kind of information processing requested by these tasks corre-
sponds much more to a cognitive than to an emotional computation. Almost all
these tasks, in fact, require one to decide if the emotion expressed by a given
face or a given voice belongs, for example, to the category "fear" or to the cat-
egory "anger," but this kind of computation of the sensory data can hardly be
considered as emotional if we refer to the criteria reported in Table 9.1. Fur-
thermore, because the expressive features that allow this sort of categorization
are generally unknown to the patients, emotional comprehension tasks often are
both perceptually and cognitively demanding. Taken together, these reasons sug-
gest that results obtained from emotional comprehension tasks performed by
brain-damaged patients be interpreted with caution.
The Hierarchical Organization of the Emotional System
I have repeatedly made a number of assumptions in this chapter based implic-

itly on a neurobiological model of emotion whose main points can be summa-
rized as follows:
(1) Emotion must be considered as a nonhomogeneous, hierarchically orga-
nized, multicomponent adaptive system. (2) This system has partly changed its
nature during phylogenetic evolution because it originally had the functions of

an automatic emergency system but later developed more and more important
links with the propositional cognitive system. (3) Behavioral patterns included
under the heading of "emotion" span, accordingly, from a small set of hard-wired
survival-related behavioral schemata, mainly related to social interactions, to a
large number of learned complex behavioral patterns, highly integrated with the
cognitive system. (4) The neuropsychological theories of emotion discussed in
this chapter often differ as a function of the lower (automatic) or higher (more
cognitive) part of the emotional system taken into account by different authors.
This neurobiological model of emotion finds its psychological counterpart in the
perceptual-motor theory of emotion developed by Leventhal (1974, 1979, 1984),
which makes the following assumptions: (7) Every emotion is formed by different
components and is based on operations arising at various levels. (2) The emotional
processing system is hierarchically organized. (3) This hierarchical organization is
the result of a construction made by the individual during his developmental his-
tory. According to Leventhal, the lowest level of the system is formed by a set of
innate neuromotor programs. Each of these programs corresponds to a basic emo-
tion and generates a specific pattern of expressive (behavioral and autonomic) re-
actions and of concomitant subjective feelings in response to specific releasing
stimuli. With the individual's ontogenetic development, this basic sensorimotor
structure becomes incorporated into two different memory systems corresponding
to two different levels of emotional processing: the schematic level and the con-
ceptual level. The schematic level is based on a mechanism of conditioned learn-
ing and is formed by the analog records of the conditions in which a given envi-
ronmental situation has been associated with the generation of a given neuromotor
program (and of the corresponding emotional experience). Memories stored in this
system are, therefore, formed by the syncretic association between a given stim-
ulus and the resulting expressive reaction, including the concomitant subjective
feelings. These memories are automatically reactivated during a new encounter
with the eliciting situation, generating a spontaneous, felt emotion.
The conceptual level, on the other hand, is based on the functioning of the se-
mantic declarative memory system and contains a set of abstract propositions
about emotions rather than a set of felt memories. These abstract propositions
mainly concern stored knowledge about emotion-provoking situations and social
rules stating how to respond appropriately (i.e., deliberately rather than sponta-
neously) to these situations. This system is, therefore, involved in the cognitive
evaluation of the emotional meaning of complex situations and in the develop-
ment of intentional control over the emotional expressive apparatus. Even if, ac-
cording to Leventhal, both the schematic and the conceptual levels are involved
in each emotional response and only the degree of their involvement varies ac-
cording to individual and sociocultural factors, the neuroanatomical substrates of
these two levels should be different. The schematic level should mainly rely on
subcortical circuits and structures (and in particular on the interconnections be-

tween the hypothalamus and amygdala), whereas the conceptual level should be
mostly based on the cortical functions of cognitive appraisal and of behavioral
control. Some authors have, however, suggested that this could not be the whole
story and that, in addition to the distinction between subcortical and cortical struc-
tures, one should also consider the differences between the right and left hemi-
spheres in this search for the neuroanatomical substrates of the schematic and
conceptual levels of emotional processing.
To be sure, Buck (1984), Gainotti, Caltagirone, and Zoccolotti (1993), and
Lamendella (1977) have suggested that the two sides of the brain could play a
complementary role in emotional behavior, the right hemisphere being more in-
volved in the automatic (expressive and autonomic) components of emotion and
the left hemisphere in functions of control and of modulation of spontaneous
emotional expression.
Data suggesting that the right hemisphere may have a prominent role in vari-
ous aspects of emotional behavior, and in particular in the generation of the ex-
pressive and autonomic components of spontaneous emotions, have been reviewed
elsewhere (e.g., Borod, 1993; Borod, Santschi Haywood, & Koff, 1997; Gainotti,
1996, 1997; Gainotti, Caltagirone, & Zoccolotti, 1993; Wittling, 1995). I there-
fore do not think it necessary to take them into account here. I think it useful, on
the contrary, to briefly discuss the complementary hypothesis that assumes that
the left hemisphere may play a critical role in functions of emotional control.
Three independent lines of evidence seem to support this hypothesis. The first
is the observation that left brain-damaged patients (and in particular those with
Broca's aphasia) often show an excess of emotional reactivity, which renders them
at least, in part, similar to patients with bilateral corticobulbar lesions. This simi-
larity has been pointed out by Horenstein (1970) and by Gainotti (1972, 1983).
The former stressed the emotional lability of aphasic patients, noting that they eas-
ily cry when exposed to (happy or sad) emotionally laden stimuli. The latter noted
that the sudden crying spells of patients with Broca's aphasia resemble in some
ways the paroxysmal outbursts of crying of patients with a pseudobulbar state. This
clinical impression has been studied more thoroughly by House et al. (1989), who
focused on the manifestations of emotionalism in stroke patients. These authors
showed that sudden episodes of uncontrollable outbursts of crying are often ob-
served in patients with left frontal lesions, suggesting that the anterior regions of
the left hemisphere may play a critical role in functions of emotional control.
The second line of evidence consists of the observation, reported by Heilman,
Schwartz, and Watson (1978) and by Meadows and Kaplan (1994), that the veg-
etative (electrodermal) response to emotional stimuli is higher in left brain-
damaged patients than in normal controls. Although these data have not been
confirmed by other authors (e.g., Caltagirone et al., 1989b, Morrow et al., 1981;
Zoccolotti et al., 1986), they suggest that, at least in certain groups of left
brain-damaged patients, the defect of cortical control may provoke not only an
accentuation of the expressive behavioral reaction but also an increased vegeta-
tive response to emotional stimuli.
Finally, a third group of data that could be compatible with the hypothesis of left
hemisphere dominance for the intentional control of the facial expressive apparatus
is the difference between the right and left halves of the face in the production of
positive and negative emotional expressions. Although most authors who have stud-
ied this problem have shown a greater expressivity of the left hemiface for all types
of emotions (for reviews, see Borod & Koff, 1984; Borod, Santschi Haywood, &
Koff, 1997; Gainotti, 1989), some authors have shown greater expressivity of the left
(with respect to the right) hemiface for negative emotions but not for smiling or for
other positive emotions (Borod & Caron, 1980; Sackeim & Gur, 1978; Schwartz,
Ahern, & Brown, 1979). The literature dealing with normal adult facial asymmetry
during emotional expression and with the stronger asymmetries found for negative
emotions has been reviewed in detail by Borod, Santschi Haywood, and Koff (1997).
These data have generally been discussed in the context of the hypothesis that
assumes different hemispheric specialization for positive and negative emotions,
but Etcoff (1986) has rightly noted that there are other possible interpretative
contexts. Smiling differs, in fact, from other emotional facial expressions not
only because of the positive polarity of the emotion it usually expresses but also
because it represents the emotional facial expression easiest to reproduce volun-
tarily and most currently used for approach and for social communication. A
dominance of the left hemisphere in the intentional control of the expressive fa-
cial apparatus could, therefore, counterbalance the "natural" expressivity of the
left hemiface, resulting from the general superiority of the right hemisphere in
the spontaneous expression of emotions. A very similar interpretation of the dif-
ferences between the right and left halves of the face in the expressions of pos-
itive and negative emotions has been advanced by Buck (1984) and by Rinn
(1984) in a model that also stresses the possible dominance of the left hemisphere
for functions of emotional control. According to these authors, the greater asym-
metry between the left and right halves of the face in the expression of negative
emotions could be due to the greater inhibition exerted in this case on the right
half of the face by the left hemisphere to attenuate the overt expression of so-
cially censurable negative emotions. The lesser degree of asymmetry presented
by smiling could be due to the fact that this form of "emotional" expression is
used for social purposes and is not inhibited by the left hemisphere.
Possible Relationships Between the Left/Right and the

Cortical/Subcortical Dichotomies in the Study of Human Emotion
Studies of hemispheric asymmetries in representation and control of emotions

(and in particular the model assuming right-hemisphere dominance for automatic,
spontaneous emotions and left-hemisphere prevalence for emotional control) raise

some important questions about the relationships between hemispheric and sub-
cortical levels of emotional representation. With reference to the excellent chap-
ter of Tucker, Derryberry, and Luu (Chapter 6, this volume), which underlines
the strong interactions that develop between cortical and subcortical mechanisms
during the process of encephalization, we could ask if hemispheric asymmetries
in representation and control of emotions are mostly due to asymmetrical
bottom-up or top-down processes.
In the first case, the hemispheric asymmetries for emotional functions could
be due to a greater emotional involvement of the right-hemisphere subcortical
structures, whereas in the second case, they could be due to a left-hemisphere
cortical dominance for cognitive and control functions. To test the first hypoth-
esis experimentally, some authors have tried to generate data from animal stud-
ies to support a greater role of the right-hemisphere subcortical structures, and
in particular of the amygdala, in emotional function. These data are, however,
controversial because Coleman-Mesches, Salinas, and McGaugh (1996; see also
Coleman-Mesches & McGauch, 1995a-c) have obtained results suggesting a
prevalence of the right amygdala for emotional functions in the rat, but other
studies (Coleman-Mesches, West, & McGaugh, 1997; LaBar & LeDoux, 1996;
LaBar et al., 1995) have found no difference between the right and left amyg-
dala for other aspects of emotional functioning.
The second hypothesis is perhaps more speculative and difficult to submit to
strong empirical control, but it is substantially accepted by most authors and sup-
ported by clinical and experimental data. This hypothesis, which assumes that
the development of language in the left hemisphere may have greatly increased
the capacity of intentional control of this hemisphere, is consistent with Luria's
views (1966) on the regulatory role of language on various aspects of human be-
havior and with Gazzaniga's studies (1995) on the cognitive capacities of the
isolated right and left hemispheres in split-brain patients. This author has, in fact,
shown that the left hemisphere is surprisingly superior to the right hemisphere
not only in linguistic tasks but also in apparently nonverbal tasks requiring or-
ganization and control functions.
Finally, the hypothesis of greater involvement of the left hemisphere in func-
tions of intentional control is consistent with the interpretation recently proposed
by Gainotti (1993,1996) of the unilateral neglect syndrome, very typical of right-
hemisphere lesions. Drawing on evidence suggesting that the neglect syndrome
may be due to a selective disruption of the automatic components of the spatial
orienting of attention, Gainotti (1993, 1996) proposed that the automatic and the
controlled components of the spatial orienting mechanisms may be subserved re-
spectively by the right and the left hemispheres. Both in attention-orienting and
in emotional functions, automaticity could, therefore, be a main feature of the
right hemisphere and intentional control the hallmark left hemisphere function-
ing. The hypothesis that the right hemisphere may preferentially subserve the au-
tomatic "schematic level" and the left hemisphere the controlled "conceptual
level" of emotional processing seems, therefore, consistent with the basic re-
quirement of an internal coherence between the principles of organization un-
derlying respectively the emotional system and the right and left hemispheres.
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IV
EMOTIONAL DISORDERS
10
Elation, Mania, and Mood Disorders:
Evidence from Neurological Disease
ROBERT G. ROBINSON AND

FACUNDO MANES
The first reports of emotional disorders associated with brain damage (usually
caused by cerebrovascular disease) were made by neurologists and psychiatrists
in case descriptions. Meyer (1904), for example, wrote that mood disorders fol-
lowing brain injury were probably the result of a combination of social, psy-
chological, and biological factors. He proposed that in some cases there may be
relationships between particular "traumatic insanities," such as delirium or de-
mentia, and specific locations and causes of brain injury. Babinski (1914) noted
that patients with right-hemisphere disease frequently displayed the symptoms
of anosognosia, euphoria, and indifference. Bleuler (1951) wrote that, after stroke,
"melancholic moods lasting for months and sometimes longer appear frequently."
Kraepelin (1921) recognized a frequent association between manic depressive in-
sanity and cerebrovascular disease and thought that, in some cases, the athero-
sclerotic disease produced the mood disorder.
Goldstein (1939) was the first to describe an emotional mood disorder thought
to be uniquely associated with brain disease: the catastrophic reaction. The cat-
astrophic reaction is an emotional outburst involving various degrees of anger,
frustration, depression, tearfulness, refusal, shouting, swearing, and sometimes
aggressive behavior. Goldstein (1939) ascribed this reaction to the inability of
the organism to cope when faced with a serious defect in its physical or cogni-
tive functions. In his extensive studies of brain injury in war, Goldstein (1942)
239
240 EMOTIONAL DISORDERS
described two symptom clusters: those related directly to physical damage of a

circumscribed area of the brain and those related secondarily to the organism's
psychological response to the injury. Emotional symptoms, therefore, represented
the latter category (i.e., the psychological response of an organism struggling
with physical or cognitive impairments).
A second abnormality unique to brain injury, also involving a disturbance (this
time an absence) of mood, was the indifference reaction described by Hecaen,
deAjuriaguerra, and Massonet (1951) and Denny-Brown, Meyer, and Horsen-
stein (1952). The indifference reaction associated with right-hemisphere lesions
consists of symptoms of indifference toward failures, lack of interest in family
and friends, enjoyment of foolish jokes, and minimization of physical difficul-
ties. It is associated with neglect of the left half of the body and space.
A third "mood" disorder uniquely associated with brain injury is pathological
laughing or crying. Ironside (1956) described the clinical manifestations of this
disorder. Such patients' emotional displays were characteristically unrelated to
their inner emotional state. Crying, for example, may occur spontaneously or af-
ter some seemingly minor provocation. This phenomenon has been given vari-
ous names, such as emotional incontinence, emotional lability, pseudobulbar af-
fect, and pathological emotionalism.
The first systematic study to contrast the mood disorders of patients with right-
and left-hemisphere brain damage was done by Gainotti (1972). He reported that
depressive catastrophic reactions were more frequent among patients with left-
hemisphere brain damage, particularly those with aphasia, than among patients
with right-hemisphere lesions. Gainotti agreed with Goldstein's explanation
(1942) that it was a desperate reaction of the organism when confronted with a
severe physical disability. The indifference reaction, on the other hand, was not
easy to understand. Gainotti (1972) suggested that denial of illness and organi-
zation of the nonverbal type of synthesis may play an important role in this emo-
tional disorder.
In conclusion, there have been two primary lines of thought in the study of
emotional disorders that are associated with structural brain disease. One attri-
butes mood disorders to an understandable psychological reaction to the associ-
ated impairment; the other, based on a lack of association between severity of
impairment and severity of emotional disorder, suggests a direct causal connec-
tion between emotional disorders and structural brain damage.
ELATION AND MANIA ASSOCIATED WITH STROKE
Mania is a relatively rare consequence of acute stroke lesions. Although preva-

lence studies have not been conducted, Robinson et al. (1988) reported that less
than 1% of patients with acute stroke have mania. Most of the patients included
Elation, Mania, and Mood Disorders 241
in studies of mania following stroke present with manic symptoms and are only
secondarily found to have brain injury. These patients, however, have typical
manic syndromes, and their symptoms are not significantly different from those
of patients with mania who do not have brain injury (Starkstein et al., 1987a).
Relationship to Lesion Location
Cummings and Mendez (1984) reported two patients who developed mania after
right thalamic infarcts and reviewed the case literature, which suggested an asso-
ciation of mania with right-hemisphere lesions. Based on a series of 17 patients
with post-brain-injury mania, Robinson et al. (1988) reported a significantly in-
creased frequency of right-hemisphere lesions compared with 31 major depressed
patients and 28 nonmood-disordered controls (Fig. 10.1). These lesions involved
the basal and polar areas of the right temporal lobe as well as subcortical areas of
the right hemisphere, such as the head of the caudate and right thalamus.
In another study, Starkstein et al. (1990b) used positron emission tomography
(PET) with 18-fluorodeoxyglucose to examine the metabolic abnormalities in
Figure 10.1. The percentage of patients with mania, major depression, or no mood dis-
order after brain injury, divided by lesion location as visualized on CT scan. Mania was
strongly associated with right-hemisphere lesions and major depression with left-
hemisphere injury. (Data are from Robinson et al., 1988.)
three patients with mania following right basal ganglia strokes. These patients
were found to have focal hypometabolic deficits in the right basotemporal cor-
tex. This finding suggested that lesions that lead to secondary mania may do so
through their distant effects on the right basotemporal cortex. This phenomenon,
called diaschisis (i.e., lesions producing distant effects), is a well-recognized con-
sequence of brain injury.
Risk Factors for Mania Following Stroke
Because not every patient with a right orbitofrontal or basotemporal lesion devel-
ops a manic syndrome, the question arises as to whether there are potential pre-
disposing factors for secondary mania (Robinson et al., 1988; Starkstein et al.,
1987a). Patients with secondary mania were found to have a significantly higher
frequency of familial history of psychiatric disorders, as well as significantly more
subcortical brain atrophy (as determined by increased ventricular to brain ratios)
than did patients with similar brain lesions but without mania. Interestingly, sec-
ondary mania patients without a genetic predisposition had significantly more sub-
cortical atrophy than secondary mania patients with a family history of mood dis-
order, suggesting that subcortical atrophy and genetic predisposition may be
independent risk factors for mania following brain injury (Starkstein et al., 1987a).
Mechanism
To postulate a mechanism for secondary mania, two clinicopathological correla-

tions need to be explained. First, most lesions associated with secondary mania
involved (directly or indirectly) a limbic or limbic-related area of the brain. Sec-
ond, virtually all of these lesions were localized to the right hemisphere.
Several studies have demonstrated that the amygdala (located in the limbic
portion of the temporal lobe) plays an important role in the production of in-
stinctive reactions and the association between stimulus and emotional response
(Gloor, 1986). The amygdala receives its main afferents from the basal dien-
cephalon (which in turn receives psychosensory and psychomotor information
from the reticular formation), and the temporopolar and basolateral cortices
(which receive main their afferents from heteromodal association areas) (Beck,
1949; Crosby, Humphrey, & Laner, 1962). The basotemporal cortex receives af-
ferents from associated cortical areas and the orbitofrontal cortex, and it sends
efferent projections to the entorhinal cortex, hippocampus, and amygdala. By
virtue of these connections, the basotemporal cortex may represent a cortical link
between sensory afferents and instinctive reactions (Goldar & Outes, 1972).
The orbitofrontal cortex can be subdivided into two regions: a posterior one,
which is restricted to the limbic functions and should be considered part of the
limbic system; and an anterior one, which exerts a tonic inhibitory control over
the amygdala by means of its connection through the uncinate fasciculus with
the basotemporal cortex (Nauta, 1971). Lesions or dysfunction of these areas may
result in motor disinhibition (e.g., hyperactivity, pressured speech), intellectual
disinhibition (e.g., flight of ideas, grandiose delusions), and instinctive disinhi-
bition (e.g., hyperphagia and hypersexuality).
The second finding that needs to be incorporated into an explanation of ma-
nia following stroke is that it almost always occurs following right-hemisphere
lesions. Laboratory studies of the neurochemical and behavioral effects of brain
lesions in rats found that small suction lesions in the right (but not the left) frontal
cortex of rats produced a significant increase in locomotor activity (Robinson,
1979). Similar abnormal behavior was also found after electrolytic lesions were
made in the right (but not left) nucleus accumbens (which is considered part of
the ventral striatum) (Kubos, Moran, & Robinson, 1987). Moreover, right fron-
tocortical suction lesions also produced a significant increment in dopaminergic
turnover in the nucleus accumbens that was not seen with left-hemisphere lesions
(Starkstein et al., 1988). Thus, it is possible that in the presence of predisposing
factors, such as a genetic burden or subcortical atrophy, a significant increment
in biogenic amine turnover in the nucleus accumbens produced by specific right-
hemisphere lesions may be part of the mechanism that results in manic syndrome.
A case report (Berthier et al., 1990) suggested that the mechanism of secondary
mania was not related to the release of transcallosal inhibitory fibers (i.e., the re-
lease of left limbic areas from tonic inhibition due to a right-hemisphere lesion).
A patient who developed secondary mania after bleeding from a right basotem-
poral arteriovenous malformation underwent a Wada test before the therapeutic
embolization of the malformation. Amytal injection in the left carotid artery did
not abolish the manic symptoms (which would be the expected finding if the "re-
lease" theory were correct).
In conclusion, secondary mania is a rare complication of stroke lesions. Three
risk factors for mania following stroke have been identified: (1) a family history
of psychiatric disorders (Robinson et al., 1988), (2) increased subcortical atro-
phy (Starkstein et al., 1987a), and (3) seizure disorder (Shukla et al., 1987). Most
patients with secondary mania have right-hemisphere lesions, which involve the
orbitofrontal and/or basotemporal cortex, or subcortical structures such as the
thalamus or head of the caudate. Secondary mania may result from disinhibition
of dorsal cortical and limbic areas, dysfunction of asymmetrical biogenic amine
pathways, or both.
Treatment
Although no systematic treatment studies of secondary mania have been con-

ducted, one report suggests several potentially useful treatment modalities. Bak-
chine et al. (1989) carried out a double-blind, placebo-controlled treatment study
of a single patient with secondary mania. Clonidine (600 /Ag/day) rapidly re-
versed the manic symptoms, whereas carbamazepine (1200 mg/day) was associ-
ated with no mood changes, and levodopa (375 mg/day) was associated with in-
creased manic symptoms. Other treatment modalities, such as antiepileptic drugs
(valproate and carbamazepine), neuroleptics, and lithium, have been reported to
be useful for secondary mania (Robinson et al., 1988). None of these treatments
has been evaluated in double-blind, placebo-controlled studies.
MANIA ASSOCIATED WITH TRAUMATIC BRAIN INJURY
Prevalence
Mania is more frequent among patients with traumatic brain injury (TBI) than
among patients with stroke lesions (Jorge et al., 1993c; Robinson et al., 1988;
Shukla et al., 1987). In a study of 66 patients with acute TBI, 6 (9%) had sec-
ondary mania (Jorge et al., 1993c). One of these patients (17%) presented a bipo-
lar course. The manic episodes, however, were short-lived, with a mean duration
of 2 months. The mean duration of the elevated mood (i.e., elation), without meet-
ing other diagnostic criteria for mania, however, was 5.7 months. In addition,
three of the six secondary mania patients developed brief episodes of violent be-
havior at some point during the 1-year follow-up period. Aggressive behavior
was significantly more frequent in the secondary mania group than among pa-
tients who did not experience an affective disorder. At the time of the diagnosis,
three patients were receiving drug treatment (two patients received lorazepam,
and one patient, haloperidol); however, the duration of mania did not appear to
be significantly different between those who were and were not treated.
Relationship to Impairment Variables
In the study of six patients with mania following TBI, the severity of mania was
not associated with severity of brain injury, degree of physical or cognitive im-
pairment, frequency of personal or family history of psychiatric disorder, or qual-
ity of social functioning (Jorge et al., 1993c). Shukla et al. (1987) reported on
20 patients who developed mania following TBI. The clinical correlates were se-
vere head trauma in 13 of 20, partial seizures in 8 patients and generalized seizures
in 2, and irritable mood in 17 of 20. There was no family history of bipolar dis-
order, and 14 of the 20 had recurrent mania without depression. Thus, although
further studies of the relationships between impairment or risk factors and the
development of mania need to be conducted, the present data suggest that ma-
ma is not a response to the associated impairments and that seizure disorder may
play a role in the etiology of post-TBI mania.
The Jorge et al. (1993c) study of secondary mania syndromes found that the ma-
jor correlate of mania was the presence of anterior temporal lesions. This finding
was consistent with the finding in patients with stroke that mania was associated
with right basotemporal lesions. The trauma study did not have sufficient numbers
of patients with unilateral lesions to examine the right-hemisphere versus left-hemi-
sphere effect. Factors such as personal history of mood disorders or post-traumatic
epilepsy did not appear to significantly influence the frequency of secondary ma-
nia in this group of patients. Furthermore, although Shukla et al. (1987) did not
find a lateralized effect of seizure disorder on mania, the electroencephalographic
abnormalities had a temporal lobe focus in nine of ten seizure patients.
Mechanism
It has been suggested that the development of abnormal electrical activation pat-
terns in limbic networks, functional changes in aminergic inhibitory systems, and
the presence of aberrant regeneration pathways may play important roles in the
genesis of mania (Cseraansky et al., 1988; Stevens, 1990).
BIPOLAR DISORDER ASSOCIATED WITH STROKE OR TRAUMA
Starkstein et al. (1991) studied 19 patients with a diagnosis of secondary mania.

Seven of these patients had previously met Diagnostic and Statistical Manual of
Mental Disorders, Third Edition, Revised (DSM-III-R), criteria for the organic
mood syndrome of depression. The remaining 12 patients had mania without
prior depression. All the patients had computed tomographic (CT) scan evidence
of vascular, neoplastic, or traumatic brain lesion and no history of other neuro-
logical, toxic, or metabolic conditions.
There were no significant between-group differences in age, sex, race, educa-
tion, handedness, or personal history of psychiatric disease. Also, no significant
differences were found on neurological examination. On psychiatric examina-
tion, which was carried out during the index manic episode, no significant dif-
ferences were observed in the types or frequencies of manic symptoms. The bipo-
lar group, however, showed significantly greater intellectual impairment as
measured by Mini-Mental State Examination scores (P < 0.05). Patients with
bipolar disorder also had lesions restricted to the right hemisphere, which in-
volved subcortical structures including the head of the caudate or thalamus. One
patient developed a bipolar illness after surgical removal of a pituitary adenoma.
In contrast to these subcortical lesions, most of those in the unipolar mania group
had lesions involving the right basotemporal and orbitofrontal cortex (Fig. 10.2).
Figure 10.2. Lesion location in patients with bipolar mood disorder or mania without de-
pression after stroke, traumatic brain injury, or surgical lesions. Patients with bipolar dis-
order had a significantly greater frequency of subcortical (basal ganglia or thalamus) le-
sions than did patients with mania alone, who had more cortical lesions. Only two patients
had mixed cortical and subcortical lesions.
Shukla et al. (1987) did not examine cortical versus subcortical lesion loca-
tion, but the fact that 70% of the 20 patients had only manic episodes is consis-
tent with the hypothesis that cortical lesions lead to unipolar disorder (manic
unipolar) because TBI tends to be predominantly cortical in location.
The causes of both bipolar and unipolar mood disorder remain unknown. Pap-
pata et al. (1987) reported that subcortical lesions induce hypometabolic effects in
many regions, including contralateral brain areas (i.e., crossed-hemisphere and
crossed-cerebellar diaschisis). It is, therefore, possible that subcortical lesions may
induce metabolic changes in left frontocortical regions, which are associated with
depression. Mania may develop at a later stage, when these changes become re-
stricted to the orbitofrontal and basotemporal cortices of the right hemisphere.
DEPRESSION ASSOCIATED WITH STROKE
Depression is probably the most common emotional disorder associated with

stroke. Utilizing structured psychiatric interviews and established diagnostic cri-
teria, researchers have usually identified two forms of depressive disorder asso-
elated with brain disease. One type is major depression as defined by the DSM-
IV criteria for depression due to stroke with major depressive-like episode. The
second type of depression is dysthymic depression as defined by the DSM-III
(excluding the 2 year duration criterion and the exclusionary organic factor) or
the DSM-IV research criteria for minor depression.
The prevalences of these depressions vary, depending on the setting in which
patients are studied as well as on the nature and location of the brain injury. In
a study of 103 consecutive patients admitted to the hospital with acute cere-
brovascular lesions, we found that 27% met symptom criteria for major de-
pression, and 20% met symptom criteria for dysthymic (minor) depression
(Robinson et al., 1983b). Most other studies of patients hospitalized (in acute
care or rehabilitation hospitals) with cerebrovascular lesions have reported sim-
ilar frequencies of major depression (range ll%-27%) and minor depression
(range 20%-40%). The frequency of depression in community settings, how-
ever, appears to be lower. House et al. (1990b) found that 11% had major and
12% had other types of depression among 89 community patients examined dur-
ing the first month post-stroke. Burvill et al. (1995) found that 15% of 294 com-
munity patients with acute stroke had major depression and 8% had minor de-
pression.
Longitudinal Course of Depression
The longitudinal course of post-stroke depression has been investigated by our

group (Robinson, Bolduc, & Price, 1987) as well as by Morris, Robinson, and
Raphael (1990) and Astrom, Adolfsson, and Asplund (1993). In our study, all
patients with major depression recovered fully 1-2 years post-stroke. Minor de-
pression, however, had a less favorable prognosis, with only 30% having recov-
ered by 2 years post-stroke (half of the minor depressed patients had developed
major depression). In addition, about 30% of patients who were not depressed at
the initial hospital evaluation became depressed after discharge. Morris, Robin-
son, and Raphael (1990) found that, among a group of 99 patients in a stroke re-
habilitation hospital, those with major depression had a duration of illness of 40
weeks, whereas those with adjustment disorders (minor depression) had a dura-
tion of depression of only 12 weeks. Astrom, Adolfsson, and Asplund (1993)
showed that the majority of patients with acute-onset major depression recov-
ered by 1 year (8 of 14), but, among those who were still depressed, only one of
the six had recovered by 3 years.
In summary, the available data suggest that post-stroke depression is not a tran-
sient but a long-standing disorder with a usual natural course of somewhat less
than 1 year for major depression and perhaps a more variable course for minor
depression. Some major depressions last more than 3 years, and some minor de-
pressions evolve into major depression and may last for several years.
Relationship to Impairment
Although many clinicians have assumed that the most powerful determinant of
depression after stroke was the severity of associated physical impairment, em-
pirical studies have consistently failed to find a strong relationship between sever-
ity of depression and severity of physical impairment (Eastwood et al., 1989,
Morris, Robinson, & Raphael, 1990; Robinson et al., 1983b). This is not to say,
however, that there is no relationship. Numerous studies have demonstrated that
severity of physical impairment correlates with severity of depression and, in
some subpopulations, may be an important contributing factor to depression (As-
trom, Adolfsson, & Asplund, 1993; Eastwood et al., 1989; Morris et al., 1992b;
Robinson et al., 1983b).
Although the effect of impairment on depression appears to be fairly weak in
most patients, there is considerable evidence that depression adversely affects
post-stroke recovery in activities of daily living (ADL). Parikh et al. (1990) com-
pared 25 patients with post-stroke depression (either major or minor depression)
and 38 stroke patients with no mood disorders who were matched for severity of
ADL impairments in the hospital. After controlling for many of the variables that
have been shown to influence stroke outcome (such as acute treatment on a stroke
unit; size, nature, and location of brain injury; age; education; recurrent stroke
or other medical illness; and duration of rehabilitation services), patients with in-
hospital post-stroke depression were found to have a significantly poorer recov-
ery than nondepressed stroke patients at 2 years follow-up (Fig. 10.3).
Several studies have found that patients with major depression after left-
hemisphere stroke lesions had significantly greater cognitive deficits than non-
depressed patients with brain lesions of a similar size and location (House et al.,
1991; Robinson et al., 1986; Starkstein et al., 1988). These cognitive deficits
were observed in a wide range of neuropsychological tests, including orientation,
language, visuoconstructional ability, executive motor functions, and frontal lobe
tasks (Bolla-Wilson et al., 1989). In contrast, among patients with right-
hemisphere lesions, patients with major depression did not differ from nonde-
pressed patients on any of the measures of cognitive impairment. These findings
suggest that left-hemisphere lesions (particularly left frontal and left basal gan-
glia) associated with major depression may produce a different kind of depres-
sion than right-hemisphere lesions. Although there are several reports of im-
proved intellectual function in stroke patients treated with antidepressants (Fogel
& Sparadeo, 1985; Gonzalez-Torrecillas, Mendlewicz, & Lobo, 1995) these stud-
ies did not use double-blind controls.
It is difficult to confidently diagnose depression in a patient with severe com-
prehension deficits, and most investigators have excluded such patients from stud-
ies of post-stroke depression. Some investigators (Ross & Rush, 1981) have sug-
gested that a diagnosis of depression should be based on behavioral observations
Figure 10.3. Changes in ADL scores for depressed (major or minor) patients and non-
depressed patients at the time of the in-hospital evaluation and again 2 years later. De-
pressed patients show less recovery than nondepressed patients. (Reprinted with permis-
sion from Parikh et al., 1990.)
(i.e., diminished sleep and food intake, restlessness and agitation, and retarded
or tearful behavior). The reliability as well as sensitivity and specificity of these
criteria for detecting depression have not yet, however, been demonstrated.
Robinson and Benson (1981), in a study of depression in patients with fluent
or nonfluent aphasia, found that patients with nonfluent aphasia had a signifi-
cantly higher frequency of depression than did patients with fluent aphasia.
Although the higher frequency of depression among nonfluent aphasic patients
might be attributed to greater awareness of language impairment, we found that
the frequency of depression was no higher in aphasic patients than in nonapha-
sic patients and was variable, which accounted best for frequency of depression.
In their study, however, Starkstein and Robinson (1988) concluded that the most
important variable was lesion location. This finding suggests that nonfluent lan-
guage impairment and depression may not be causally related but may be inde-
pendent outcomes of the same lesion.
Robinson et al. (1983a) and Starkstein, Robinson, and Price (1987b) found among
patients with acute stroke that major depression was significantly associated with
lesions in anterior areas of the left hemisphere, including the left lateral frontal
cortex and the left basal ganglia (Fig. 10.4) (Starkstein et al., 1987a). Basal gan-
glia lesions (caudate and/or putamen) were associated with major depression in
seven of eight patients with left-sided lesions, while only one of seven patients
with right-sided lesions and none of the patients with left or right thalamic le-
sions had major depression. The association of acute left-hemisphere stroke with
major depression has also been reported by Astrom, Adolfsson, and Asplund
(1993) and Herrmann et al. (1995), but not by House et al. (1990a).
Among patients with right-hemisphere stroke, we found that those with frontal
or parietal damage showed the highest frequency of depression (Starkstein et al.,
Figure 10.4. The percentage of patients with major or minor depression, grouped ac-
cording to stroke lesion location. LC, left cortical; LS, left subcortical; RC, right cortical;
and RS, right subcortical. Patients with either left cortical or left subcortical lesions had
a significantly greater frequency of major depression during the acute stroke period than
patients with right hemisphere lesions. (Data from Starkstein et al., 1987b.)
Figure 10.5. Relationship between severity of depression and proximity of the CT

scan-visualized lesion to the frontal pole for patients with stroke or TBI involving the left
hemisphere. Lesions whose anterior border was closer to the frontal pole were associated
with more depressive symptoms. (Reprinted with permission from Robinson & Szetela,
1981.)
1989c). Similar results were reported by Finset (1988), who found that patients
with lesions in the right parietal white matter had a higher frequency of depression
than did patients with lesions involving other locations in the right hemisphere.
Perhaps the most consistent finding in post-stroke depression, however, has
been the association of depressive symptoms with intrahemispheric lesion loca-
tion. In 1981, we reported that among a group of 29 patients with left-hemisphere
lesions produced by trauma or stroke, there was an inverse correlation between
severity of depression and distance of the anterior border of the lesion from the
frontal pole as measured on CT scan (r = 0.76, P < 0.001) (Fig. 10.5) (Robin-
son & Szetela, 1981). In 1983, we reported the same phenomenon in another
group of 10 patients with single-stroke lesions of the left anterior hemisphere
(r = -0.92, P < .001). When patients with left posterior lesions were added (N =
18), the correlation decreased to r = —0.54, P < 0.05. This phenomenon was
also found in other groups of patients with purely cortical lesions of the left hemi-
sphere (N = 16; r = -0.52, P < 0.05) (Starkstein, Robinson, & Price, 1987b),
purely left subcortical lesions (N= 13; r = -0.68, P < 0.01) (Starkstein, Robin-
son, & Price, 1987b), and left-handed patients (Robinson et al., 1985). This phe-
nomenon has now been replicated by five different groups of investigators study-
ing patients from Canada (Eastwood et al., 1989; Sinyor et al., 1986), England
(House et al., 1990b), Germany (Herrmann, Bartles, & Wallesch, 1993), and Aus-
tralia (Morris et al., 1992a). Some found a correlation between severity of de-
pression and proximity of the lesion to the frontal pole in combined right- and
left-hemisphere lesion groups (House et al., 1990b; Sinyor et al., 1986), while
others found it only with left-sided lesions (Eastwood et al., 1989; Morris, Robin-
son, & Raphael, 1992a). Longitudinal studies have found that proximity of the
lesion to the frontal pole is significantly associated with severity of depression
most strongly during the first 6 months post-stroke (Astrom, Adolfsson, & As-
plund, 1993; Parikh et al., 1987), suggesting that the pathophysiology is a dy-
namic one that changes over time.
Although there is some difference in the strength of this correlation (and, there-
fore, the amount of variance in severity of depression explained by lesion loca-
tion), this phenomenon has emerged as one of the most consistent and robust
clinicopathological correlations ever described in neuropsychiatry. In summary,
several studies conducted by different investigators support the hypothesis that
major depressive disorder after acute stroke is more frequent following lesions
in the left anterior hemisphere than lesions at any other lesion location and that
depressive symptoms are more severe if the lesion is closer to the frontal pole.
Comparison of Cortical and Subcortical Lesions in the

Production of Post-Stroke Mood Disorders
Patients with CT-verified single-stroke lesions involving either cortical tissue or

restricted entirely to subcortical structures were examined for mood disorders
(Starkestein et al., 1987b). Those with left anterior lesions, either cortical or sub-
cortical, had significantly greater frequency and severity of depression than did
patients with any other lesion location. A strong correlation between the sever-
ity of the depression and the proximity of the lesion to the frontal pole was ob-
served for both left cortical and subcortical groups. Right-hemisphere lesions did
not show the same correlation with depression but were associated with a sig-
nificantly higher incidence of undue cheerfulness. These findings demonstrate
the importance of the location of subcortical lesions in post-stroke mood disor-
ders and suggest that anterior subcortical structures may play an important but
lateralized role in the production or regulation of mood.
Mechanism of Depression Following Stroke
Although the cause of post-stroke depression is not known, it has been hypoth-
esized that disruption of the biogenic amine-containing pathways by the stroke
lesion may play an etiological role (Robinson et al., 1983a). The noradrenergic
and serotonergic cell bodies are located in the brain stem and send ascending
projections through the medial forebrain bundle to the frontal cortex. The as-
cending axons then arc posteriorly and run longitudinally through the deep lay-
ers of the cortex, arborizing and sending terminal projections into the superficial
cortical layers (Morrison, Molliver, & Grzanna, 1979). Lesions that disrupt these
pathways in the frontal cortex or the basal ganglia may affect many downstream
fibers. Based on these neuroanatomical facts and on the clinical finding that the
severity of depression correlates with the proximity of the lesion to the frontal
pole, we have suggested that post-stroke depression may be the consequence of
severe depletion of norepinephrine, serotonin, or both produced by frontal or
basal ganglia lesions (Robinson et al., 1983a).
Supporting this hypothesis, some investigations have shown (in rats) that bio-
genie amines are depleted in response to ischemic lesions. This biochemical re-
sponse to ischemia is also lateralized (Robinson, 1979). Right-hemisphere lesions
produce depletions of norepinephrine and an accompanying behavior change of
locomotor hyperactivity, whereas lesions of the left hemisphere do not (Robin-
son, 1979).
Treatment of Depression Following Stroke
Although relatively few studies have examined the effectiveness of the treatment
of depression among patients with brain disease, there are three randomized,
double-blind studies of the efficacy of antidepressant treatment. Lipsey et al.
(1984) examined 14 patients treated with nortriptyline and 20 patients given
placebo. Patients received 25 mg for 1 week, 50 mg for 2 weeks, 75 mg for 1
week, and 100 mg for 2 weeks. The group taking the active drug (11 completed
the study) showed a significant decrease in depression scores compared with the
placebo group (15 completed the study) (Fig. 10.6). Side effects were observed
in 3 of 14 nortriptyline treated patients; two developed delirium, and one had
sudden syncope of unknown cause. Patients receiving nortriptyline showed a sig-
nificantly greater improvement in depression as measured by the Hamilton De-
pression Rating Scale and the Zung Self-Rating Depression Scale. Active and
placebo groups, however, did not differ significantly in their mean Hamilton De-
pression Scores until weeks 4 and 6 of treatment.
The second controlled study, carried out by Reding et al. (1986), demonstrated
the usefulness of another antidepressant drug (trazodone) for post-stroke de-
pression. In this study, 27 patients participating in a stroke rehabilitation pro-
gram were randomly assigned to treatment. Depressed patients taking trazodone
were found to have greater improvements in ADL scores than patients treated
with placebo. This trend became statistically significant when the treatment
groups were restricted to patients with abnormal dexamethasone tests.
The third treatment study was conducted by Andersen, Vestergaard, and Riis,
(1993), who used the specific serotonin-reuptake inhibitor (SSRI) citalopram.
Figure 10.6. Hamilton Depression scores during a 6 week double-blind treatment trial of
nortriptyline versus placebo for patients with depression (major or minor) after stroke. Pa-
tients receiving acute treatment improved significantly more than those receiving placebo.
(Reprinted with permission from Lipsey et al., 1984.)
The Hamilton Depression scores of stroke patients taking citalopram (N = 27)

were significantly more improved at both 3 and 6 weeks after beginning treat-
ment compared with those of patients taking placebo (N = 32).
In summary, although additional controlled treatment trials with a variety of
antidepressant medications need to be conducted, current data support the effi-
cacy of antidepressant medication, including the SSRIs, in the treatment of post-
stroke depression.
DEPRESSION ASSOCIATED WITH PARKINSON'S DISEASE
As with stroke, depression is a frequent finding in patients with Parkinson's dis-

ease (PD). Although the frequent association of emotional disorders with PD was
recognized more than 70 years ago (Lewy, 1923), it has only been within the
past several years that investigators have begun to empirically examine the na-
ture of the relationship. Some investigators have suggested that the high fre-
quency of depression in PD is the understandable consequence of progressive
physical impairment (Mindham, 1970). Other investigators have not, however,

found a significant correlation between the severity of depression and the sever-
ity of physical impairment and have suggested that depression may be a conse-
quence of neurochemical changes in specific brain areas (Mayeux, Stern, &
Williams, 1986; Mayeux, Williams, & Stern, 1984).
Prevalence
In several studies, the frequency of depression was reported to be around 40%

(Celesia & Wanamaker, 1972; Gothan, Brown, & Marsden, 1986; Mayeux,
Williams, & Stern, 1984). In a recent prospective study of a consecutive series
of 105 patients, Starkstein et al. (1990a) found that 21% met DSM-ffl criteria
for major depression, while 20% met DSM-III criteria for dysthymic (minor) de-
pression. The highest frequency of depression was found in the early and late
stages of PD (Fig. 10.7).
Figure 10.7. The percentage of patients (AT = 105) at each stage (I-V) of Parkinson's
disease who were depressed. All patients were attending an outpatient care clinic whose
disease ranged in duration from a few months to more than 15 years. The relative fre-
quency of depression was higher in both the early and late stages of the illness than in
the middle stages. We have hypothesized that the early depressions may be associated
with left-hemisphere dysfunction, whereas the late depression may be a psychological re-
sponse to impairment (Starkstein, Robinson, & Preziosi, 1990b). (Reprinted with per-
mission from Robinson & Travella, 1996.)
Relationship to Cognitive Impairment
In PD, cognitive impairments may range from subtle deficits in frontal lobe-
related tasks to an overt dementia (El-Awar, Bekcer, & Hammond, 1987). Mayeux,
Stern, and Rose (1981), using a modified Mini-Mental State Examination, reported
a significant correlation between cognitive deficits and severity of depression (i.e.,
severe depression was associated with severe cognitive impairments).
This relationship was also reported by Starkstein et al. in three studies. In the
first study, the association between depression, cognitive impairments, and stage
of PD was examined (Starkstein, Bolduc, & Preziosi, 1989a). Patients in the late
stages showed significantly greater overall cognitive impairments than did pa-
tients in the early stages, and those impairments were restricted to tasks involv-
ing motor-related functions (Fig. 10.8). Depressed patients in the late stages of
the disease showed the most significant impairment (Starkstein et al., 1989b).
Taken together, these findings suggest that cognitive deficits may primarily be a
result of motor impairments, but, when depression also occurs, the cognitive
deficits are greater and increase in severity as the PD progresses (Starkstein,
Bolduc, & Preziosi, 1989a).
Figure 10.8. Cognitive performance as measured by the number of correctly selected cat-
egories on the Wisconsin Card Sorting Task and seconds to complete the Trail Making
Test by Parkinson's disease patients with and without depression. Depressed patients were
significantly (P < 0.05) more impaired than nondepressed patients during the moderate
and severe stages of PD. Among the depressed patients, performance on these "frontal
lobe" tasks declined with advancing stages of PD. (Reprinted with permission from Robin-
son & Travella, 1996.)
In the second study, the association between cognitive impairments and type of
severity of depression (major or minor) among patients with PD was examined.
No differences were found on cognitive tasks between minor depressed and non-
depressed patients, but patients with major depression showed the worst cognitive
performance. This impairment was greatest on frontal lobe-related tasks, such as
the Wisconsin Card Sorting test (Starkstein et al., 1989b). In the third study, the
influence of depression on the longitudinal evolution of cognitive deficits was ex-
amined in a 3-4 year follow-up. Both groups, depressed and nondepressed patients,
showed significant declines in Mini-Mental State Examination scores over time,
but the depressed patients had significantly greater cognitive decline than did non-
depressed subjects (Starkstein, Bolduc, & Preziosi, 1989a).
These findings demonstrate that depression may be associated not only with
cognitive impairments at the time depression is present but also with more rapid
cognitive deterioration. These findings support the speculation of Sano, Stern,
and William (1989) that depression may be an early finding in patients with PD
who later show dementia.
Mechanism
Several studies have demonstrated that patients with PD and dementia may show
senile plaques and neurofibrillary tangles compatible with the diagnosis of
Alzheimer's disease (AD) as well as severe depletion of cholinergic neurons in
the nucleus basalis of Meynert or Lewy bodies in cortical regions (Perry, Cur-
tis, & Dick, 1985). Few neuropathological studies have, however, been carried
out in patients with PD and depression. Depression in PD may also be related
to changes in other biogenic amines. Mayeux, Williams, and Stern (1984)
showed that patients with PD and depression had significantly lower 5-HIAA
(a metabolite of serotonin) levels in the cerebrospinal fluid than did patients
with PD without depression. However, patients with PD and both dementia and
depression had the lowest 5-HIAA cerebrospinal fluid values (Sano, Stern, &
William, 1989).
In a recent study, the metabolic abnormalities associated with depression in
PD were examined with neuroimaging techniques (Mayberg et al., 1990). Re-
gional cerebral glucose metabolism was determined in depressed (TV = 5) and
nondepressed (N = 4) patients with PD using [18F]-fluoro-l-deoxy-D-glucose
(FDG) PET. Patients with PD and major depression had significantly lower meta-
bolic activities in the head of the caudate and the inferior frontal cortex than did
nondepressed PD patients of comparable age, duration, and stage of illness. More-
over, there was a significant correlation between Hamilton Depression Scale
scores and the relative regional metabolism in the inferior frontal cortex (r =
0.73, P < 0.05) (i.e., the lower the relative regional metabolic activity in the in-
ferior frontal cortex, the more severe the depression).
Treatment
A question that remains unanswered is whether the treatment of depression may

influence the progression of intellectual impairments in patients with PD. In the
longitudinal 3-4 year follow-up study (Starkstein et al., 1990a), six patients in
the depressed group who had received treatment for depression had only an 11%
decrease in cognitive scores compared with a 23% decrement in cognitive scores
among non-treated depressed patients. Moreover, the two patients who were re-
ceiving the highest doses of tricyclics did not show a decline in their Mini-
Mental State Examination scores. These preliminary findings are very encour-
aging, and further prospective double-blind treatment studies are needed to de-
termine whether the use of antidepressants may delay the progression of cogni-
tive impairment in patients with PD.
DEPRESSION ASSOCIATED WITH TRAUMATIC BRAIN INJURY
Kinsella, Moran, and Ford (1988) reported that, in a series of 39 patients, 33%
were classified as depressed and 26% as suffering from anxiety within 2 years
of severe head injury. Fedoroff et al. (1992) and Jorge et al. (1993b) found that
28 of 66 patients (42%) admitted to a head trauma unit developed major de-
pression at some point during a 1-year follow-up period. Of 66 patients admit-
ted to the hospital with acute closed head injury without significant spinal cord
or other organ system injury, 17 (26%) met diagnostic criteria for major depres-
sion at the time of the initial in-hospital evaluation. In addition, 3% met criteria
for minor (dysthymic) depressive disorder. This frequency is consistent with that
found by several other investigators (Brooks, Campsie, & Symington, 1986;
Gualtieri & Cox, 1991).
Longitudinal Course of Depression
Mood disorders following TBI may be transient syndromes lasting for a few
weeks, or they may be persistent disorders lasting for many months (Grant & Al-
wes, 1987). Other authors have suggested that transient disorders may be the re-
sult of neurochemical changes provoked by brain injury, whereas prolonged de-
pressive disorders may be of a more complex nature and may be reactive to
physical or cognitive impairment (Lishman, 1988; Prigatano, 1987; VanZomeren
& Saan, 1990).
We have reported empirical data to support these suggestions (Jorge et al.,
1993b). Diagnoses of depression were based on a semistructured psychiatric in-
terview (Wing, Cooper, & Sartorius, 1974). Of the original 66 patients evaluated
with acute TBI, 54 were re-evaluated at 3 months, 43 at 6 months, and 43 at 1
year. The prevalence of depression was 30% at 3 months, 26% at 6 months, and
26% at 1 year (Jorge et al., 1993a). The mean duration of major depression was 4.7
months. There was, however, a group of seven patients (41 % of the depressed group)
who had transient depressions lasting 1.5 months, while the nine remaining patients'
depression had a mean duration of 7 months. The patients with transient depression
showed a strong association with left anterior lesion location (Fischer exact P =
0.006). Prolonged depressions, on the other hand, were associated with impaired so-
cial functioning, suggesting that biological factors may lead to transient depression,
whereas prolonged depressions may result from psychological factors.
Risk Factors for Depression Following Traumatic Brain Injury
Several premorbid factors may influence patients' emotional responses to acute

TBI and may, therefore, be relevant to the etiology of depressive disorder fol-
lowing TBI (Lishman, 1973). In the study of 66 patients with acute TBI, there
was a significantly greater frequency of previous personal history of psychiatric
disorder in the major depressed group than in the nondepressed patients (Fedo-
roff et al., 1992). In addition, the depressed patients had significantly more im-
paired social functioning as measured by the Social Functioning Examination
(SFE) (Starr, Robinson, & Price, 1983) (Fig. 10.9). The SFE, during the initial
Figure 10.9. Social functioning exam (SFE) scores for patients either with major de-
pression or without depression during 1 year after traumatic brain injury (TBI). The SFE
scores reflect function during the month before evaluation. Therefore, the initial score in-
dicates social functioning before TBI. Both before and after head injury, patients with de-
pression had significantly more impaired social functioning than nondepressed patients.
This probably reflects the effect of depression on social functioning and vice versa.
(Reprinted with permission from Robinson & Travella, 1996.)
evaluation, measured the quality and personal satisfaction with social function-
ing during the period before brain injury. This suggests, as other investigators
have reported, that patients with poor social adjustment and social dissatisfac-
tion before the brain injury were more prone to develop depression.
Some empirical evidence supports an association between post-TBI depression

and specific lesion locations. Lishman (1968) reported that several years after
penetrating brain injury, depressive symptoms were more common among pa-
tients with right-hemisphere lesions. Depressive symptoms were also more fre-
quent among patients with frontal and parietal lesions than among those with le-
sions at other locations. Grafman, Vance, and Swingartner (1986) also reported
that, several years after head injury, depressive symptoms were more frequently
associated with penetrating injuries involving right-hemisphere (right or-
bitofrontal) lesions than lesions at other locations.
Traumatic brain injury is characterized by the presence of diffuse and focal
lesions that may be the direct result of traumatic shear injury or secondary to
ischemic complications (Katz, 1992). Of the 66 patients previous described, 42
(64%) had a diffuse pattern of brain injury on their CT scans, and 24 (36%) pre-
sented with focal lesions. There were no significant differences between major
depressed and nondepressed groups in the frequencies of diffuse or focal patterns
of injury. In addition, no significant differences were found in the frequencies of
extraparenchymal hemorrhages, contusions, intracerebral or intraventricular hem-
orrhages, hydrocephalus, or CT findings suggestive of brain atrophy. There was,
however, a significant association between lesion location and the development
of major depression. The presence of left anterior hemisphere lesions (i.e., left
dorsolateral frontal cortex or left basal ganglia) was the strongest correlate of
major depression (Fig. 10.10). In contrast, other frontal lesions (i.e., left, right,
or bilateral frontal lesions, including orbitofrontal cortex) were associated with
a lesser probability of development of major depression (Fedoroff et al., 1992).
These results are consistent with previous findings in stroke patients of an in-
creased frequency of depression among patients with left dorsolateral cortical
and left basal ganglia lesions (Starkstein, Robinson, & Price, 1987b).
Relationship to Impairment Variables
Empirical studies have reported conflicting findings with regard to the relation-
ship between impairment and depressive symptoms following TBI (Bornstein,
Miller, & VanSchoor, 1989; Prigatano, 1986). In the previously described study
of 66 patients with TBI, there was no significant association between depression
and severity of intellectual impairment (i.e., Mini-Mental State Examination) or
Figure 10.10. The proportion of patients with major depression or no mood disturbance
at 1 month after traumatic brain injury (TBI) who had evidence on CT scan of injury in-
volving the left dorsal lateral frontal cortex and/or left basal ganglia. Because patients
with TBI frequently have multiple areas of injury, a logistic regression analysis was used
to examine the independent effects of each area of injury. The strongest independent ef-
fect of lesions on depression was found in this left anterior brain region. (Reprinted with
permission from Robinson & Travella, 1996.)
ADL (Fedoroff et al., 1992). Social functioning, however, was the clinical vari-
able that had the most consistent relationship with depression throughout the
follow-up period (Jorge et al., 1993b). One might infer from these findings that
social intervention as well as the treatment of depression may be necessary to al-
leviate these severe and long-lasting mood disorders.
Treatment
There have been no double-blind, placebo-controlled studies of the efficacy of

pharmacological treatments of depression in TBI patients. The selection of anti-
depressant drugs for the treatment of post-TBI depression is usually guided by

their side-effect profiles. Mild anticholinergic activity, minimal lowering of
seizure threshold, and low sedative effect are the most important factors to be
considered in the choice of an antidepressant drug for this population (Silver,
Hales, & Yudofsky, 1990).
There are case reports of successful treatments of post-TBI depression with
psychostimulants (Gualtieri, 1988). These include dextroamphetamine (8-60
mg/day), methylphenidate (10-60 mg/day), and pemoline (56-75 mg/day). They
are prescribed twice a day, with the last dose at least 6 hours before sleep to pre-
vent initial insomnia. Treatment is begun at lower doses, which are then gradu-
ally increased. Patients taking stimulants need close medical monitoring to pre-
vent abuse or toxic effects.
Electroconvulsive therapy is not contraindicated in TBI patients. It may be
considered when other methods of treatment are unsuccessful.
Finally, the role of social interventions and adequate psychotherapeutic support
should be considered in the treatment of depression. Psychological and pharma-
cological treatments, however, need to be examined in controlled treatment trials.
Emotional and mood disorders are commonly associated with brain injury. In-
sights into the causes of these disorders may be gained by investigation of their
similarities and differences in several different neurological disorders. This chap-
ter has focused on mood disorders associated with stroke, PD, and TBI.
There are numerous emotional and behavioral disorders that occur after cere-
brovascular lesions. Mania is a rare complication of stroke and is strongly asso-
ciated with right-hemisphere damage involving the orbitofrontal cortex, basal
temporal cortex, thalamus, or basal ganglia. Risk factors for mania include a fam-
ily history of psychiatric disorders and subcortical atrophy. Although patients
with secondary mania are usually treated with medications with proven efficacy
in primary mania, the most effective treatment modality remains to be deter-
mined. Bipolar disorders are associated with subcortical lesions of the right hemi-
sphere, whereas right cortical lesions lead to mania without depression. Depres-
sion occurs in about 40% of stroke patients. Depression is significantly associated
with left frontal and left basal ganglia lesions during the acute post-stroke period
and may be successfully treated with nortriptyline.
Major depression and dysthymic disorders are frequent in PD. Depression may
be associated not only with cognitive impairments at the time depression is pres-
ent but also with more rapid cognitive deterioration. Further studies are needed
to determine whether the use of antidepressants may delay the progression of
cognitive impairment in patients with PD.
Among patients with acute TBI, 25% of those studied fulfilled criteria for ma-
jor depressive disorders. The mean duration of major depression was 4.7 months,
and a total of 42% developed major depression at some time during the first year
after injury. Patients with generalized anxiety disorder and comorbid major de-
pression had longer lasting mood problems than did patients with depression and
no anxiety.
There are many areas that are ripe for future research. The most important el-
ements of social functioning that contribute to depression need to be explored,
as well as the effect of social intervention. The role of antidepressants in treat-
ing these depressive disorders has not been systemically explored and deserves
study.
Finally, the mechanism of these depressions, both those associated with psy-
chosocial factors and those associated with neurobiological factors (e.g., strate-
gic lesion locations), need to be investigated. It is only through the discovery of
their mechanism that specific and rational treatment strategies for these disorders
will be developed.
ACKNOWLEDGMENTS
The authors are indebted to Drs. Sergio E. Starkstein, Thomas R. Price, John R. Lipsey, Rajesh M.
Parikh, J. Paul Fedoroff, Helen S. Mayberg, and Karen Bolla, who participated in many of these
studies. This work was supported by the following NIMH grants: Research Scientist Award MH00163,
MH52879, and MH53592.
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II
Regional Brain Function in
Sadness and Depression
RICHARD J. DAVIDSON AND

JEFFREY HENRIQUES
Over the last 15, years there has been increased interest in the cerebral lateral-
ization of emotion and emotion-related psychopathology (e.g., Davidson &
Tomarken, 1989). Although numerous studies point to right-hemisphere special-
ization in the perception of emotional information (see Silberman & Weingart-
ner, 1986), evidence suggests that the anterior regions of the right and left hemi-
spheres play different roles with respect to the production of emotion. Following
from Schneirla's argument (1959) that approach and withdrawal underlie all mo-
tivated behaviors across phylogeny, Davidson and others (i.e., Davidson, 1984,
1987, 1992, 1995; Davidson & Tomarken, 1989; Kinsbourne, 1978) have pro-
posed that the anterior regions of the left and right hemispheres are specialized
for approach and withdrawal behavior, respectively. For instance, the induction
of a withdrawal-related emotion, such as disgust, has been shown to be associ-
ated with an increase in relative right-sided anterior activation, while increased
relative left-sided activation accompanies approach-related emotions such as hap-
piness (e.g., Davidson et al., 1990b; Fox & Davidson, 1986). Gray (1994) pro-
posed similiar conceptual systems with a different functional anatomy and has
labeled these systems the Behavioral Approach System (BAS) and the Behav-
ioral Inhibition System (BIS).
At the same time, factor analytic studies of mood have identified two broad
orthogonal factors: positive affect (PA) and negative affect (NA), (Tellegen,
269
1985; Watson & Tellegen, 1985). These two factors appear to tap behavior re-
flective of approach and withdrawal. NA is described generally as subjective
distress and includes mood states such as fear, disgust, and anxiety (Watson,
Clark, & Carey, 1988), prototypical withdrawal-related emotions (Davidson &
Tomarken, 1989). PA does not reflect happiness per se, but rather "one's level
of pleasurable engagement with the environment" (Watson, Clark, & Carey, 1988,
p. 347). High PA is characterized by enthusiasm, mental alertness, and determi-
nation, while low PA is characterized by lethargy and fatigue. Studies using these
affect dimensions have shown that it is the loss of PA that differentiates depres-
sion from other negative affect states such as anxiety (Bouman & Luteijn, 1986;
MacLeod, Byrne, & Valentine, 1996; Watson, Clark, & Carey, 1988).
Although investigations of experimentally induced affect demonstrate con-
sistent changes in frontal asymmetry across subjects between approach- and
withdrawal-related emotion conditions (i.e., Davidson et al., 1990b), these
changes in relative asymmetry are superimposed on considerable individual vari-
ation in absolute asymmetry. These asymmetries in absolute anterior activation
are predicted to reflect affective style and to affect an individual's vulnerability
to particular types of psychopathology (Davidson, 1998). In line with this, stud-
ies have shown that individuals with relative left-sided frontal activation are char-
acterized by high levels of PA and self-reported activity in the BAS (e.g., Har-
mon-Jones & Allen, 1997; Jacobs & Snyder, 1996; Sutton & Davidson, 1997;
Tomarken et al., 1992). Subjects with relative right-sided frontal activation are
characterized by high levels of NA and self-reported activity in the BIS (Sutton
& Davidson, 1997; Tomarken et al., 1992). Within this model, absolute anterior
asymmetry by itself does not produce a particular pattern of emotional behavior
or psychopathology; instead, anterior asymmetry is seen as a diathesis for the ex-
pression of emotional behavior, given an appropriate affect elicitor. For instance,
individuals with increased relative right anterior activation report more NA in re-
sponse to emotion-eliciting film clips than do subjects with relatively more left
anterior activation (Tomarken, Davidson, & Henriques, 1990; Wheeler, David-
son, & Tomarken, 1993).
Within the context of this model, sadness and depression which are associated
with decreased PA, should be associated with decreased left frontal activation, and
individuals who are characterized by a relatively stable pattern of left anterior hy-
poactivation should be more susceptible to the elicitation of sad mood and at in-
creased risk for depression. Note that this model is only proposing a relation be-
tween left anterior function and sad mood and depression, not one involving the
relative pattern of activation between the two hemispheres. Variations in right an-
terior function should reflect variations in NA among individuals. Thus, depressed
individuals who have increased right frontal activity would be expected to be at
risk for withdrawal-related emotions as well and would typically present a clinical
picture of a depressed and anxious mood. Individuals who have concurrent low
Regional Brain Function in Sadness and Depression 271
right frontal activation should be less susceptible to withdrawal-related emotions,

as well as to approach-related emotions, and would typically present a clinical pic-
ture of depressed flattened affect. This variability in predicted symptom profile mir-
rors the clinical literature (e.g., Baumeister, 1990; Roth et al., 1972).
The evidence for decreased left anterior activation in depression has grown
slowly, and the results of studies that have examined patterns of cerebral acti-
vation during the elicitation of sadness seem to suggest different conclusions.
One of the assumptions that appears to underlie work in this area is that sadness
and depression are on the same continuum and that the differences are merely
one of degree. That assumption may not, however, be correct. Sadness is only a
part of depression, and it may be that the other symptoms, such as loss of inter-
est, loss of pleasure, and social withdrawal, play a much larger role in the dif-
ferences in regional brain activation that have been observed between depressed
and nondepressed subjects.
STUDIES OF CEREBRAL INACTIVATION AND LESIONS
Investigators who have used sodium amytal to selectively anesthetize a cerebral

hemisphere have found that inactivation of the left hemisphere produces a dys-
phoric reaction in some subjects, while inactivation of the right hemisphere is
associated with euphoria or indifference (e.g., Alema & Rosadini, 1964; Chris-
tianson et al., 1993; Lee et al., 1990; Terzian, 1964). Although some authors
(e.g., Flor-Henry, 1979) have interpreted these data in the context of a right-
hemisphere role for sadness and depression, it should be noted that the dysphoric
reaction described does not occur immediately after the left hemisphere has been
anesthetized but emerges as the hemisphere resumes functioning and the lan-
guage disturbances and hemiplegia resolve (Terzian, 1964). This suggests that
the dysphoric reaction observed following left-hemisphere barbiturization is not
necessarily the result of a disinhibited right hemisphere but rather could result
from decreased activation in the left hemisphere. Additionally, lesion studies have
shown that increased tearfulness and crying were associated with left-sided le-
sions (e.g., Gainotti, 1972; House et al., 1989; Sackeim et al., 1982). Thus, in
these studies, sad mood is associated with left-sided inactivation.
A number of investigators who have studied mood disturbances in epileptics
have found that patients with left-sided epileptogenic lesions report significantly
higher levels of depression than do patients with right-sided lesions during the in-
terictal period (e.g., Altshuler et al., 1990; Bear & Fedio, 1977; Black, 1975; Gas-
parrini et al., 1978; Mendez et al., 1994; Perini, 1986; Perini & Mendius, 1984).
Given that the region of epileptic focus is usually characterized by hypometabo-
lism during the interictal period (Engel, 1984), these studies are consistent with
the idea of an association between left anterior hypoactivation and depression.
For the most part, these studies have not addressed the issue of the ante-
rior/posterior dimension within the hemisphere, an important issue given the dif-
ferential role these regions play in behavior (see Davidson, 1992). Robinson and
coworkers have systematically and elegantly investigated the nature of post-stroke
mood disturbance (e.g., Lipsey et al., 1983; Robinson et al., 1984, 1985; Robin-
son & Szetela, 1981; Starkstein, Robinson, & Price, 1987). They have used com-
puterized tomography scans to precisely specify lesion location and have used
standardized diagnostic interviews to characterize the nature of the emotional dis-
turbance. They have found that the severity of post-stroke depression was posi-
tively related to the lesion's proximity to the frontal pole in the left hemisphere
such that more anterior lesions were associated with increased depression (Lipsey
et al., 1983; Robinson et al., 1984). Investigation of right-hemisphere damage
and depression point to an inverse relation such that more posterior lesions were
associated with increased severity of depression (Robinson et al., 1984).
The depression observed in these patients is phenomenologically similar to
clinical depression (Lipsey et al., 1986), and comparisons of depressed patients
with and without stroke-induced lesions reveal that both groups have similar lev-
els of depression. The only difference between groups is the greater cognitive
and physical impairment observed in post-stroke depressed patients relative to
neurologically intact depressed patients (Lipsey et al., 1986). Given this differ-
ence in cognitive function, it should be noted that the severity of post-stroke de-
pression has not been found to be related to the severity of the functional im-
pairment produced by the stroke; rather, it is lesion location that appears to be
the critical variable (Robinson & Price, 1982).
Although one study has replicated Robinson's work (Sinyor et al., 1986), a
second study has not found an increased incidence of major depression among
subjects with left-hemisphere lesions (House et al., 1990). Gainotti (1989) has
argued that because not all subjects with left anterior lesions become depressed
the hypothesis of a relation between left frontal inactivation and depression should
be rejected. His view is predicated on the idea that left frontal lesions are suffi-
cient to produce depression. Davidson (1993) has offered an alternative frame-
work for understanding this corpus of evidence based on a diathesis-stress model.
While subjects with left anterior lesions are presumed to be at increased risk for
depression, the fact that not all of these subjects become depressed merely demon-
strates that decreased left anterior activation is not sufficient for the occurrence
of depression. It is quite possible that the House et al. (1990) subjects, while hav-
ing the diathesis, simply had not had a sufficient level of stress to elicit a de-
pressive episode. In fact, there were differences between the patient samples stud-
ied by House and Robinson: Fewer than half of the subjects in the House et al.
(1990) study had been hospitalized as a result of their stroke, and less than one-
third lived alone. In contrast, only one third of the subjects examined by Robin-
son and Price (1982) were married, and all had been hospitalized for their strokes.
The findings from this literature appear to be generally supportive of the idea
that decreases in left-sided activation, specifically in the anterior cortical zones, are
associated with sadness and depression. None of the studies reviewed thus far has,
however, provided a concurrent assessment of cerebral function. Thus, these find-
ings do not rule out the possibility that the observed changes in mood are the re-
sult of changes elsewhere in the brain. To that end, it is necessary to investigate
cerebral functioning in an anatomically intact population. This question has been
addressed with both electrophysiological and radioactive ligand studies.
ELECTROENCEPHALOGRAM STUDIES
Methodological Issues
Interpretation of the growing corpus of work utilizing electroencephalography

(EEG) can be difficult for a number of reasons, including the use of different pa-
rameters, variability in the sites from which data were recorded, and variability
in the frequency bands analyzed. Furthermore, there are some studies that can-
not be interpreted because of methodological flaws, including failure to control
for type I error, failure to transform raw EEG, and failure to remove muscle and
eye movement artifact. Raw values of relative and absolute power are not nor-
mally distributed (Gasser, Bacher, & Mocks, 1982). In fact, "[t]hese deviations
[from normality] are usually rather gross" (Gasser et al., 1982, p. 119), and this
poses problems for the use of parametric statistics. Gasser, Bacher, and Mocks
(1982) examined several different methods of data transformation and found that
a log transformation of absolute power resulted in the best approximation of a
normal distribution. Relative power more closely approximated a normal distri-
bution before transformation, and using a log(x/l — x) transform resulted in an
almost perfect normal distribution. Some investigators do not remove epochs con-
taminated by muscle artifact either in the assumption that electromyographic
(EMG) activity is symmetrical or in the belief that the filtering of all signals
above 30 Hz removes EMG activity. Evidence suggests that EMG activity is not
symmetrical (Volavka et al., 1981), and EMG power can be detected in bands
as low as 10 Hz (see Davidson, 1988). This makes it difficult to interpret the re-
sults of studies that do not remove EMG artifact, especially those recording from
the temporal regions, which are particularly susceptible to muscle artifact (e.g.,
Flor-Henry et al., 1979; Ulrich et al., 1984).
The EEG measures used by investigators fall into two broad categories: mea-
sures of amount (e.g., relative power) and measures of variability (e.g., coeffi-
cient of variation). Investigators use these measures to examine activity in broad
frequency, bands (e.g., 0.5-30 Hz) or in specific frequency bands (e.g., delta [1-4-
Hz], theta [4-8 Hz], alpha [8-13 Hz], beta 1 [13-20 Hz]). Although studies vary
with regard to the specific frequency bands examined, almost all assess activity
in the alpha band (e.g., Henriques & Davidson, 1990, 1991; Matousek, Capone,
& Okawa, 1981; Ferris et al., 1981). Power in the alpha band is inversely cor-
related with relative brain activation, with a decrease in alpha power indicative
of an increase in brain activation (Lindsley & Wicke, 1974). Davidson et al.
(1990a) examined patterns of activation during performance of spatial and ver-
bal tasks and found that greater power suppression occurred in all bands, in the
hemisphere putatively most activated. This suggests that increased activation is
associated with decreases in power across bands. It is less clear what differences
in variability reflect. For the most part, increases in variability have been inter-
preted as reflecting increases in activity, based on the assumption that cortical
activation would be associated with neuronal desynchrony and thus increased
variability in the EEG. Flor-Henry et al. (1979) examined both power and vari-
ability and reported decreases in variability coincident with increases in power.
Studies of Induced Sadness
In one of the earliest studies of induced sadness, Tucker et al. (1981) recorded
the EEG activity from across the head during the induction of depression and eu-
phoria. Differences between the two mood states were only observed in the frontal
regions. Relative to the euphoric mood state, depressed mood was associated with
more left and less right alpha power, indicating that depression was associated
with relative right-sided activation. Ahern and Schwartz (1985) investigated EEG
asymmetry in response to questions designed to elicit happy, excited, neutral,
sad, or fearful responses. This study did not report data from the individual hemi-
spheres and did not include any assessment of whether these differential moods
had been induced. Their asymmetry data showed no difference in frontal alpha
asymmetry between happiness and sadness. Both of these emotion conditions had
relatively more left-sided activation than did the other three emotion conditions
studied. Given the contradictory results found thus far, it is clear that more stud-
ies are needed to examine the relations between patterns of EEG activation and
induced sad mood in normal individuals. One of the critical problems in this
work is the need to verify that the intended emotion was indeed induced. Ide-
ally, measures other than simple self-report should be used because there are
strong expectancy effects in studies that use mood induction. Measures of spon-
taneous facial behavior can be fruitfully used as an unobtrusive index of the in-
duced emotion (e.g., Davidson et al., 1990b).
Studies of Depression
Most EEG studies of depression have compared depressed and nondepressed sub-
jects' resting patterns of brain electrical activity. Unfortunately, not all studies
have included frontal measures (e.g., Cazard, 1989; Cazard, Ricard, & Facchetti,
1992; Ulrich et al., 1984). Henriques and Davidson (1991) examined the activ-
ity in four different frequency bands at six scalp sites in each hemisphere in a
group of clinically depressed individuals. The one region where depressed sub-
jects differed from normal controls was in the midfrontal region and involved
the patterning of alpha power. Depressed subjects had relative right-sided frontal
activation as a result of hypoactivation in the left hemisphere.
These findings mirror earlier work with subclinically depressed people (Schaf-
fer, Davidson, & Saron, 1983). Because there is not a clear consensus in the lit-
erature regarding referencing strategies (see Davidson, 1988; Lehman, 1987;
Nunez, 1981), data were derived with three different reference montages, and the
pattern of left frontal hypoactivation was consistent across montages. We have
also found this pattern of left frontal hypoactivation in remitted depressed pa-
tients (Henriques & Davidson, 1990). A recent study replicated these results,
finding that both currently depressed and previously depressed subjects had less
left frontal activation than never depressed controls (Gotlib, Ranganath, & Rosen-
feld, 1998). Similar findings have been reported in a small group of bipolar sub-
jects with seasonal affective disorder (Allen et al., 1993). Another study that ex-
amined the stability of frontal asymmetry in a group of 25 depressed subjects
over an 8 week period found that changes in symptom severity were unrelated
to frontal asymmetry (Hitt, Allen, & Duke, 1995). Furthermore, the intraclass
correlations between the two testing occasions ranged from 0.51 to 0.81. All of
these findings point to a trait-like role for decreased left frontal activation in de-
pression, supporting the view that left hypoactivation serves as a diathesis for
the experience of depression.
While studies have reported differences in posterior asymmetry, these findings
have been mixed (e.g., Henriques & Davidson, 1990; von Knorring, 1983). d'Elia
and Perris (1973, 1974) found decreases in left posterior variability among de-
pressed subjects, and this variability increased on recovery. In contrast, von Knor-
ring (1983) found that depressed subjects had more variability in the right hemi-
sphere than did controls. Increased right posterior activation (decreased relative
alpha power) has been reported by Pozzi et al. (1995) and Suzuki et al. (1996).
Other studies suggest that depression is associated with decreased right posterior
activation. Cazard (1989) recorded from the parietal regions and found that de-
pressed subjects had less variability in the right than left hemisphere, while con-
trols had similar variability in the two hemispheres. Recovery was associated
with an increase in variability in both hemispheres and the loss of any asymme-
try. A subsequent study found decreased right posterior variability in all depressed
subjects, while only the most severe cases also had decreased left posterior vari-
ability (Cazard, Ricard, & Facchetti, 1992). We have found decreased right pos-
terior activation in remitted depressed patients (Henriques & Davidson, 1990),
but not in currently depressed subjects (Henriques & Davidson, 1991).
All of the aforementioned studies have examined subjects during resting con-
ditions. A more consistent pattern of decreased right posterior activation in de-
pression emerges when subjects are compared during cognitive task performance,
and these results are consistent with those from behavioral studies that depressed
subjects have a selective impairment in spatial task performance (e.g., Miller et
al., 1995). We compared depressed and nondepressed subjects on psychometri-
cally matched verbal and spatial tasks and found that depressed subjects per-
formed worse than controls on the spatial task but performed similar to controls
on the verbal task (Henriques & Davidson, 1997). EEGs recorded during these
tasks showed that depressed subjects showed no increase in activation in the right
posterior regions during spatial task performance. Control subjects, in contrast,
had a pattern of relative right-sided activation during the spatial task and rela-
tive left-sided activation during the verbal task. Using the same tasks, Reid, Allen,
and Duke (1995) had similar results. In a study examining patterns of EEG ac-
tivation in response to lateralized facial stimuli, Davidson, Schaffer, and Saron
(1985) found that depressed subjects had an inverse relationship between frontal
and parietal asymmetries that was not seen in control subjects. Among depressed
subjects, larger decreases in left frontal activation were associated with greater
decreases in right parietal activation.
In work examining EEG patterns of activation in elderly depressed subjects,
the pattern observed is one of a global decrease in activation compared with non-
depressed subjects (Pollock & Schneider, 1990). This pattern of increased alpha
power across the head also characterizes recovered elderly depressed people (Pol-
lock & Schneider, 1989). Global decreases in activation have also been found by
Roemer et al. (1992), who additionally found greater left-sided power in the theta,
alpha, and beta bands among depressed subjects.
Although there has not been enough work done on EEG changes associated
with sadness to draw any firm conclusions (Ahern & Schwartz, 1985; Tucker et
al., 1981), depression appears to be associated with decreased left-sided anterior
EEG activation (e.g., Allen et al., 1991; Gotlib, Ranganath, & Rosenfeld, 1998;
Henriques & Davidson, 1990, 1991; Schaffer, Davidson, & Saron, 1983). The
patterning of posterior asymmetry in depression is less clear. Findings include
left-sided decreases in activation (e.g., d'Elia & Penis, 1973, 1974), right-sided
increases (von Knorring, 1983), right-sided decreases (e.g., Allen et al., 1991;
Cazard, 1989; Henriques & Davidson, 1990), and bilateral decreases (Pollock &
Schneider, 1989, 1990). Heller and associates (1997) have suggested that differ-
ences in posterior asymmetry reflect differences in anxious arousal such that
right-sided activation reflects the somatic arousal and tension associated with
anxious arousal whereas left-sided activation is associated with the worry and
verbal rumination of anxious apprehension. In fact, a recent study comparing
anxious and nonanxious depressed subjects found that those who were nonanx-
ious were characterized by decreased activation over the right parietotemporal
sites and those who were anxious had increased right posterior activation (Bruder
et al., 1997). Relations between increased right posterior activation and increased
anxiety in depression has also been reported by Matousek (1991).
EVOKED POTENTIAL STUDIES
In evoked potential studies, when subjects are required to make a discrimination

between a target and a nontarget stimulus, there is an identifiable positive peak
occurring at about 300 msec post-stimulus (P300). The classic P300 waveform
has a posterior distribution and has been hypothesized as reflecting an updating
in memory of the stimulus representation (Coles, Gratton, & Fabiani, 1990). Its
elicitation reflects, among other things, the psychological value or meaning of
the stimulus and the relative probability of the stimulus' occurrence. The com-
ponents of the evoked potential waveform that occur within the first 250 msec
of stimulus onset are believed to be associated with early sensory and attentional
processes (Naatanen & Picton, 1987). To the best of our knowledge, there are
no studies that have examined event-related potentials (ERPs) during the elici-
tation of sadness.
Studies of Depression
There is a considerably larger corpus of work with ERP studies of depression than
with EEG studies of depression (for reviews, see Henriques & Davidson, 1989;
Zahn, 1986); however, relatively few have examined the issue of asymmetry and
depression (e.g., Bruder et al., 1995; Tenke et al., 1993). In studies that have not
examined asymmetry, some have not found differences between depressed and
nondepressed subjects in P3 amplitude (e.g., Giedke, Thier, & Bolz, 1981) or in
latency (e.g., Giedke, Thier, & Bolz, 1981; Kraiuhin et al., 1990; Pfefferbaum et
al., 1984). Other investigators have reported that depressed subjects have decreased
P3 amplitudes compared with controls (e.g., Diner, Holcomb, & Dykman, 1985;
Pfefferbaum et al., 1984; Thier, Axmann, & Giedke, 1986). The results of exam-
inations of other components of the evoked potential waveform are also mixed,
with some investigators reporting increased amplitudes among depressed subjects
(e.g., Elton, 1984; Khanna, Mukundan, & Channabasavanna, 1989; Vasile et al.,
1989), others reporting no differences (e.g., Diner, Halcomb, & Dykman, 1985;
Knott et al., 1991; Plooij-van Gorsel, 1984; Thier, Axmann, & Giedke, 1986), and
still others reporting decreases (e.g., Giedke, Thier, Bolz, 1981; Roth et al., 1981).
Bruder (1992) has suggested that the use of overly simple tasks has resulted in
the failure to find consistent differences between depressed and nondepressed sub-
jects. Similar reasoning may explain why the EEG literature, reviewed above, re-
ports variability in resting posterior differences yet consistent right posterior de-
creases during cognitive tasks. In addition to using more complex tasks, Bruder and
his associates have examined the issue of asymmetry in the evoked potentials of de-
pressed and nondepressed subjects (e.g., Bruder et al., 1995; Tenke et al., 1993).
They have recorded evoked potentials during spatial and temporal discrimination
tasks and have found that control subjects who had a strong left ear (right hemi-
sphere) advantage during a complex tone task had right greater than left P3 ampli-
tudes. This asymmetry was seen at different sites across the hemisphere. Depressed
subjects, in addition to having lower P3 amplitudes than controls, did not show this
normal right greater than left asymmetry (Bruder et al., 1995). In a study compar-
ing typical and atypical depressed subjects, Bruder et al. (1991) found that typical
depressed subjects had a longer P3 latency in an audiospatial task but not a tempo-
ral task than did normal controls and atypical depressed subjects. This investigation
also found that the P3 latency in typical depressed subjects was longer for stimuli
presented to the right hemifield (i.e., left hemisphere) than to the left hemifield.
Atypical depressed subjects and normal controls did not show this asymmetry.
In summary, studies have failed to demonstrate consistent differences in P3
amplitudes between depressed and nondepressed subjects (e.g., Bruder et al.,
1995; Diner, Holcomb, & Dykman, 1985; Giedke, Thier, & Bolz, 1981). The
performance of a right hemisphere task, but not a left hemisphere task, however,
is associated with increased P3 latency in typical depressed subjects (Bruder et
al., 1995) and with a lack of the relative right-sided asymmetry in P3 amplitude
seen in controls (Tenke et al., 1993), providing some evidence of impairment in
right posterior function in depression, although the significance of latency dif-
ferences in P3 is not entirely clear.
STUDIES OF CEREBRAL METABOLISM AND BLOOD FLOW
Studies of regional cerebral blood flow (rCBF) and glucose metabolism have the
advantage over EEG and ERP studies of being able to provide better spatial res-
olution, and, furthermore, recent advances allow rCBF and glucose metabolism
studies to assess the functions of subcortical structures, which measures of brain
electrical activity cannot do. The increase in spatial resolution is, however, ac-
companied by a loss of temporal resolution and an increase in cost. Both me-
tabolism and blood flow studies use a radioactive tracer to examine cerebral ac-
tivation. The supposition underlying these studies is that increased neuronal
activation is accompanied by an increase in metabolism and an associated in-
crease in blood flow.
A particularly important methodological issue in the assessment of lateralized

changes in neuroimaging studies is how putatively asymmetrical changes are
measured. In most neuroimaging studies, if a focus of activation exceeds an ar-
bitrary statistical threshold in one hemisphere but not in the other, a lateralized
effect is reported. A formal test of the Hemisphere X Condition or Hemisphere
X Group interaction must, however, be performed. This interaction test formally
assesses whether the change in one hemisphere is significantly different from the
change in the opposite hemisphere. Without such a test of the interaction term,
it is simply not possible to know whether a reported lateralized effect is indeed
truly asymmetrical. For example, if a focus exceeds threshold in one hemisphere
and falls just below threshold in the other hemisphere, a lateralized effect would
be claimed yet a formal test of the interaction would show that the interaction
was clearly not significant. In addition, it is possible for there to be a significant
interaction without any of the main effects being significant. Thus, we must ex-
ercise considerable caution in interpreting putatively lateralized changes that have
been reported in the recent neuroimaging studies of emotion.
Blood Flow Studies of Induced Sadness
It was not until recently that investigators began to use rCBF technologies to
study sadness, and, in contrast to studies of depression, most have found that sad-
ness is associated with increased cerebral activation. In a study in which subjects
were asked to recall or imagine a sad event, sadness was associated with in-
creases in the inferior and orbitofrontal regions (Pardo, Pardo, & Raichle, 1993).
Among women these increases were bilateral, whereas among men these in-
creases were seen only in the left hemisphere. Because these investigators only
compared the sad mood to a resting control condition, it is unclear how much of
the observed increases were specific to sadness rather than to the processes in-
volved in memory retrieval and imagery per se.
In a study that examined both happiness and sadness, sadness was associated
with increased global blood flow relative to a neutral mood, whereas happiness was
associated with decreased global blood flow (Schneider et al., 1994). Mood changes
were induced by having the subjects view happy and sad facial expressions and
asking the subjects to try and experience the mood being displayed. The efficacy
of the mood induction was assessed with the Positive and Negative Affective Sched-
ule scales, and the investigators found a significant correlation between the increase
in negative mood reported and the increase in cerebral blood flow. The frontal poles
were the only regions that showed lateralized differences between the emotions:
Sadness was associated with left greater than right blood flow, whereas happiness
was associated with right greater than left blood flow in this region. However, the
three-way interaction of Region, Hemisphere, and Emotion condition was clearly
not significant, casting some doubt on this specific finding.
A subsequent study by the same group did not find any global differences in
blood flow between happy and sad induced moods (Schneider et al., 1995). They
did report significant differences in subcortical blood flow such that sadness was
associated with increased left and decreased right CBF in the amygdala, increases
in the caudate, and decreases in the mamillary body and posterior cingulate. Al-
though there were no cortical asymmetries, there was a trend for increased left
frontotemporal blood flow to be associated with increased reports of both nega-
tive and positive affect. George et al. (1995) found that sadness relative to hap-
piness was associated with bilateral increases in the prefrontal cortex, the thala-
mus, and the basal ganglia and with increases in the right anterior cingulate.
Highlighting the importance of comparing sadness to another emotional state,
when these investigators compared sadness to a neutral condition there was a dif-
ferent pattern of increased activation, including an increase in the left lateral pre-
frontal region and bilateral increases in the anterior cingulate.
Baker, Frith, and Dolan (1997) recently found that both elated and depressed
mood states were associated with bilateral increases in orbitofrontal blood flow
and with increased blood flow in the superior region of the left dorsolateral pre-
frontal cortex and in the right lateral premotor area. These investigators used a
combination of the Velten technique (Velten, 1968) and music (portions of "Rus-
sia under the Mongolian Yoke" from Prokofiev's score for "Alexander Nevsky"
played at half speed) to induce a depressed mood. Relative to the neutral condi-
tion, depressed mood was also associated with increases in the posterior cingu-
late cortex. Decreases in CBF were observed in the right caudate, the right dor-
solateral prefrontal cortex, and the bilateral rostral medial prefrontal cortex.
Unfortunately, these investigators did not directly compare the elated and de-
pressed moods. Moreover, subjects were performing cognitive tasks during the
time that the positron emission tomography (PET) data were acquired, and it is
not clear whether the mood effects persisted throughout cognitive task perfor-
mance. Additionally, a formal statistical assessment of the lateralized changes
was not performed.
Another recent study examined film-induced and recalled happiness, sadness,
and disgust and found that all three emotions were associated with increased ac-
tivation in the prefrontal cortex, the thalamus, and bilateral regions within the
anterior temporal cortex (Lane et al., 1997). In addition, sadness was associated
with unique increases in activation in the caudate, putamen, lateral cerebellum,
and the cerebellar vermis. There were no significant asymmetries observed.
Only Gemar et al. (1996) have reported on decreases in activation in response
to induced sadness. These investigators found that, in contrast to a neutral recall
condition, self-generated sadness was associated with decreases in blood flow in
the left dorsolateral prefrontal cortex, the left medial prefrontal cortex, and the
left temporal cortex. The investigators also included a resting control condition,
and, when the self-generated sadness condition was compared with the resting
control condition, a different pattern of findings emerged, thus underscoring the

critical importance of the control condition in such neuroimaging studies.
Blood Flow Studies of Depression
A different pattern emerges from the literature on depression. One of the earli-
est studies found that depressed subjects had significantly lower gray matter flow
in the left hemisphere than did controls (Mathew et al., 1980). The pattern of
flow reduction in the right hemisphere was similar but not significant. Just as the
initial investigations of stroke-induced mood changes did not consider the issue
of location within the hemisphere (e.g., Black, 1975), this study examined ac-
tivity only on the hemispheric level. Global decreases in both the right and left
hemispheres of unipolar depressed subjects have been reported by a number of
investigators (Bonne & Krauz, 1997; Gustafson, Risberg, & Silfverskiold, 1981;
lidaka et al., 1997; Mayberg et al., 1994; Rush et al., 1982; Sackeim et al., 1990;
Warren et al., 1984). Regions with the largest decrease in rCBF include selec-
tive frontal, superior temporal, central, and anterior parietal regions (Sackiem et
al., 1990), as well as inferior frontal and cingulate cortex (Mayberg et al., 1994),
and the severity of depression has been correlated with the magnitude of the bi-
lateral decreases in frontal activity (lidaka et al., 1997).
Using single photon emission computerized tomography (SPECT), Delvenne et
al. (1990) examined a group of 38 depressed and 16 control subjects. Activity in
a slice 5 cm above the orbitomeatal line revealed that subjects classified as bipo-
lar and/or endogenous had significantly lower left than right activity, but the hemi-
spheric differences between controls and unipolar subjects were not significant.
This reduction in left hemisphere flow was most pronounced in the frontal region.
Reischies, Hedde, and Drochenir (1989) found that depressed subjects in both the
acute and remitted phases had a pattern of relative right-sided frontal activation
compared with controls, who had relative left-sided asymmetry in this region. In-
vestigators using 195mAu in the measurement of CBF found that depressed subjects
had significantly lower CBF in the left frontal and in all of the right hemisphere
regions (frontal, temporal, parietal, and occipital) than did a group of normal con-
trol subjects (Schlegel et al., 1989). There was an age difference between the two
groups, and this may have accounted for some of the observed differences. With
the regional means provided by the authors, however, and computation of a
frontal/hemisphere ratio, which eliminates the problem of differences in overall
flow between the two groups, the data show that depressed subjects have lower
frontal/hemisphere ratios than do controls, and this between-group difference is
largest in the left hemisphere. Bilateral prefrontal decreases have also been reported
by other authors (Chabrol et al., 1986; Ito et al., 1996; Schroeder et al., 1989).
A study of elderly depressed subjects found global decreases in rCBF com-
pared with controls (Lesser et al., 1994). Using Tc-HMPAO as a tracer, the in-
vestigators found bilateral decreases in the orbital frontal, inferior temporal, and
parietal regions in addition to global decreases in blood flow throughout the right
hemisphere. Global flow decreases in elderly depressed subjects have also been
found by other investigators (Hoyer, Oesterreich, & Wagner, 1984; Philpot et al.,
1993).
Investigators at Hammersmith Hospital in London, England, have produced a
large body of data on this topic over the last 5 years. Using PET measures of
CBF, Bench et al. (1992) found that depressed subjects, in contrast to nonde-
pressed controls, had decreased flow in a region consisting of the left anterior
cingulate and the left dorsolateral prefrontal cortex. A subsequent study repli-
cated these findings in another 40 depressed subjects (Bench et al., 1993). Rat-
ings of patient symptomatology were subjected to a principal components analy-
sis, and three factors were identified. The first factor was anxiety and
psychomotor agitation, which was associated with an increase in blood flow in
the right posterior cingulate and bilateral increases in the inferior parietal lob-
ules. The second factor was depression and psychomotor retardation, and this
was associated with decreases in the following regions in the left hemisphere:
dorsolateral prefrontal cortex, inferior frontal, superior temporal, and inferior
parietal. The final factor was cognitive impairment as identified by the Mini-
Mental State Examination (MMSE), and this was associated with decreased flow
in the left medial prefrontal cortex, the right anterior thalamus, the right supe-
rior temporal gyrus, and the right postcentral gyrus. More than half of these sub-
jects were rescanned following treatment. Recovery was found to be associated
with increased blood flow in the left dorsolateral prefrontal cortex, bilateral re-
gions in the medial prefrontal cortex including the anterior cingulate, and in a
region of the posterior parietal cortex (Bench, Frakowiak, & Dolan, 1995). Ital-
ian investigators found similar results: Depressed subjects had decreased left
frontal blood flow, and, when they were rescanned after 6 months of tricyclic
antidepressant therapy, these subjects had increases in these regions. Similar find-
ings were obtained with the dopamine agonist amineptine (Passero, Nardini, &
Battistini, 1995).
Somewhat contradictory results were reported by Drevets et al. (1992). Like
the Hammersmith group, these investigators used 15O, but they used a bolus in-
jection instead of inhalation. The implications of these different methods is that
an injection of 15O results in a scan reflecting approximately 40 seconds of ac-
tivity in comparison with about 10 minutes of data obtained with 15O inhalation.
Drevets et al. (1992) reported that depressed subjects with a family history of
depression had increased activation in the left orbitofrontal region compared with
controls. Interestingly, they did observe a significant correlation (r = —0.62) be-
tween depression and left frontal activation in the dorsolateral region such that
increased severity of depression was associated with decreased activation in this
left anterior region. Furthermore, a recently published study by this group reports
decreased activation in a subgenual region of the left prefrontal cortex among a

more heterogeneous group of depressed subjects relative to nondepressed con-
trols (Drevets et al., 1997).
Other researchers who have not found decreases in left anterior blood flow in-
clude Silfverskiold and Risberg (1989), who found no global or regional differ-
ences between depressed subjects and a group of age- and sex-matched controls.
Gur et al. (1984) examined a group of medicated unipolar depressed subjects and
found that they did not significantly differ from controls in the pattern and over-
all level of CBF. Nonsignificant group differences in rCBF were also reported
by Maes et al. (1993). Uytdenhoef et al. (1983) found that depressed subjects
had increased left frontal flows as well as decreased flows in the right posterior
region, but it is unclear if there was any control for type I error in this study.
Higher global flow values in depressed subjects than in controls were reported
by Rosenberg et al. (1988). Surprisingly, the depressed subjects were older than
the controls, which would lead us to expect overall decreases in activation (see
above).
To summarize, studies of depression, in contrast to studies of induced sadness,
have typically reported decreased left frontal blood flow (Bench et al., 1992,
1993; Delvenne et al., 1990; Passero, Nardini, & Battistini, 1995), and recovery
has been found to be associated with increases in these regions (Bench et al.,
1995; Passero, Nardini, & Battistini, 1995). Likewise, Drevets et al. (1992) found
a negative relation between left dorsolateral prefrontal blood flow and symptom
severity. A comparable number of investigators have found that depressed sub-
jects are characterized by global decreases in blood flow (Bonne & Krausz, 1997;
Gustafson, Risberg, & Silfverskiold, 1981; Mathew et al., 1980; Mayberg et al.,
1994; Rush et al., 1982; Sackeim et al., 1990; Warren et al., 1984). Global de-
creases in blood flow are also typical of elderly depressed subjects (Hoyer, Oester-
reich, & Wagner, 1984; Lesser et al., 1994; Philpot et al., 1993).
Studies of Glucose Metabolism in Depression
Although no studies have yet been done examining patterns of glucose metabo-
lism during the induction of sadness, the results of metabolism studies of de-
pression are mostly consistent with results in the rCBF literature. An early study
of glucose metabolism in a small group of unipolar and bipolar depressed sub-
jects did not find any differences in left/right asymmetry for the frontal cortex
(Baxter et al., 1985), but a subsequent study indicated that this failure to find a
consistent decrease in left frontal activation among the depressed subjects was
because of the concurrent decrease in right frontal activation (Baxter et al., 1989).
In this study, the ratio of the metabolic rate for the left dorsal anterolateral pre-
frontal cortex to whole hemisphere was significantly lower in depression. Re-
covery from depression was associated with increases in this index. Among bipo-
lar and unipolar depressed subjects this ratio was also decreased in the right hemi-
sphere, but it was only the reduced left prefrontal to whole hemisphere ratio that
distinguished all three types of depression studied: unipolar depression, bipolar
depression, and obsessive-compulsive disorder with depression. Bilateral de-
creases in frontal metabolism have also been reported by other groups (Biver et
al., 1994; Francois et al., 1995). Biver et al. (1994) also found bilateral decreases
in parietal metabolism.
Austin et al. (1992) reported that depressed subjects had decreased overall me-
tabolism compared with controls. After controlling for age, medication, and en-
dogenous subtype, they found a significant negative correlation between anterior
activation and Hamilton Rating Scale for Depression (HRSD) scores. As in the
Baxter et al. (1989) study, this negative relation was seen bilaterally. Global de-
creases in metabolism were also found in a small sample of depressed subjects
with seasonal affective disorder (SAD) (Cohen et al., 1992). In contrast with
other studies, Cohen et al. (1992) also found frontal asymmetry differences be-
tween groups such that depressed subjects had left greater than right metabolic
activity in an anterior frontal region in contrast to controls who had greater rel-
ative right-sided activation. This result, however, emerged from unprotected
t-tests comparing the groups across 26 different regions of interest. The finding
they report disappears following Bonferroni correction. Moreover, the data are
based on a sample of seven patients with seasonal affective disorder.
In a small study of 10 bipolar and unipolar depressed subjects, Martinot et al.
(1990) found that depressed subjects had a significantly higher right/left ratio in
the prefrontal cortex than did controls. This asymmetry was the result of de-
creased left prefrontal metabolism in the depressed subjects. Depressed subjects
also had a relative hypofrontal pattern of activation compared with controls, who
had more anterior than posterior activation. Although recovery was associated
with an increase in left prefrontal metabolism such that there was no asymme-
try, euthymic depressed subjects still had a pattern of hypofrontal activation. In
a study of bipolar subjects, Kato et al. (1995) found that depression was associ-
ated with a decrease in left frontal metabolism and that left frontal metabolism
was correlated negatively with HRSD scores. Bipolar subjects scanned in manic
and euthymic states had decreased right frontal metabolism compared with con-
trols. Negative correlations between left frontal metabolism and HRSD scores
have also been found in a sample of bulimic subjects (Andreason et al., 1992).
Nonsignificant differences were reported by Buchsbaum et al. (1984). Their use
of a series of shocks to the subjects' right forearm during FDG uptake may, how-
ever, have obscured group differences in asymmetry by increasing activity in the
left hemisphere.
Like rCBF, global metabolic decreases in elderly depressed subjects have been
reported (e.g., Kumar et al., 1993). Studies of elderly subjects with Parkinson's
disease have found that it is bilateral decreases in the frontal region that distin-
guishes patients with and without depression (Mayberg et al., 1990; Ring et al.,
1994).
In most of the metabolism and rCBF studies reviewed here, decreased left
frontal activation was found during depression. The reports are mixed as to
whether these decreases occur in only the left hemisphere (e.g., Bench et al.,
1992, 1993; Delvenne et al., 1990; Martinot et al., 1990) or in both the left and
right frontal regions (e.g., Baxter et al., 1989; Chabrol et al., 1986; Francois et
al., 1995; Sackeim et al., 1990; Schroeder et al., 1989). In several studies, acti-
vation in the prefrontal regions of the left hemisphere was negatively correlated
with severity of depression (Andreason et al., 1992; Baxter et al., 1989; Bench
et al., 1993; Drevets et al., 1992; Kato et al., 1995), and a number of investiga-
tors have found that remission is associated with reversal of the observed left
frontal hypoactivation (Baxter et al., 1989; Bench et al., 1995; Martinot et al.,
1990; Passero, Nardini, & Battistini, 1995). When the depressed subjects are
older, bilateral decreases appear to be more prevalent (e.g., Hoyer, Oesterreich,
& Wagner, 1984; Kumar et al., 1993). Decreased activation in the posterior re-
gions has been reported for the right side (e.g., Schlegel et al., 1989; Uytdenhoef
et al., 1983) and for both sides (e.g., Biver et al., 1994; Lesser et al., 1994; Sack-
iem et al., 1990).
In a new study in our laboratory, Abercrombie et al. (1998) found that, among
depressed patients, PET-derived measures of glucose metabolism in the amyg-
dala predicted the severity of dispositional NA (see Figs. 11.1 and 11.2). These
findings, along with a similar observation by Drevets et al. (1992), suggest that
Figure 11.1. Illustration of PET-MRI coregistration and amygdalar region of interest de-
lineation. Representative image planes in the coronal orientation for one participant are
shown. The PET image plane is presented beside its corresponding coregistered MRI
plane. Units of the PET color scale are in mg/100 g/min. Glucose metabolism extracted
according to these MR-defined regions of interest was then used for the correlational
analysis depicted in Figure 11.2. (Adapted from Abercrombie et al., 1998.)
Figure 11.2. Scatter plot of correlation in depressed subjects (N = 17; r(15) = 0.56; P <
0.02) between dispositional negative affect (assessed with the PANAS Negative Affect
Scale—Trait Version; Watson, Clark, & Tellegen, 1988) and glucose metabolism in the
right amygdala (residualized for global metabolic rate). (Adapted from Abercrombie et
al., 1998.)
variations in activation in the amygdala play an important role in determining

the intensity of NA exhibited by depressed patients. In light of the role of the
amygdala in a broad constellation of NA characteristics that include several dif-
ferent anxiety disorders (see Davidson & Irwin, 1998), it may well be that amyg-
dala activation accounts for some of the comorbidity between anxiety and de-
pression.
SUMMARY
It is clear from this review that there are a host of conceptual and methodologi-
cal issues that still plague research on this topic. We believe that the most fruit-
ful general approach has been and will continue to be the examination of rela-
tions between measures of emotional state and/or symptoms and specific patterns
of regional brain activity. There appear to be fewer replicated findings in the lit-
erature on the effects of experimentally induced sadness on regional brain func-
tion than in the literature on depression. In part, this lack of consistency is a func-
tion of the failure of investigators to independently verify the presence of sadness.
Another major contributor to the inconsistency among studies is the variability
in control conditions that have been used. It is essential that investigators attempt
to isolate specific features of sadness while controlling for sensory, perceptual,
and memorial processes associated with the specific form of emotion elicitation.
It is also important to include more than one emotion in these studies to ascer-
tain whether the observed effects are indeed specific to sadness or are more gen-
eral characteristics of emotion per se. Most of the neuroimaging studies of sad-
ness have used injected O15 water as a tracer. This results in an uptake period of
about 40 seconds. Such studies depend on very critical timing in the presenta-
tion of the activation condition in relation to tracer injection. Fluctuations in the
intensity of elicited emotion during this critical period will affect the data
obtained.
The literature on depression is somewhat more consistent, though many dif-
ferent patterns of regional brain abnormalities have been reported. Here it is im-
portant to emphasize the obvious point that considerable heterogeneity exists in
the symptoms of depression, even among very carefully diagnosed patients meet-
ing specific DSM-IV criteria. The strategy pioneered by Bench, Dolan, and their
colleagues to examine relations between specific symptom clusters and patterns
of regional brain function is particularly helpful. With such a strategy, the het-
erogeneity among patients can be harnessed to one's advantage in dissecting those
circuits that appear to vary with changes in specific patterns of symptoms. A fur-
ther refinement of this strategy would include testing patients on objective lab-
oratory measures of emotional reactivity and emotion regulation and then ex-
amining the relations between specific patterns of performance on these
laboratory tasks and measures of regional brain function (see Davidson, 1998).
Another important strategy for future research is to examine regional brain func-
tion in patients who are performing tasks under different incentive and feedback
conditions because extant evidence suggests that depressed patients may be un-
derresponsive to reward (e.g., Henriques, Glowacki, & Davidson, 1994) as well
as overresponsive to negative feedback (Elliott et al., 1997).
Finally, studies that combine neurochemical and functional neuroanatomical
approaches to characterize regional neurochemical abnormalities are needed. For
example, Mann and colleagues (1996) recently examined differences in regional
glucose metabolism between depressed patients and healthy controls in response
to fenfluramine, a serotonin agonist. Healthy controls showed significant in-
creases in metabolism in left prefrontal and temporoparietal cortex and decreases
in right prefrontal cortex, while depressed patients failed to show any significant
change in response to the drug. These findings implicate abnormalities in later-
alized prefrontal serotonergic function in depression. Although in need of repli-
cation, this finding helps to integrate the previously disparate reports on the neu-
rochemistry and functional neuroanatomy of depression. The effects of treatment,
particularly with medications that affect the serotonin system, on these lateral-
ized abnormalities in serotonin function require study.
On the question of whether sadness in normal people is a good model system
for clinical depression, the data are inconsistent. It is likely that cumulative ex-
posure to depression will exert effects that are not going to emerge with brief
mood inductions in normal people. On the other hand, there may be some fea-
tures of the response that are similar, but any firm conclusions on this point must
await more methodologically sophisticated studies that use appropriate control
groups, statistical methods, and procedures to independently verify the presence
of the intended emotion. We now have the tools to make rapid advances in the
study of brain function and emotion in intact humans, and we expect much
progress in the next decade.
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12
Anxiety, Stress, and Cortical Brain Function
JACK B. NITSCHKE, WENDY HELLER,

AND GREGORY A. MILLER
Much has been written about the survival value of panic and the benefits of anx-
iety for various aspects of human performance (e.g., Barlow, 1991; Lang, 1985;
Miller & Kozak, 1993). Anxiety can be maladaptive, however, disrupting per-
formance and interfering with both psychological and physical well-being. Con-
sequently, the current, 4th edition of the Diagnostic and Statistical Manual of
Mental Disorders (DSM-IV; American Psychiatric Association, 1994) distin-
guishes 11 different diagnoses it classifies as anxiety disorders.
The prevalence of anxiety disorders has led to an interest in the neural mech-
anisms that accompany them. The search for the brain circuitry of anxiety has
benefitted from a large data base of animal research (e.g., Davis, 1992; Gray,
1982; LeDoux, 1993, 1995; Mineka, 1985), possible in part because of the ease
of experimentally conditioning fear. Although research has greatly elucidated the
subcortical circuits mediating fear in animals, the precise role of the cortex in
human anxiety has eluded understanding.
The interpretation of neuropsychological studies based on electrophysiologi-
cal, hemodynamic (blood flow), and behavioral methods has been hindered by
inconsistencies in findings for particular cortical brain regions. Although many
studies have reported or inferred asymmetries in regional cortical activity and
function, the regions involved and the direction of the asymmetry have varied,
as reviewed below. Methodological differences from study to study, albeit im-
298
Anxiety, Stress, and Cortical Brain Function 299
portant, do not provide a cogent explanation for the conflicting patterns of brain
activity reported in the literature.
Heterogeneity among the samples studied may explain the inconsistencies in
the literature on brain function in anxiety. Research has been conducted on sam-
ples characterized by specific anxiety disorders as defined by the several DSM
editions, by self-reports of anxiety on various questionnaires, and by experi-
mentally induced anxiety. In recent work, we suggested that distinguishing be-
tween types of anxiety, which would be differentially represented in different
subject samples, may help to resolve some of the discrepancies in the literature
(Heller et al., 1997a; Heller & Nitschke, 1998; Nitschke et al., 1999).
In this chapter, we review the evidence connecting distinct types of anxiety
with specific patterns of regional brain function and examine the implications of
these associations for cognition. In addition, we consider the role of stress in anx-
iety and explore the relationships among stress, anxiety, and regional brain
activity.
TWO TYPES OF ANXIETY
There is considerable disagreement as to the meaning of anxiety and its rela-

tionship to fear, panic, stress, and worry (e.g., Barlow, 1991; Borkovec et al.,
1983; Eysenck, 1957; Heller & Nitschke, 1998; Heller et al., 1997a; Klein, 1981,
1987; Lang, 1968, 1978, 1985; Lazarus, 1993; Mathews, 1990; Miller & Kozak,
1993; Molina & Borkovec, 1994; Watson et al., 1995). Eysenck (1991) adheres
to the traditional conditioning view that anxiety is a learned kind of fear. In con-
trast, Gray (1982, 1991) argues that anxiety encompasses both a fear state that
is elicited by certain conditioned stimuli associated with punishment and antici-
patory frustration elicited by other types of stimuli. Barlow (1991) distinguished
fear from anxiety and argued instead that panic and fear are the same. In keep-
ing with the categorization of anxiety disorders in the DSM-IV, we view anxi-
ety as subsuming fear, panic, and worry.
In recent work, we have focused on two types (or dimensions) of anxiety that
can be psychometrically distinguished (Nitschke et al., 2000) and that may ac-
count for the varied findings in research examining brain activity in anxiety (see
Table 12.1). In accord with Barlow (1991), we defined one of these types as anx-
ious apprehension, also referred to as worry (e.g., Borkovec et al., 1983), cog-
nitive anxiety (e.g., Lehrer & Woolfolk, 1982; Schwartz, Davidson, & Goleman,
1978), anticipatory anxiety (e.g., Klein, 1981), and anticipatory frustration (e.g.,
Amsel, 1962). Anxious apprehension is characterized by a concern for the future
and verbal rumination about negative expectations and fears. It is often accom-
panied by muscle tension, restlessness, and fatigue. Unlike Barlow, we do not
equate anxiety with anxious apprehension.
Table 12.1. Characteristics of Anxious Apprehension and Anxious Arousal

ANXIOUS APPREHENSION ANXIOUS AROUSAL
Cardinal feature Verbal rumination involving Intense, immediate fear

negative expectations
or fears about future
Time scale Ranging from immediate Present or very
to distant future immediate future
Related or synonymous Worry, cognitive anxiety, Panic, somatic anxiety
constructs anticipatory anxiety
Somatic symptoms Muscle tension Increased heart rate,
shortness of breath,
dizziness, sweating,
feeling of choking
General Left-hemisphere Right-hemisphere
neuropsychological engagement engagement
patterns*
*Neuropsychological inferences based on electrophysiological, hemodynamic, and behavioral find-
ings in anxiety.
The second type of anxiety is anxious arousal, often referred to as somatic

anxiety (e.g., Lehrer & Woolfolk, 1982; Schwartz, Davidson, & Goleman, 1978).
Anxious arousal is the predominant type of anxiety present in panic. In addition
to feelings of fear, anxious arousal is associated with such somatic symptoms as
pounding heart and dizziness (Watson et al., 1995) but not with somatic features
associated with anxious apprehension (e.g., muscle tension). Anxious arousal is
more likely to be triggered by a threat perceived to represent an immediate dan-
ger, whereas anxious apprehension would be more salient for a threat that in-
vokes fear and worry about the more distant future.
Of conceptual import, our distinction between anxious apprehension and anx-
ious arousal does not correspond precisely to the distinction between trait anxi-
ety and state anxiety. Trait anxiety is typically characterized by a disposition to
worry, to be tense, and to interpret stressful situations as threatening (e.g.,
Eysenck, 1992; Spielberger, 1983). Most self-report measures of trait anxiety as-
sess anxious apprehension and negative affect. A disposition toward anxious
arousal could, however, be a trait characteristic.
On the other hand, state anxiety is generally associated with a more immedi-
ate fear response accompanied by those somatic symptoms characteristic of anx-
ious arousal. A panic attack would be an extreme manifestation of state anxiety.
Although not as common, state anxiety characterized by anxious apprehension
could be induced by a specific stressor that elicits worry. Indeed, the presence
of either type of anxiety in an individual is not static: Stressful events, social sup-
port, and coping skills can modulate one's level of each type of anxiety.
Available research suggests that anxious apprehension and anxious arousal are
not mutually exclusive (e.g., Dien, 1999; Heller et al., 1997a). It follows that anx-
ious apprehension and anxious arousal would be present to varying degrees in the
different anxiety disorders. Anxious apprehension is particularly prominent in gen-
eralized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD) in
which worry and other cognitive symptoms predominate. In addition, GAD in-
cludes the subset of somatic features outlined above for anxious apprehension.
Moreover, a cardinal feature of specific phobia, social phobia, and agoraphobia is
persistent, excessive fear that usually reflects concern about the future. Panic dis-
order includes worry about having additional panic attacks and about the implica-
tions or consequences of an attack. In those disorders in which panic attacks may
occur, such as panic disorder, specific phobia, and social phobia, DSM-IV criteria
clearly indicate the presence of anxious arousal. Furthermore, there are likely to
be individual differences and situational factors that influence the relative frequency
and occurrence of each type of anxiety in a particular person.
The importance of taking into account the relative admixture of both types of
anxiety becomes apparent when we consider the findings reviewed below show-
ing that each type of anxiety is associated with distinct patterns of brain activ-
ity. In turn, our distinction between anxious apprehension and anxious arousal
may help to explain the cognitive findings reported for anxiety.
STRESS AND ANXIETY
Stress is an important factor influencing the relationship between types of anxi-

ety and brain function. In numerous neuropsychological and cognitive studies,
researchers have employed stressful experimental conditions to elicit state anxi-
ety, which, as noted above, is likely to involve anxious arousal as well as anx-
ious apprehension.
The term stress has most often been used to refer to an external phenomenon
(a stressor) that has an emotional impact on an individual. Many researchers have
also, however, invoked the term stress to imply psychological stress, defined as
the emotional response to an external event or stressor. Lazarus and colleagues
have emphasized the interactive relationship between these two aspects of stress,
arguing that potential stressors can be appraised as indicative of harm, threat, or
challenge (for review, see Lazarus, 1993).
The distinction between potential sources of stress and the emotional seque-
lae that ensue is critical to an understanding of anxiety. Lazarus and others have
shown that a one-to-one correspondence between a potential stressor and a sub-
sequent emotional response does not exist (Lazarus, 1993). Rather, there are large
individual differences in response to any particular event, and many factors (e.g.,
life history, coping style, trait anxiety) influence the degree to which an event is
appraised as harmful or threatening. For example, anticipation of a public speech
might not elicit anxiety in a college professor with years of experience but is
likely to do so in a graduate student giving a talk at a conference for the first
time. Thus, a thorough understanding of the relationship between stress and anx-
iety must take into account not only specific and contextual external conditions
involved but also the role of individual differences in response to those condi-
tions. The importance of this issue can perhaps be seen most clearly in the height-
ened vulnerability of trait-anxious people to exhibit cognitive abnormalities (e.g.,
attentional biases to threat) in response to various stressors (see discussion of
cognitive studies of anxiety, below).
In a review of the neuropsychological and cognitive literatures on anxiety, it
is important to consider the role of stressors, which often elicit anxious appre-
hension and anxious arousal, as well as the role of both types of anxiety as forms
of psychological stress. Experimental manipulations of stressful situations, such
as electrical shock, can be used to elicit anxious arousal. Similarly, researchers
have often designed experiments to take advantage of stressful life circumstances,
such as final examinations for medical students. In addition, a large literature
about the effects of major life events and daily hassles has documented that life
stress precipitates a variety of psychopathological states, including anxiety (e.g.,
Faravelli & Pallanti, 1989; Pollard, Pollard, & Corn, 1989; Rapee, Litwin, & Bar-
low, 1990; Roy-Byrne, Geraci, & Uhde, 1986). Electrical shock, final examina-
tions, major life events, and daily hassles are examples of potential stressors that
can result in psychological stress, such as anxious apprehension or anxious
arousal. In the following sections, it will be apparent that stress is often a key
variable in the association between anxiety and region-specific brain function.
NEUROPSYCHOLOGICAL STUDIES OF ANXIETY
We have proposed a neuropsychological framework for anxiety based on the two

types of anxiety distinguished above (Heller et al., 1997a; Heller & Nitschke,
1998). Given the left-hemisphere dominance for language in most right-handed
people, we have hypothesized that anxious apprehension would be associated
with more left-hemisphere activity because of the strong verbal component in-
herent in worry and cognitive anxiety. Conversely, consistent with a neuropsy-
chological model of emotion proposed by Heller (1990), the literature linking so-
matic arousal to posterior right-hemisphere regions of the brain (for review, see
Heller, Nitschke, & Lindsay, 1997b) suggested to us that anxious arousal should
be associated with more right posterior activity.
In addition, of relevance to both types of anxiety, unpleasant valence and neg-

ative affect have been shown to be associated with increased right anterior ac-
tivity (for review, see Davidson, 1992, 1998; Heller, 1990; Heller & Nitschke,
1997). The effect of unpleasant valence on anterior brain activity in anxious ap-
prehension is difficult to anticipate. The greater right than left anterior activity
associated with unpleasant valence might serve to cancel the increase in left an-
terior activity expected for anxious apprehension. Alternatively, anxious appre-
hension might be associated with a bilateral increase in anterior activity. Due to
the presence of unpleasant valence, anxious arousal should be associated with
increased activity in right anterior as well as right posterior regions of the brain.
Electrophysiological and Hemodynamic Paradigms
The distinction between anxious apprehension and anxious arousal is well sup-
ported in the literature on regional brain activity. Increased left-hemisphere ac-
tivity has been associated with anxiety in studies on populations better charac-
terized by anxious apprehension than by anxious arousal. In a positron emission
tomography (PET) study, Baxter et al. (1987) reported greater regional cerebral
blood flow (rCBF) in the left orbital gyrus in OCD patients than in depressed
and control participants. Similarly, Swedo et al. (1989) found that OCD patients
showed more left orbital frontal and left anterior cingulate metabolism than
nonpsychiatric controls. Wu et al. (1991) reported higher relative metabolism in
the left inferior frontal gyrus for GAD patients than for nonpsychiatric controls.
In another study, inpatients with GAD showed increases in left orbital frontal
blood flow when asked to freely associate about threatening pictures presented
before rCBF measurement (Johanson et al., 1992). Relative increases in activity
for left subcortical regions (e.g., caudate, putamen, and thalamus) have also been
reported in a number of studies (e.g., Fredrikson et al., 1993; Swedo et al., 1989).
Similar results have been obtained with electroencephalography (EEG). Using
only left-hemisphere and midline leads, Buchsbaum et al. (1985) reported that
GAD patients had more activity (less delta and alpha) than nonpsychiatric con-
trols. Consistent findings were reported by Carter, Johnson, and Borkovec (1986)
for beta activity in students classified as "worriers" or "nonworriers" when asked
to "worry about a specific topic of personal concern."
Conversely, those authors reporting increased right-hemisphere activity in anx-
iety examined populations characterized by anxious arousal or employed exper-
imental designs manipulating it. Using PET, Reiman et al. (1984) found that pa-
tients with panic disorder showed greater right-hemisphere than left-hemisphere
blood flow, blood volume, and metabolic rate in the parahippocampal gyrus,
whereas normal controls demonstrated no such asymmetry. In a single photon
emission computerized axial tomography study, panic disorder patients who ex-
perienced a sodium-lactate-induced panic attack were found to have a signifi-
cantly greater increase in right occipital blood flow than did patients who did not
panic and controls (Stewart et al., 1988).
Consistent with this pattern, glucose metabolism changes indicative of in-
creased right-hemisphere activity for GAD patients performing a Continuous Per-
formance Task designed to induce anxious arousal were reported in two studies
(Buchsbaum et al., 1987; Wu et al., 1991). In recent EEG work, Davidson et al.
(2000) reported increased right anterior temporal, right lateral prefrontal, and
right parietal activity in social phobics immediately before making a public
speech, an experimental manipulation likely to elicit anxious arousal. Spider pho-
bia has also been found to be associated with more right than left parietal activ-
ity (Merckelbach et al., 1999). In sum, across a number of different imaging tech-
nologies and experimental protocols, the increased right-hemisphere activity
expected for anxious arousal emerges consistently in clinical populations.
Similar findings have emerged in nonclinical samples as well. When the state
version of the State-Trait Anxiety Inventory (STAI; Spielberger, 1968, 1983) was
administered immediately after arterial and venous catheterization and again af-
ter completion of the PET scans, high-anxious subjects had greater right than left
blood flow, whereas low-anxious subjects showed no differences between the
hemispheres (only frontal regions were measured; Reivich, Gur, & Alavi, 1983).
In a population of nonpsychiatric volunteers, those administered diazepam in-
travenously showed decreases in rCBF across all cortical regions, particularly in
the right frontal area, whereas those injected with a placebo showed no rCBF
changes (Mathew, Wilson, & Daniel, 1985).
In an event-related potential (ERP) study, participants who scored high on both
the trait and state versions of the STAI showed smaller N2 and P3 amplitudes
over the right hemisphere than low-anxious participants (de Pascalis & Morelli,
1990). Because smaller amplitude in response to the probes of the lexical recog-
nition task was assumed to reflect enhanced information processing, the high-
anxious participants can be inferred to have demonstrated more right-hemisphere
engagement on the task than did the low-anxious participants.
The fact that some studies have reported significant or near-significant in-
creases in activity for regions in both right and left hemispheres could reflect the
co-occurrence of both types of anxiety (e.g., Baxter et al., 1988; Fredrikson et
al., 1993; Reiman et al., 1989). Alternatively, the bilateral orbital frontal find-
ings reported by Baxter et al. for OCD patients might provide evidence for the
hypothesis that increased right anterior activity in anxious apprehension reflects
the presence of negative affect.
In two recent EEG studies, we directly tested the hypothesis of opposing pat-
terns of asymmetry for anxious apprehension and anxious arousal. Heller et al.
(1997a) selected participants on the basis of self-reported trait anxiety using the
STAI. We then manipulated anxious arousal on a within-subject basis by con-
trasting brain activity (EEG alpha) during rest periods to brain activity during a
Figure 12.1. Mean log EEG alpha voltage (+SE) for left and right midfrontal regions
for control (N = 19) and anxious (N = 19) groups averaged across the rest and listen pe-
riods of the fearful and sad narratives. Lower alpha values indicate greater brain activity.
(From Heller et al., 1997a).
task in which participants listened to emotional narratives designed to elicit anx-

ious arousal. As shown in Figure 12.1, anxious participants showed a larger
frontal asymmetry in favor of the left hemisphere than did controls across both
rest and listen periods. In contrast, when listening to the narratives, anxious par-
ticipants showed a selective increase in right parietal activity that was not demon-
strated by controls (Fig. 12.2).
The second study (Nitschke, 1998; Nitschke et al., 1999) employed a
between-subjects design to compare participants scoring high on a questionnaire
indexing anxious apprehension (Perm State Worry Questionnaire; Meyer et al.,
1990) to others scoring high on the Anxious Arousal scale of the Mood and Anx-
iety Symptom Questionnaire (Watson et al., 1995). Figure 12.3 shows the pat-
terns of hemispheric alpha asymmetry, with the anxious apprehension group
showing more left-sided and the anxious arousal group showing more right-sided
activity. Consistent with these findings, a recent ERP study also reported later-
alized effects for the two types of anxiety in a between-subject design using dif-
ferent self-report measures (Dien, 1999). These studies provide further evidence
for the utility of the distinction between anxious apprehension and anxious arousal
in efforts to elucidate the neurophysiological mechanisms involved in anxiety
and anxiety disorders.
An important consideration for any research on anxiety is the frequent co-
morbidity with depression. Despite this comorbidity, research has shown that
brain function in anxiety differs substantially from brain function in depression
Figure 12.2. Mean log EEG alpha voltage (+SE) for left and right parietal regions for
control (N = 19) and anxious (N = 19) groups during the rest and listen periods, aver-
aged across fearful and sad narratives. Lower alpha values indicate greater brain activity.
RP = right parietal; LP = left parietal. (From Heller et al., 1997a).
(for reviews, see Davidson et al., 1999; Heller & Nitschke, 1998). Although the
finding of more right than left activity in anterior cortical regions for anxious
arousal has also been reported for depression (e.g., Henriques & Davidson, 1991),
the increased left-hemisphere activity reported for anxious apprehension and the
increased right posterior activity associated with anxious arousal have not been
found for depression. Indeed, other commonly reported findings for depression
are in the opposite direction: decreased left anterior activity (e.g., George et al.,
1994) and decreased right posterior activity (e.g., Post et al., 1987). In addition,
several studies have reported bilateral decreases for anterior cortical regions in
depression (e.g., Bench et al., 1992), a finding that has not emerged in the anx-
iety literature.1 Although the differing patterns of brain activity reported for anx-
iety and for depression warrant the careful measurement of depression in stud-
ies examining anxiety, the EEG and hemodynamic findings distinguishing
anxious apprehension from anxious arousal cannot be accounted for by comor-
bid depression.
Behavioral Paradigms
Complementing tests of our hypotheses using biological measures, regional brain
activity can also be inferred from performance on tasks that depend on particu-
'Martinot et al. (1990) reported a bilateral decrease in prefrontal regions for OCD patients; how-
ever, despite not meeting criteria for DSM-III current major depressive episode, these patients may
still have been characterized by significantly higher levels of depression than the nonpatient controls.
Figure 12.3. Mean log EEG alpha power (+SE) for left and right hemispheres (averaged
across lateral frontal and parietal sites) for anxious apprehension (N = 9) and anxious
arousal (N — 19) groups. Lower alpha values indicate greater brain activity. (From
Nitschke et al., 1999).
lar brain regions. When samples of trait-anxious people are studied in the ab-
sence of experimental manipulations that might induce anxious arousal, results
are typically consistent with the increased left-hemisphere activity hypothesized
for anxious apprehension. Tucker et al. (1978) found that high-anxious subjects,
as classified by the trait scale of the STAI, tended to report right-ear tones as
louder and displayed a reduction in left lateral eye movements. Similarly, Tyler
and Tucker (1982) found that high-anxious individuals tended to use a process-
ing strategy characteristic of the left hemisphere, whereas low-anxious individ-
uals were more likely to use a strategy characteristic of the right hemisphere.
In contrast, when experimental conditions involve an immediate anxiety-
producing component, stimuli that can be interpreted as threatening, or stressful
life circumstances, the data are consistent with the increased right-hemisphere
activity predicted for anxious arousal. On a free-vision task of face process-
ing (Chimeric Faces Task [CFT]; Levy et al., 1983) that typically elicits a left-
hemispatial bias suggesting greater right posterior activity, Heller, Etienne, and
Miller (1995) found that participants scoring high on the trait version of the STAI
had larger left hemispatial (right-hemisphere) biases than those scoring low. This
pattern was replicated in a population of major depressed subjects and in a non-
clinical student population selected on the basis of recently developed anxiety
and depression scales (Keller et al., 2000). Importantly, for the latter two sam-
ples, the relationship between anxiety and the CFT only emerged after the vari-
ance associated with depression was removed. This set of findings suggests that
the strangeness and ambiguity of the CFT stimuli may lead to enhanced right-
hemisphere processing in trait-anxious people (see discussion of lesion studies
and anxiety below).
This interpretation is consistent with divided-visual-field studies demonstrat-
ing selective priming of the right hemisphere in response to threatening stimuli.
In a series of studies, Van Strien and colleagues reported improved left-visual-
field (right-hemisphere) performance on left-hemisphere tasks when threatening
words were presented concurrently (see Van Strien & Heijt, 1995; Van Strien &
Morpurgo, 1992).
Similar effects on right-hemisphere processing have been obtained under stress
conditions. Gruzelier and Phelan (1991) tested medical students on a divided-
visual-field lexical task under two conditions: 1 or 2 days before an examination
and 4 weeks before or after the examination. They found that the left-hemisphere
advantage in the nonstress condition gave way to a right-hemisphere advantage
in the stress condition. Similarly, Asbjornsen, Hugdahl, and Bryden (1992) found
that the threat of electric shock eliminated the left-hemisphere advantage for a
dichotic listening task.
Further support for our hypothesis of greater right-hemisphere activity in
anxious arousal is provided by work conducted by Tucker and colleagues. In
a study examining contralateral eye movements, Tucker et al. (1977) found sig-
nificantly more left than right lateral eye movements during an anxiety-
provoking task, suggesting greater right-hemisphere than left-hemisphere acti-
vation. These results were supported in a subsequent study in which an anxi-
ety-producing experimental condition was associated with a reversal of the typ-
ical left-hemisphere superiority on a verbal task (Tucker et al., 1978). More
recently, Johanson et al. (1998) found that spider phobics, a population pri-
marily characterized by anxious arousal, performed significantly better on right-
hemisphere than left-hemisphere tasks for a neuropsychological test battery.
Taken together, the behavioral neuropsychology findings presented here are
consistent with the hemodynamic and EEC studies reviewed above reporting
greater left-hemisphere activity in anxious apprehension and greater right-
hemisphere activity in anxious arousal.
LESION STUDIES AND ANXIETY
Complementing the EEC, hemodynamic, and behavioral paradigms often used

in neuropsychological research, another common strategy for investigating the
neuroanatomical bases of various functions is to examine the effects of brain
damage on particular behaviors. This approach has been quite helpful in fur-
thering our understanding of depression, which has been shown to be associated
principally with lesions in the left frontal lobe (see Robinson & Manes, Chapter
10, this volume).
Unfortunately, lesion studies have not systematically examined anxiety, much
less considered the distinction between anxious apprehension and anxious
arousal. Furthermore, early stages of recovery from traumatic brain injury are of-
ten characterized by emotional disturbances, such as agitation, irritability, and
emotional volatility, that make it difficult to assess the presence and region-
specific impact of anxiety. Common sense would predict that anxiety would be
a typical psychological response to the trauma of physical disability, illness, and
accompanying life changes; however, in some cases, anxiety is notably absent.
In fact, important inferences about the neuropsychology of anxiety can be drawn
from those people in whom anxiety and emotional distress are not present.
Early descriptions of dramatically different emotional reactions after left ver-
sus right brain damage were systematically studied by Gainotti (1972) and later
by Robinson and colleagues (e.g., Starkstein & Robinson, 1988). Left brain dam-
age, particularly frontal, is associated with a "catastrophic" emotional propen-
sity, marked by tearfulness, distress, and agitation. Right brain damage, in con-
trast, is more often accompanied by indifference, euphoria, or apathy, indicating
a remarkable and inappropriate lack of anxiety. Research examining behavior af-
ter unilateral sodium amobarbital injection in populations without brain damage
has provided almost identical findings (e.g., Ahern et al., 1994; Lee et al., 1990).
In addition, attentional abnormalities (e.g., hemineglect, when patients ignore
stimuli on the left side of space) and anosagnosia (when patients deny or mini-
mize the existence of an illness or disability) are also often present in patients
with right-hemisphere lesions. McGlynn and Schacter (1989) described a typi-
cal case of unawareness and indifference in a head-injured patient who had been
a practicing physician before an automobile accident: "Shortly after regaining
consciousness he insisted that he could soon return home and he began to make
implausible plans for the future. ... He confabulated about the cause of his ill-
ness ... and exhibited no anxiety about his condition" (p. 170). The lack of anx-
iety in people with decreased right-hemisphere function due to a lesion parallels
findings of increased right-hemisphere activity in anxious arousal.
Although the neuroanatomical damage is somewhat varied in the populations
that have been studied, there is general agreement that the indifference reaction
is most often reported after damage to right parietal regions (McGlynn & Schac-
ter, 1989). This area has been shown to be differentially involved in processing
emotional information, especially negative material (e.g., Borod et al., 1992;
Heller & Levy, 1981), in spatial attention (e.g., Heilman, Watson, & Valenstein,
1985; Mesulam, 1981; see also Heller, 1993), and in monitoring responses to ex-
ternal sensory stimuli (e.g., Heilman & Van den Abell, 1979; Pardo, Fox, &
Raichle, 1991). In addition, this and other right-hemisphere regions have been
3 I0 EMOTIONAL DISORDERS
found to be uniquely involved in modulation and regulation of autonomic, cor-

tical, and self-reported arousal (for reviews, see Heller, 1993; Heller et al., 1997b;
Wittling, 1995), in the perception and integration of multimodal sensory inte-
gration (Goldberg & Costa, 1981), and in understanding the way in which ob-
jects and events are related to each other in a real-world context (Heller, 1994).
Apropos of these observations, Bear (1986) referred to the right hemisphere as
selectively engaged in "emotional surveillance."
Taken together, these results led Heller (1993) to describe a similar system
confined to the right temporoparietal region "whose properties encompass the
cognitive, attentional, and physiological attributes that would be useful for opti-
mal efficiency in responding to environmental events" (pp. 480—481). This view
is consistent with data described earlier suggesting that the right hemisphere is
primed by material that could be interpreted as threatening (e.g., negative words,
ambiguous stimuli) and with evidence that increased activity in this region ac-
companies anxious arousal. The absence of anxiety in patients with right pari-
etal brain damage may be a manifestation of dysfunction in a broader network
that not only governs withdrawal and avoidance behaviors (Davidson, 1992,
1998) but also attends to the external environment on an ongoing basis, moni-
tors it for threat, orients toward potential threat, appraises the context for infor-
mation regarding the possibility of threat, and exerts hierarchical control over the
autonomic and somatic functions for responding to threat. That the cognitive bi-
ases typically found in anxiety appear to reflect the engagement of this right-
hemisphere system is discussed in the next section.
COGNITIVE STUDIES OF ANXIETY
Cognitive Biases
As neuropsychological research on anxiety has matured during the 1980s and

1990s, an additional line of investigation has substantially advanced our knowl-
edge about the cognitive concomitants of anxiety. There have been numerous re-
ports of an attentional bias to threat in trait anxiety and the various anxiety dis-
orders (for reviews, see Eysenck, 1992; Mathews & MacLeod, 1994; McNally,
1998), with some studies not finding effects unless state anxiety was induced
(e.g., Broadbent & Broadbent, 1988; MacLeod, 1990; MacLeod & Mathews,
1988). This bias has emerged for subliminal as well as for supraliminal stimuli,
suggesting that automatic, preattentive processing is involved (e.g., Bradley et
al., 1995; MacLeod & Hagan, 1992; MacLeod & Rutherford, 1992; Mogg et al.,
1993). Furthermore, attentional biases have been found to disappear in GAD pa-
tients, social phobics, spider phobics, and rape victims with post-traumatic stress
Anxiety, Stress, and Cortical Brain Function 31 I
disorder on remission (for review, see McNally, 1998), suggesting that such bi-
ases are state dependent.
Cognitive biases are also present in anxiety in the form of interpretation bi-
ases. Across a number of different paradigms involving ambiguous stimuli that
can be interpreted as threatening or neutral, anxious people choose the threaten-
ing meaning. Similar to findings for attentional biases, the selective processing
of ambiguous information in anxious individuals is most consistently observed
in conditions eliciting state anxiety (e.g., MacLeod, 1990). Further evidence that
these biases are state dependent is provided by research showing that recovered
GAD patients do not exhibit the selective interpretation effect (Mathews,
Richards, & Eysenck, 1989b; Eysenck et al., 1991).
Our neuropsychological framework for anxiety suggests that these attentional
and interpretation biases are related to anxious arousal and to the emotion sur-
veillance system of the right hemisphere. As reviewed above, this region of the
brain has been shown to be primed by ambiguous and threatening stimuli and
hypothesized to play a role in orienting to such stimuli. In addition, populations
characterized by anxious arousal consistently show increased right-hemisphere
activity at rest (e.g., Reiman et al., 1984), suggesting that anxious arousal is as-
sociated with the engagement of the emotional surveillance system, even in the
absence of an emotional stimulus. This right-hemisphere system may correspond
to the cortical processes that McNally (1998) postulated to accompany a sub-
cortical circuit involved in attentional biases toward threat. Thus, anxious arousal
can be hypothesized to produce a set of behaviors that include attentional and
other cognitive responses designed to evaluate the presence of a threat.
In contrast to findings of attentional and interpretation biases in anxiety, re-
sults of studies examining explicit and implicit memory biases have been equiv-
ocal (for reviews, see Eysenck, 1992; Mathews & MacLeod, 1994; McNally,
1998). Previous work examining the neuropsychology of cognitive biases in de-
pression may inform attempts to understand why some studies find memory bi-
ases in anxiety whereas others do not. Heller and Nitschke (1997) suggested that
the negative memory bias reported so consistently in depression (for reviews, see
Gotlib, Gilboa, & Kaplan, 2000; Mathews & MacLeod, 1994) is associated with
more right than left cortical activity in anterior regions, the same pattern that
emerges in studies examining negative affect. Similarly, the greater right than
left anterior activity characterizing anxious arousal should be accompanied by a
negative memory bias, as has been found in panic disorder patients (e.g., Amir
et al., 1996a; Becker, Rinck, & Margraf, 1994; Cloitre et al., 1994) and post-
traumatic stress disorder patients (Amir et al., 1996b; Vrana, Roodman, & Beck-
ham, 1995). Conversely, many studies have found no memory biases in samples
characterized better by anxious apprehension than by anxious arousal (e.g.,
MacLeod & McLaughlin, 1995; Mathews et al., 1989a; Mogg, Mathews, & Wein-
man, 1987; Nugent & Mineka, 1994; Rapee et al., 1994; Watts & Coyle, 1993).
In sum, the neuropsychological perspective provided here can account for the
dissociation among the different cognitive biases (cf. Eysenck, 1992; Williams
et al., 1988).
Cognitive Impairments
An understanding of the neuropsychological mechanisms involved in anxiety may

inform other cognitive research on anxiety as well. Unlike depression, which is
accompanied by deficits in explicit memory, executive functions, and visuospa-
tial skills (for review, see Heller & Nitschke, 1997), results for anxiety have been
variable. Although numerous studies have reported impaired performance (par-
ticularly for trait-anxious people doing difficult tasks under stressful conditions
that elicit state anxiety), others have found no effects of anxiety (for review, see
Eysenck & Calvo, 1992). At times, high trait or state anxiety has even been as-
sociated with superior performance.
To explain these findings, Eysenck and Calvo (1992) argued that worry, or
anxious apprehension, affects performance negatively by pre-empting process-
ing and storage capacities of the working memory system. Working memory has
been theorized to be comprised of three general systems: a central executive, an
articulatory loop that involves verbal rehearsal and phonological storage, and a
*
visuospatial processor (Baddeley, 1986). Eysenck and Calvo (1992) theorized
that worry is particularly likely to disrupt the central processor and the articula-
tory loop.
This proposition is consistent with the neuropsychological data reviewed above
that suggest a special role of the left hemisphere in anxious apprehension. Cur-
rent research on the neural mechanisms associated with working memory sug-
gests that dorsolateral prefrontal cortex is associated with the "central proces-
sor," that Broca's area in the left anterior region is associated with the rehearsal
component of the articulatory loop, and that left posterior areas around the an-
gular and supramarginal gyrus are associated with the phonological storage com-
ponent of the articulatory loop (for review, see Gupta & MacWhinney, 1997).
Cortical activity associated with apprehensive thoughts might thus interfere with
information processing of other tasks in both anterior and posterior regions of
the left hemisphere: the greater the level of worry, the greater the interference.
Furthermore, it follows that performance would most likely be impaired on tasks
that impose considerable demands on these components of the working memory
system (Eysenck & Calvo, 1992).
Using our neuropsychological framework for anxious apprehension and anx-
ious arousal as a guide, we have speculated about the brain regions involved in
cognitive abnormalities accompanying anxiety. With the advancing sophistica-
tion of hemodynamic and electrophysiological imaging techniques, the time is
ripe for research paradigms that can investigate simultaneously the specific cog-
nitive characteristics and the patterns of regional brain activity associated with
anxiety.
Considering a number of conceptualizations of anxiety, we argued for the util-

ity of a distinction between anxious apprehension and anxious arousal. Like anx-
iety, stress is not a unitary construct, and understanding the relationships between
external stressors and psychological stress is critical for research on anxiety. At
the level of the cortex, we suspect a major role for left-hemisphere functions in
anxious apprehension and for right-hemisphere functions in anxious arousal.
Electrophysiological and hemodynamic studies have provided remarkably con-
sistent evidence for our position that anxious apprehension is associated with
more left-sided activity and anxious arousal with more right-sided activity. In ad-
dition, the utility of distinguishing the two types of anxiety is apparent when in-
terpreting results for performance on left-hemisphere and right-hemisphere be-
havioral tasks. Corroborating evidence for the neuropsychological perspective
espoused in this chapter has also been obtained from lesion studies and cogni-
tive research.
In sum, the distinction between anxious apprehension and anxious arousal can
resolve many of the inconsistencies that have emerged for the wide range of em-
pirical approaches used in investigations of anxiety. Continued research is likely
to provide greater specificity for the psychological and neurophysiological
processes and anatomic regions involved in anxiety. To elucidate the mechanisms
critical for each type of anxiety, the extensive animal research implicating vari-
ous subcortical areas in fear and the increasing accuracy in hemodynamic imag-
ing of the subcortex could contribute monumentally to the human work reviewed
in this chapter primarily focused on cortical brain function.
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13
Violence Associated with Anger and Impulsivity
ANGELA SCARPA AND ADRIAN RAINE
According to the Uniform Crime Report, violent crime in the United States rose
by 81% in the two decades between 1973 and 1992, and the largest increase was
in aggravated assault (Stanton, Baldwin, & Rachuba, 1997). In view of the per-
vasiveness of violence and the tragic consequences it has on individuals and so-
ciety, it is important to understand the factors that initiate and maintain the propen-
sity to behave violently. In this context, anger and impulsivity become pivotal
issues in the study of violence.
Paralleling the typologies of defensive and predatory aggression in the animal
literature, human aggression has been primarily grouped into impulsive-emo-
tional or controlled-instrumental subtypes (Vitiello & Stoff, 1997). Impulsive-
emotional violence occurs suddenly, without forethought, and in response to some
perceived threat, provocation, or insult, within the context of associated anger,
high emotionality, and high impulsivity (Berkowitz, 1993). It may incorporate
acts such as child physical abuse, assault, and murder/manslaughter, as well as
less serious forms of physical and/or verbal aggression (e.g., biting, kicking,
screaming). Controlled-instrumental violence involves a relatively nonemotional
display of aggression directed at obtaining some goal, usually within the context
of premeditation and manipulation. It may incorporate acts such as planned rob-
beries, arsons, and serial murders, among others. These two forms of aggression
have also been referred to in the literature as reactive versus proactive (Dodgezyxwvuts
& Coie, 1987) and affective/defensive versus predatory (Moyer, 1976).
320
Violence Associated with Anger and Impulsivrty 321
The validity of these two types of aggressive behavior has been initially sup-
ported by several studies that show distinct differences among children and ado-
lescents whose aggressive/violent behavior was classified as primarily impulsive-
emotional or controlled-instrumental. According to these studies, youth with
impulsive-emotional aggression (termed either affective or reactive aggression)
tended to have an earlier age of onset of behavior problems, more stressful life
events, a greater likelihood of comorbid psychiatric disorder or concurrent ad-
justment difficulties, and deficits in early stages of social information process-
ing (Dodge & Coie, 1987; Dodge et al., 1997; Vitiello et al., 1990).
Along with these social, emotional, and cognitive differences, it is plausible
that neurobiological variables also differentiate the two aggressive types. Impul-
sive-emotional aggression, in particular, may have biological correlates tied to
its strong association with anger, impulsivity, or emotional disorders. Animal
studies also have indicated distinct biological profiles between defensive and
predatory aggression, as reviewed by Eichelman (1995), Reis (1974), and Vi-
tiello and Stoff (1997). For example, defensive forms of animal aggression have
been associated with intense autonomic activation, stimulation of the ventrome-
dial hypothalamus, decreased serotonergic activity, and increased noradrenergic
and dopaminergic activity. Predatory forms, on the other hand, have been asso-
ciated with little autonomic activation, lesions of the frontomedial hypothalamus,
lesions of the orbital prefrontal cortex, and increased cholinergic activity.
Few studies of biological bases of antisocial behavior in humans have catego-
rized aggression or violence according to these subtypes. The purpose of this chap-
ter is to review biological findings on crime and violence and then determine what
can be concluded about the underpinnings of impulsive-emotional aggression based
on these findings. The focus on biological findings does not preclude the clearly
important role of social/environmental and psychological contributors to violence,
but rather highlights one growing body of literature that may aid in a more com-
plete understanding of emotionally violent behavior. This includes findings in neu-
ropsychology (i.e., testing, brain lesions, and brain imaging studies) and related ar-
eas of neurochemistry, hormones, and psychophysiology.
FRAMEWORK
Previously, we have suggested that emotional aggression is related to "1) a pre-

disposition to experience negative affect and arousal, 2) the inability to regulate
or soothe negative affect or arousal, and 3) thought processes that will increase
the likelihood of experiencing anger or making a decision to aggress" (Scarpa &
Raine, 1997, p. 385). We further argued that biologic contributions could influ-
ence any of these risk factors and that the effect would be most pronounced when
individuals were faced with stressful environments where emotional arousal and
negative affect would be peaked. With these criteria, biological findings can be
evaluated regarding their relationship to impulsive-emotional aggression.
The general theoretical framework of this chapter, then, is that a pattern
of neurobiological influences is associated with each of the risk factors for
impulsive-emotional aggression named above. Regarding the first two risks, neg-
ative affect (including depression, anxiety, and hostility), physiological arousal,
and the inability to regulate affect and arousal have been ascribed to greater right
cerebral activation, particularly in the frontotemporal regions (Cechetto & Saper,
1990; Demaree & Harrison, 1997; see also, Nitschke, Heller, & Miller, Chapter
12, this volume). Regarding the third risk, frontotemporal limbic dysfunction is
related to impaired executive cognitive functioning, which encompasses abilities
such as attention, planning, organization, abstract reasoning, self-monitoring, and
the ability to use feedback to modulate behavior (Foster, Eskes, & Stuss, 1994;
Wallace, Bachorowski, & Newman, 1991). This has been speculated to lead to
cognitive biases that increase the chances of behaving aggressively in response
to stressful and provocative situations (Giancola, 1995).
NEUROPSYCHOLOGY
Three areas of the brain have been most consistently described as related to the
manifestation or inhibition of aggression: (1) the brain stem and hypothalamus,
(2) the limbic system (including temporal cortex), and (3) the frontal cortex. Each
of these three areas are interrelated in that components of the limbic system pro-
ject to the hypothalamus, and the frontal cortex functions in modulating limbic
and hypothalamic output. In general, neuropsychological findings about violence
from studies using standardized tests, brain lesions in animals and humans, and
brain imaging implicate frontal and temporal dysfunction.
Neuropsychological Tests
Anterior/frontal dysfunction in violent adult criminals has been implicated in neu-

ropsychological studies with the Halstead-Reitan Neuropsychological Test Battery
(Flor-Henry, 1973; Yeudall & Fromm-Auch, 1979) and the Luria-Nebraska Neu-
ropsychological Battery (Bryant et al., 1984). Further support comes from a prospec-
tive study of 10-12-year-old boys with and without a paternal history of substance
abuse. A composite score from five neuropsychological tests was used to measure
impaired executive cognitive ability thought to reflect mild prefrontal dysfunction.
Impaired executive cognitive functioning predicted reactive aggression 2 years later
in the boys at high risk for substance abuse (Giancola et al., 1996). Reactive aggres-
sion was defined as an impulsive hostile reaction to frustration that is committed with-
out forethought, closely resembling the impulsive-emotional form of aggression.
Violence Associated with Anger and Impulsivity 323
Others have suggested that brain dysfunction in criminals involves disruption

to both frontal and temporal corticolimbic (i.e., hippocampal/amygdala) systems,
localized to the left hemisphere (Flor-Henry, 1973; Yeudall & Fromm-Auch,
1979). Left hemisphere deficits in aggressive individuals are consistent with stud-
ies showing increased negative affect and arousal associated with relative activa-
tion of the right hemisphere (Nitschke, Heller, & Miller, Chapter 12, this volume).
Brain Lesion Studies
Multisite brain dysfunction, with particular focus on limbic system sites involv-
ing temporal and frontal projections, is also supported by lesion studies in ani-
mals and humans. Lesion studies in animals involve the ablation of localized
brain sites and implicate the amygdala and prefrontal cortex in violence (Gian-
cola, 1995; Siegel & Mirsky, 1990). Lesion studies in humans are generally less
localized, as they involve brain trauma resulting from head injury, surgery, or
epileptic seizures. Aggression is decreased, however, in patients with amyg-
dalectomy (O'Callaghan & Carroll, 1982). Also, patients with known frontal lobe
damage have shown a pattern of personality changes including impulsivity, ar-
gumentativeness, lack of concern for consequences of behavior, loss of social
graces, distractibility, shallowness, lability, violence, and reduced ability to uti-
lize symbols (termed frontal lobe syndrome) (Silver & Yudofsky, 1987).
The relationship between temporal lobe dysfunction and violence also has been
studied in individuals with temporal lobe epilepsy (see Heilman et al., Chapter
15, this volume). Historically, it was believed that violent episodes may occur
during (ictal), immediately after (postictal), or between (interictal) seizures, ei-
ther as a direct result of brain stimulation or consequent to the confusion and dis-
organization following seizures. In a recent review of these studies, Volavka
(1995) concluded that (7) seizure-related violence in epileptics is extremely rare;
(2) although prisoners have a higher rate of seizure disorders relative to the gen-
eral population, those without seizure disorders are equally as violent as those
with seizure disorders; and (3) these studies have identified the same risk factors
for violence that have been found in nonepileptic populations (i.e., young age,
male gender, low IQ, low socioeconomic status, and adverse rearing environ-
ment). As such, effects of temporal lobe dysfunction secondary to seizure activ-
ity seem trivial, but these studies do not address whether nonseizure temporal
lobe dysfunction increases violence.
Brain Imaging Studies
Recent reviews of brain imaging findings on violence support the neuropsycho-

logical findings of frontal and temporal deficits (Henry & Moffitt, 1997; Raine,
1993). Most of the structural studies with magnetic resonance imaging (MRI)
and computerized tomography (CT) have implicated damage to the temporal lobe,
whereas functional studies with single photon emission computerized tomogra-
phy (SPECT) and positron emission tomography (PET) have found both tempo-
ral and frontal deficits.
Five of six recent analyses of antisocial/violent offenders not contained in the
above reviews have also observed reduced frontal or temporal functioning in vio-
lent psychiatric patients (frontal and temporal deficits; Volkow et al., 1995), alco-
holics with antisocial personality disorder (frontal deficits; Kuruoglu et al., 1996),
violent offenders supsected of organic brain disease (temporal deficits; Seidenwurm
et al., 1997), and murderers pleading not guilty by reason of insanity (frontal and
temporal deficits; Raine, Buchsbaum, & La Casse, 1997; Raine et al., 1998a). In-
terestingly, one additional study showed increased functioning of the frontotem-
poral regions in drug-abusing psychopaths (Intrator et al., 1997). It is likely that
discrepant findings may be a function of the different subject groups, types of vi-
olence, and experimental methods used in the various studies (Volkow et al., 1995).
The brain imaging studies by Raine et al. (1997, 1998a) are of special interest
because they overcome some of the earlier methodological flaws in design. Frontal
lobe glucose metabolism was assessed with PET in 41 murderers pleading not
guilty by reason of insanity compared with 41 controls matched by age, sex, and
presence/absence of schizophrenia. All participants with a history of seizure dis-
order, head trauma, or substance abuse were excluded. Murderers in this study
failed to show the prefrontal activation observable in controls during a continu-
ous performance task that is specifically designed to elicit such activation.
In addition to prefrontal deficits, significantly reduced glucose metabolism was
also observed in the corpus callosum, superior parietal gyrus, and left angular
gyrus, and left hemisphere deficits were found in the amygdala, thalamus, and
medial temporal lobe. It was speculated by Raine, Buchsbaum, and La Casse
(1997) that reduced functioning of the corpus callosum might result in a relative
inability of the left hemisphere to control and regulate the more "emotional" right
hemisphere.
In a recent reanalysis of the above data (Raine et al., 1998a), murderers were
divided into those whose murders were planned, instrumental, and predatory in
nature and those whose attacks were relatively impulsive, unplanned, and char-
acterized by a high degree of emotional reactivity preceded by arguments. Re-
sults indicated that it was specifically the emotionally reactive murderers who
were characterized by significant prefrontal dysfunction, whereas predatory mur-
derers had levels of prefrontal glucose metabolism similar to controls. Raine
(1993) speculated that, because the prefrontal cortex is involved in planning, reg-
ulating, and controlling behavior, those who plan their murders must have a rea-
sonably functional prefrontal cortex. Conversely, those whose murders are im-
pulsive and lacking in behavioral control are most likely to be lacking the
regulatory influence of a functional prefrontal cortex.
Summary of Neuropsychological Findings
As is typical of most biological studies of violence, few studies examined sepa-

rate effects for the form of violent behavior. There is some evidence to suggest,
however, that frontal dysfunction is predominantly related to impulsive-emotional
forms of aggression. First, a study with neuropsychological tests suggested that
mild prefrontal dysfunction was predictive of reactive aggression in children (Gi-
ancola et al., 1996). Second, studies examining damage to the frontal cortex in
noncriminal samples have shown a pattern of emotional and impulsive changes
that has come to be called frontal lobe syndrome (Silver & Yudofsky, 1987).
Third, the brain imaging findings suggest reduced prefrontal activation specifi-
cally in murderers whose crime was impulsive rather than instrumental (Raine
et al., 1998a). Fourth, the frontal cortex has projections to the temporal lobe, lim-
bic system, and hypothalamus, all of which are involved in the regulation and
expression of emotion (Weiger & Bear, 1988).
Finally, if risk for impulsive-emotional aggression is highest when dysregula-
tion of negative affect and arousal is peaked by environmental provocation, as
suggested by Scarpa and Raine (1997), then aggression should increase when
prefrontal dysfunction is combined with an adverse environment. In contrast to
this suggestion, Raine et al. (1998b) found greater reductions in prefrontal func-
tioning in murderers from benign home backgrounds relative to those from de-
prived backgrounds or to noncriminal controls. In a sample of juvenile delin-
quents, however, the highest rates of violence were found for those having a
combination of neuropsychological impairment and a history of physical abuse
or family violence (Lewis et al., 1989). This combination of emotional lability,
impulsivity, and stressful experiences in violent individuals with frontal (or pos-
sibly frontotemporal limbic) dysfunction is consistent with impulsive-emotional
aggression. The results of Raine et al. (1998b) need to be replicated, but they do
suggest the intriguing possibility that frontal dysfunction itself can lead to dis-
inhibited violent behavior in the absence of a "social push" for that behavior.
NEUROCHEMISTRY
A meta-analysis of 29 studies published before 1992, which examined neuro-

transmitter substances in antisocial children and adults, indicated overall effects
for decreased metabolites of serotonin and norepinephrine in cerebrospinal fluid
(CSF), and no effect for dopamine in antisocial individuals (Scerbo & Raine,
1993). These results were particularly moderated by the presence of alcohol abuse
or affective instability. Indications of reduced CSF serotonin were found in all
antisocial groups but were even more marked in suicide attempters and nonal-
coholics. Indications of reduced CSF norepinephrine, however, were only found
in antisocial samples who also had diagnoses of alcohol abuse, borderline per-
sonality disorder, depression, or dysthymia.
The relationship found between CSF noradrenergic activity and affective in-
stability in violent samples is consistent with findings indicating increased like-
lihood of psychiatric disorder and emotion regulatory problems in individuals
with impulsive-emotional aggression (Dodge et al., 1997; Vitiello et al., 1990).
These findings suggest that reductions in serotonergic activity may underlie a
general propensity to aggress, whereas the addition of a central norepinephrine
disturbance may be related to impulsive-emotional aggression.
The idea that central norepinephrine mediates the affective instability associ-
ated with impulsive-emotional aggression is also consistent with frontotemporal
limbic dysfunction. The primary source of central norepinephrine (i.e., the locus
ceruleus) has projections to the hypothalamus through the median forebrain bun-
dle. The hypothalamus, in turn, is densely interconnected with the limbic system
and has both frontal and temporal cortical connections. These interconnections
may comprise the neural substrate by which norepinephrine affects emotion and
emotional expressivity. Together with a serotonergic-mediated propensity to
aggress, such dysregulation of negative affect might increase the likelihood of
impulsive-emotional aggression.
HORMONES
Although the release of hormones is also governed by the hypothalamus, the mo-
tivational and behavioral effects of different hormones seem to vary. The vary-
ing effects may serve to fine tune brain-behavior responses to emotions and to
the environment. Studies on hormonal relationships to violence have generally
examined testosterone, cortisol, and hypoglycemia. Testosterone production is
regulated through the hypothalamic-pituitary-gonadal axis, cortisol production
through the hypothalamic-pituitary-adrenal (HPA) axis, and hypoglycemia
through the direct hypothalamic innervation of the sympathetic nervous system.
Testosterone
Overall, studies of testosterone and aggression have shown a positive associa-

tion. Studies correlating testosterone with questionnaire measures of aggression
in the general population have generally produced weak or nonsignificant find-
ings, whereas studies of violent incarcerated inmates have more consistently pro-
duced results of moderate to large strength (for review, see Archer, 1991). Find-
ings of increased testosterone in aggressive clinically referred children and young
adults have been less consistent (Constantino et al., 1993; Dabbs, Jurkovic, &
Frady, 1991; Scerbo & Kolko, 1994).
Most of these studies did not differentiate types of aggression or violence. Ol-
weus et al. (1988), however, reported increased testosterone in male adolescents
who self-reported high levels of both provoked (reactive) and unprovoked (proac-
tive) aggressive behavior. One of the few studies of females also reported ele-
vated testosterone levels in prisoners whose current offense was an unprovoked
violent crime but not in those whose crime was defensive (i.e., violence in re-
action to physical assault) (Dabbs et al., 1988). Others have found testosterone
to be positively related to social dominance and status in prisoners (Ehrenkranz,
Bliss, & Sheard, 1974) and competitive success (Mazur & Lamb, 1980). Alto-
gether, these results suggest that the relationship of testosterone to violence may
be primarily related to goal achievement found in controlled-instrumental ag-
gression rather than to reactivity found in impulsive-emotional aggression.
Cortisol
Cortisol is a stress hormone released through HPA activation. Cortisol levels

have been reported to be reduced in habitually violent offenders (Virkkunen,
1985), in aggressive schoolchildren (Tennes & Kreye, 1985), and in children and
adolescents with conduct problems (Lahey & McBurnett, 1992; Susman, Dorn,
& Chrousos, 1991), suggestive of possible low HPA activation or anxiety in these
individuals. These results have not been consistently found, however, and corti-
sol effects may be moderated by other variables such as alcohol, comorbid anx-
iety, or environmental experiences. Buy dens and Branchey (1992), for example,
found that increased levels of cortisol characterized violent alcoholics. McBur-
nett et al. (1991) found elevated cortisol levels in conduct disordered children
with comorbid anxiety disorder. Also, Scarpa (1997) reported that increased cor-
tisol reactivity during a stressor interacted with physical abuse history to heighten
the risk of aggression in clinically referred children with disruptive behavior dis-
orders. Finally, in a study examining testosterone and cortisol in a group of dis-
ruptive children, resting levels of both hormones were positively associated with
antisocial behavior problems, but cortisol was also positively related to internal-
izing (i.e., emotional) behavior problems and impulsivity (A. Scarpa & D.J.
Kolko, unpublished data, 1996). These latter studies indicating a relationship be-
tween heightened cortisol level/reactivity in antisocial individuals with alco-
holism, comorbid emotional problems, and impulsivity are consistent with
impulsive-emotional aggression.
Hypoglycemia
Hypoglycemia is a blood sugar deficiency caused by an overproduction of in-

sulin secreted by the pancreas. Hypoglycemia (or low blood sugar levels) may
elicit irritability, aggression, confusion, amnesia, seizures, and eventually un-
consciousness. A number of studies have linked hypoglycemia to violent and ag-

gressive behavior, particularly in individuals with a history of alcohol abuse
(Virkkunen, 1986; Virkkunen et al., 1989). These findings are qualified by the
fact that, to date, there is no clear evidence indicating that violent offenders are
hypoglycemic at the time of their violent offense (Kanarek, 1990).
Interestingly, hypoglycemia can occur as an indirect effect of cortisol over-
production. HPA-stimulated increases in cortisol lead to a rise in blood sugar,
and, as part of a negative feedback loop, pancreatic glucogen is inhibited. Gluco-
gen normally suppresses insulin, and so its reduction leads to insulin overpro-
duction and a consequent drop in blood sugar level. In view of the relationship
between hypoglycemia and negative affect and possibly with HPA arousal, hy-
poglycemia-related violence seems most closely linked to the impulsive-
emotional form.
PSYCHOPHYSIOLOGY
The most commonly used psychophysiological measures recorded from antiso-

cial populations have been skin conductance (SC), heart rate (HR), and cortical
measures of electroencephalogram (EEG) and event-related potentials (ERP). Au-
tonomic nervous system (ANS) activity produces SC through sympathetic me-
diation and HR through both sympathetic and parasympathetic mediation. Many
of the ANS neurons exist in the brain and spinal cord and require input from the
cortex, brain stem, hypothalamus, and spinal cord. In addition to brain stem in-
fluences, there is evidence to suggest that the frontal and temporal lobes are
involved in the regulation of SC and HR (Heilman, Bowers, & Valenstein,
1993; Hugdahl et al., 1983; Nitschke, Heller, & Miller, Chapter 12, this volume;
Raine, Reynolds, & Sheard, 1991). Reviews of psychophysiological studies and
impulsive-emotional aggression have been recently published (Scarpa & Raine,
1997). These reviews are summarized here.
Skin Conductance
Reviews of SC studies indicate that (1) there is some evidence for SC under-
arousal in antisocial individuals, particularly with respect to nonviolent forms of
crime; (2) SC-orienting deficits seem specific to antisocial individuals with con-
comitant schizotypal or schizoid features; (3) the findings up to 1978 of reduced
SC responsivity to aversive stimuli in psychopaths generally have not been ob-
served in more recent studies in either psychopathic or nonpsychopathic antiso-
cial populations; and (4) the strongest findings support reduced SC classical con-
ditioning and longer SC half-recovery times in antisocial populations. Reduced
classical conditioning has been interpreted as reflecting a poorer ability to form
conditioned emotional responses to potentially punitive situations, resulting in

poor conscience development and antisocial behavior (Eysenck, 1977). Slower
recovery rates imply slower dissipation of autonomic activation, possibly indi-
cating slower recovery from an emotional fear state (Mednick, 1977).
In general, these results have been found in populations with primarily non-
violent forms of crime or in samples in which type of antisocial behavior was
not distinguished (e.g., psychopathic populations). Only one of the reviewed SC
arousal studies compared types of crime and found that underarousal character-
ized crimes of evasion (e.g., customs offenses) but not other forms of crime
(Buikhuisen et al., 1985). Interestingly, the one SC responsivity study that specif-
ically identified individuals characterized by affective violence showed larger
SC responses to verbal stimuli in the violent group (Lakosina & Trunova, 1985).
Finally, although not distinguished by type of antisocial behavior, several SC
conditioning studies found poorer classical conditioning in only those antisocial
individuals from high social class backgrounds (Raine & Venables, 1981) or good
homes (Hemming, 1981). Thus, the overall SC findings of underarousal, response
deficits, and poor conditioning do not seem to characterize impulsive-emotional
aggression but rather relate to nonviolent forms of antisocial behavior.
Heart Rate
In terms of HR, studies of institutionalized adult offenders show no differences

in resting HR. In contrast, all studies conducted to date on younger and pre-
dominantly noninstitutionalized or nonclinical populations show reduced resting
HR levels in antisocial people (for review, see Raine, 1993). Reduced HR may
reflect autonomic underarousal (Raine, Venables, & Williams, 1990a) or, alter-
natively, fearlessness to novel situations (Kagan, 1989; Venables, 1987).
Of two studies that examined violent behavior, both found the lowest resting
HR levels in persons exhibiting violent behavior (Farrington, 1987; Wadsworth,
1976), but they did not specify types of violence. Only one known study distin-
guished form of aggression (Pitts, 1993). In that study, lower resting HR levels
were exhibited in both proactive (i.e., controlled) and reactive (i.e., impulsive)
aggressive schoolboys relative to nonaggressive controls. Interestingly, only the
reactive subtype showed an increase in HR after a simulated provocation. These
results are also consistent with a series of laboratory aggression studies by Zill-
mann and colleagues, which indicated that autonomic arousal facilitates aggres-
sive behavior, particularly when participants were previously provoked and when
the provocation was perceived as intentional or deliberate (for review, see Zill-
mann, 1983). With the exception of Farrington (1987) and Wadsworth (1976),
these studies indicate HR underarousal in young, noninstitutionalized populations
displaying mild levels of aggression or antisocial behavior and suggest that HR
reactivity characterizes impulsive-emotional forms of aggression.
Electroencephalogram
Cortical EEG studies indicate that abnormalities exist in resting EEG in criminal
populations, particularly violent recidivistic offending (Mednick et al., 1982), with
the predominant deficit being excessive slow wave activity, particularly in the
frontal cortex. Two out of three studies that examined premeditated versus impul-
sive/motiveless violent crime found diffusely abnormal EEG in the criminals whose
offense was apparently without instrumental motive (Driver, West, & Faulk, 1974;
Hill & Pond, 1952; Okasha, Sadek, Moneim, 1975). These abnormalities are
thought to reflect either general underarousal (Raine, Venables, & Williams, 1990a)
or cortical immaturity (Hare, 1970). In a review of EEG studies, however, Volavka
(1995) suggested that the possibility of brain injury or cortical disinhibition, in ad-
dition to the hypotheses of underarousal and cortical immaturity, could not be ruled
out. These studies indicate that abnormal EEG findings in antisocial populations
may be related to impulsive-emotional forms of violence.
Event-Related Potentials
Cortical ERP studies generally indicate increased latencies in the early and mid-
dle components of ERP (i.e., brain stem auditory evoked potentials and N100)
and enhanced late-component P300 amplitudes to stimuli of interest in antisocial
samples. Raine (1993) has suggested that these processes may be conceptually
and causally linked such that the early components relate to excessive filtering
of stimuli and resulting underarousal that lead to sensation-seeking (related to
the N100 findings), which may partly account for enhanced attention (i.e., in-
creased P300) to events of interest. These ERP studies have primarily involved
psychopathic populations.
Studies of violent individuals, however, have generally found smaller P300
amplitudes than nonviolent controls (Barratt et al., 1997; Branchey, Buydens-
Branchey, & Lieber, 1988; Braverman, 1993; Gerstle, Mathias, & Stanford,
1988). Two of these studies included subjects who specifically displayed impul-
sive aggression (Barratt et al., 1997; Gerstle, Mathias, & Stanford, 1988). A re-
cent study has replicated these results comparing three groups characterized by
a history of impulsive aggression, aggression secondary to paranoid schizophre-
nia, or premeditated aggression (Stanford et al., 1998). Results from this study
indicated reduced P300 amplitude in both the impulsive and schizophrenia-
related aggression groups relative to the premeditated aggression group.
Prospective Psychophysiological Research
Findings of electrodermal (e.g., SC), cardiovascular (e.g., HR), and cortical (e.g.,
EEG and ERP) underarousal as a predisposition for the development of criminal
behavior have been supported in prospective longitudinal studies (Loeb & Med-
nick, 1977; Mednick et al., 1982; Petersen et al., 1982; Raine, Venables, &
Williams, 1990a). In addition, Raine, Venables, and Williams (1990b,c) found a
reduced number of SC and HR orienting responses and larger N100 ERPs in 15-
year-old criminals to be. The most common form of criminal offenses included
burglary and theft, which suggests that these findings may be particularly rele-
vant to the development of serious, but less violent, forms of crime.
Summary of Psychophysiological Findings
In sum, studies of SC, HR, and EEG, including prospective studies, implicate
underarousal in the development of antisocial behavior. These studies, however,
have consisted of individuals primarily committing nonviolent forms of crime or
having less serious aggression. Autonomic reactivity of SC and HR, on the other
hand, seems to characterize impulsive-emotional forms of aggression (Scarpa &
Raine, 1997), especially when the aggressor is exposed to a provocation and per-
ceives the provocation as intentional (Pitts, 1993; Zillmann, 1983). As such, con-
sistent with the idea of impulsive-emotional aggression, these findings suggest
that psychophysiological reactivity is related to aggression in the context of in-
creased negative affect and thought processes that would increase the likelihood
of negative affect.
Studies of ERP implicate reduced P300 amplitudes in impulsive-emotional ag-
gressors. It has been suggested that such reduced amplitude is the result of prob-
lems with higher order cognitive processing and attention (Barratt et al., 1997)
or more general low arousal (Gerstle, Mathias, & Stanford, 1998). Because un-
derarousal in other systems seems related to nonviolent or mild aggressive be-
havior, deficits in cognitive processing may be the more likely explanation of re-
duced P300 in impulsively violent individuals. This would be consistent with
executive cognitive dysfunction and affect dysregulation associated with fron-
totemporal deficits.
SUMMARY
Previous work has indicated the existence of several types of aggressive behav-
ior in animals that primarily fall into two categories: defensive and predatory ag-
gression. In humans, it has been suggested that two parallel forms of aggression
or violence exist (i.e., impulsive-emotional and controlled-instrumental) with dis-
tinct biopsychosocial pathways (Vitiello & Stoff, 1997). The work of Dodge et
al. (1997) indicates specific cognitive biases, emotional regulatory difficulties,
and stressful life events in children with impulsive-emotional forms of aggres-
sion. Based on previous findings on the biological bases of antisocial behavior,
this chapter was designed as an initial attempt to delineate neurobiological vari-

ables that may contribute to impulsive-emotional forms of violence. Few such
studies specifically distinguish types of violence. Taken together, however, the
research reviewed on neuropsychological, neurochemical, hormonal, and psy-
chophysiological relationships to antisocial behavior suggest that there indeed
may be specific biological underpinnings to impulsive-emotional aggression. The
relationships are currently speculative, but point to the importance of distin-
guishing forms of violence in future research. An overall summary of these find-
ings is presented in Table 13.1.
Neuropsychological testing, brain lesion, brain imaging, EEG, and ERP stud-
ies implicate multisite brain dysfunction, particularly affecting frontotemporal
limbic sites, in relationship to violence. These findings must be qualified by the
fact that many violent offenders have no substantial brain damage, lesions, or
dysfunction, but this does not rule out the possibility of subtle neuropsycholog-
ical effects on decision-making and impulse control. Giancola (1995), for ex-
ample, suggests that frontal cortex impairments in executive cognitive functions
involving planning, abstract reasoning, attention, and behavior regulation in re-
sponse to environmental feedback may increase the risk for aggression by lead-
ing to (7) misattributions of threat and hostility in conflict sutuations, (2) in-
ability to generate socially acceptable solutions in response to anger situations,
(3) inability to execute actions that will avoid an argument or aggressive inter-
action, or (4) poor behavioral control over hostile cognitions and negative affect.
Table 13.1. Summary of Findings Relating Neuropsychology, Neurochemistry,

Hormones, and Psychophysiology to Impulsive-Emotional Aggression in Humans
Neuropsychology
Decreased frontotemporal functioning, possibly disrupting limbic functioning
and activating the amygdala
May be particularly localized to left hemisphere deficits and relative activation of the
right temporal lobe
Neurochemistry
Decreased central serotonin in combination with
Decreased central norepinephrine
No relationship with central dopamine
Hormones
No relationship with testosterone
Increased cortisol levels and reactivity
Decreased blood sugar levels (i.e., hypoglycemia)
Psychophysiology
EEG abnormalities, particularly increased alpha activity in frontal lobes
Reduced P300 amplitude
Increased heart rate reactivity
Possibly larger skin conductance responses
Newman and colleagues (see Wallace, Bachorowski, & Newman, 1991) have
suggested that frontal cortex impairments of executive functioning leads to the
impulsivity found in many individuals with disinhibitory psychopathology (in-
cluding antisocial people) by activating their responsivity in the face of compet-
ing reward and punishment. Thus, if frontal dysfunction (or multisite limbic dys-
function) exists in an aggressive individual, it seems most likely to relate to
impulsive-emotional forms of aggression.
This conclusion is further supported by findings in related physiological sys-
tems, which include a combination of decreased serotonergic activity and nora-
drenergic dysregulation, cortisol reactivity indicative of HPA axis dysregulation,
hypoglycemia, and autonomic HR reactivity. These biological systems seem to
increase the propensity for negative affect and arousal, impair the ability to reg-
ulate that affect/arousal, and lead to biased thought processes, thus increasing
risk for impulsive-emotional aggression (Scarpa & Raine, 1997).
CONCLUSION
Neurobiological effects on aggression are by no means simple or straightforward,

and they reflect the complexity of the manifestation of violent behavior. First, as
evidence of this complexity, the biological findings reviewed here are not an ex-
haustive list. Other biological factors that may contribute to crime and violence,
but are not covered here, include those influenced by other types of brain injury
or dysfunction, genetics, pregnancy and birth complications, physical appearance,
diet, and exposure to toxins such as lead (for review, see Raine, 1993). Second,
none of these factors has been found to individually and accurately predict vio-
lent behavior. Rather, they are to be viewed as risk factors that singly, or in com-
bination, increase the likelihood that someone may react defensively and impul-
sively with aggression. Third, most of these studies were conducted with
exclusively male samples. The generalization of such findings to female violence
is thus extremely limited. Fourth, social and psychological factors have also been
found to predispose to crime and violence, and such contributions need to be in-
tegrated into biological research to form a more comprehensive understanding of
the manifestation of emotional aggression.
This last point is particularly relevant to individuals displaying impulsive-
emotional aggression given their increased likelihood of stressful life events and
physical abuse (Dodge et al., 1997). There are several examples of such complex
interactions in biological research of antisociality. For example, the finding of lower
resting HR in antisocial samples is particularly strong in those from higher social
classes (Raine & Venables, 1984) and in intact families (Wadsworth, 1976). To
explain such findings, it has been suggested that in relatively benign environments
where the "social push" for antisocial behavior is lower, biological determinants
of such behavior assume greater importance (Raine & Venables, 1981). Others
have found that the risk for violent offending, on the other hand, is heightened
when both biological and social risk factors are present. Mednick and Kandel
(1988), for example, found the greatest degree of violence in individuals who
had both minor physical anomalies (thought to reflect a disruption to fetal neural
development in the first trimester of pregnancy) and came from unstable nonin-
tact home environments. In a group of children with disruptive behavior disor-
ders, Scarpa (1997) and Scerbo and Kolko (1995) found the greatest degree of
aggression in those who had a history of physical abuse coupled with physio-
logical or emotional dysregulation. Taken together, these latter studies demon-
strate the sensitivity of individuals to adverse social environments, especially if
they have predispositions that can influence their emotionality and emotion reg-
ulatory abilities.
Finally, the distinction between factors that are biological versus psychologi-
cal or environmental is necessarily artificial. That is, any factor may directly or
indirectly affect another. Some biological correlates of violence, for example,
may be environmentally caused (e.g., brain damage resulting from blows to the
head). Furthermore, the biological correlates reviewed herein are likely to have
psychological effects (e.g., brain damage may impair intellectual and other cog-
nitive functioning). This highlights again the complexity of human antisocial be-
havior and the mistake of conducting such research under the assumption of a
false environmental versus biological dichotomy.
In conclusion, evidence is provided that suggests that impulsive-emotional forms
of aggression (accompanied by anger and impulsivity) may indeed be partly me-
diated through neurobiological mechanisms. Because much of the violence occur-
ring today involves interpersonal situations within familiar social circles, such as
domestic violence and abuse, the examination of such reactive emotional aggres-
sion becomes crucial. As a more complete understanding is gained of the complex
interplay of biological, cognitive, social, and emotional forces involved in such vi-
olence, we are afforded optimism that it can be minimized in the future.
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14
Differentiation of States and Causes of Apathy
DONALD T. STUSS, ROBERT VAN REEKUM,

AND KELLY J. MURPHY
Apathy is best characterized in behavioral terms as an absence of responsiveness

to stimuli as demonstrated by a lack of self-initiated action. The main thesis of
this chapter is that there are different kinds of apathy. Each is separable on the
basis of both the anatomical regions and the psychological mechanisms involved.
The chapter is organized into four main sections written with the aim of estab-
lishing support for this thesis. In the first section, definitions of apathy are re-
viewed, and we introduce our approach to defining apathy states. The second
section describes common causes of apathy and outlines the neuroanatomical re-
gions involved. In the third section, we present our proposed conceptualization
of the different kinds of apathy. The fourth section contains a review of what is
known about treatment interventions for apathy.
THE DEFINITIONS OF APATHY
We use apathy as our general label. The word apathy consists of the prefix a,
meaning without, and pathos, the Greek word for passion. Apathy is therefore
most commonly defined as a lack of interest or emotion. In this sense, synonyms
such as indifference and flat affect are commonly used in the neurological and
neuropsychiatric literature. However, pathos can also indicate suffering. Dictio-
340
Differentiation of States and Causes of Apathy 341
nary synonyms and adjectival phrases provided for apathy include destitute of
feeling, insensible, indifferent, impassive, lethargic, stoic, and unconcerned. Al-
though there is a clear communal theme among these phrases and words, there
is also a range of connotations and thus the potential for a lack of precision in
the clinical definition of apathy.
One reason concepts of apathy lack precision is the fact that apathy is often sec-
ondary to different neurological and psychiatric disorders and as such is often con-
sidered to incorporate some of the features of the related disorder or syndrome into
its definition. For example, Fisher (1983) described the disorder abulia as impaired
spontaneity in action and speech against a background of normal intellectual con-
tent, reduced range of movement, mental slowness, decreased attention in the pres-
ence of increased distractibility, and apathy. Clearly, abulia and apathy overlap or
are coexistent in Fisher's conceptualization. Marin (1990, p. 22), in an admirable
attempt to refine and limit the range of the term apathy, suggested the following
definition: "diminished motivation not attributable to diminished level of con-
sciousness, cognitive impairment, or emotional distress," excluding not only states
such as depression, demoralization, delirium, and dementia but also abulia, akine-
sia, and akinetic mutism. Hence, Marin's view of apathy appears to differ from
that of Fisher. Marin views apathy and abulia as being mutually exclusive, whereas
Fisher (1983) views apathy as being a characteristic of abulia. Distinct definitions
of strongly related states are clearly very difficult to achieve.
Marin (1991,1996) differentiated between apathy as a symptom of other prob-
lems (such as depression or altered level of consciousness) and apathy as a syn-
drome. In the description of apathy as a syndrome by Marin, Biedrzycki, and
Firinciogullari (1991), the key feature remains a lack of motivation (amotiva-
tional state). In his more recent reformulation, Marin (1996) adopted a diagnos-
tic-based approach to propose criteria for the diagnosis of apathy. The inclusion
criterion is the presence of amotivation in any of the realms of affect, behavior,
and cognition, and exclusion criteria include the presence of disordered arousal,
depression, or causative cognitive impairment.
Recently, Berrios and Gili (1995) proposed a more philosophical conceptual-
ization of disorders involving pathology of action, stating that such disorders were
best described as an "absence of will." Although it is not clear whether all mani-
festations of apathy reflect a disturbance of will, there is a sense of the importance
of the concept of an absence of self-initiated behavior hi the definition of apathy.
We argue for a formulation of apathy that differs in several ways from the
concepts of apathy reviewed above. Apathy cannot be clinically defined as sim-
ply a lack of motivation. First, there are difficulties inherent in the assessment
of motivation. To be amotivated is to be lacking in the inner urge that moves or
prompts one to action. The assessment of inner urges is problematic and usually
necessitates inference based on observations of affect or behavior. Second, when
one considers all of the pathological and clinical states that may produce apathy
(see below and Marin, 1990, 1991, 1996; Marin, Biedrzycki, & Firinciogullari,
1991), almost all of these "states" contain features in addition to the narrow
"lack of motivation" definition. Employing syndromal criteria, like that sug-
gested by Marin, is also potentially limiting. Recent accumulation of knowledge
in neuroanatomy and neuropsychology provides support for the specification of
different kinds of apathy. Consider, for example, frontal lobe injury, a major
cause of apathy. There is now empirical data demonstrating the specificity of
attention and memory functions within the frontal lobes (Shallice & Burgess,
1991; Stuss et al., 1994a,b; Stuss, Picton, & Alexander, 1999). Stuss and Ben-
son (1986) have indeed distinguished between two kinds of apathetic behavior:
disorders of drive primarily related to the medial frontal regions and disorders
of arousal primarily related to lower neural axes such as the brain stem reticu-
lar formation, specific brain stem nuclei, and the thalamus. It is thus likely that
behavioral disorders fitting under the umbrella of apathy might also demonstrate
greater anatomical and functional specificity in the frontal lobes of the brain and
related brain structures.
Our definition of apathy, "an absence of responsiveness to stimuli as demon-
strated by a lack of self-initiated action," allows for objective behavioral mea-
surements. We contend that apathy is not a singly definable state, nor is it a sin-
gle syndrome. Apathy can be divided into separable types or states that differ in
both the functional disturbances underlying the clinical presentation and the
neural substrates of involvement. Using an adjectival phrase with the term apa-
thy provides us with the necessary increases in scope and specificity of defini-
tion. Furthermore, the use of adjectival modifiers promotes greater consistency
across studies in terms of identifying the type of apathetic behavior being in-
vestigated and how this behavior is measured.
CAUSES OF APATHY
An overview of the reported causes of apathetic behavior (Table 14.1) is essential

for clinical purposes and for providing the background context against which our
proposed conceptualization of apathy is introduced. To provide a background for
our neurological dissociations, the examples presented below selectively review
three major central nervous system (CNS) causes of apathy: localized brain dys-
function, dementias, and psychiatric disorders. Other causes of apathy, which are
not easily related to CNS disturbances, are noted in Table 14.1 but not discussed.
Localized Brain Dysfunction
The most commonly described focal neurologic cause of apathetic behavior is

damage to the frontal lobes. Early clinical case studies frequently reported a
Table 14.1. Common Causes of Apathy States*

Localized brain dysfunction
Dorsolateral prefrontal cortical damage
Medial frontal (cingulate gyrus/supplementary motor area) damage
Frontal systems damage involving subcortical connections to basal ganglia and
thalamus
Dopaminergic hypoactivity affecting mesolimbic areas
Brain stem lesions affecting catecholamine function (ventral tegmental nucleus of the
thalamus)
Limbic drive dysfunction (bilateral lesions of the amygdala and anterior temporal
poles, as in human Kliiver-Bucy syndrome)
Dementia
Frontal/subcortical dementias
Later stages of all progressive dementias
Psychiatric disorders
Major depressive episodes
Schizophrenia (the negative symptoms)
Grief and adjustment disorders
Other causes
Lack of environmental incentive or reward (institutionalization, role loss,
dissatisfaction)
Loss of primary sensory function (deafness, blindness)
Metabolic disturbances
Sleep disorders
Chronic pain
*Based on both Marin (1996) and our clinical experience.
diminution in initiated behavior (for reviews, see Stuss & Benson, 1986; Stuss
et al., 1992). This apathy was observed behaviorally but was also demonstrated
on neuropsychological tests such as verbal fluency (Belyi, 1979; Masdeu &
Shewmon, 1980). In fact, a key observation that led to the use of frontal lobot-
omies for psychiatric disturbances was that frontal lobe lesions in monkeys made
the animals more placid (Jacobsen, 1936; Moniz, 1937). Both left dorsolateral
and superior medial frontal regions demonstrate the most decreased verbal flu-
ency (Stuss et al., 1998).
Another commonly reported acquired neurological cause of apathetic behavior
is damage to the basal ganglia, particularly if the damage is bilateral. A review
of 240 patients with lesions in the caudate nucleus, putamen, or globus pallidus
revealed that apathy was the most common behavioral disorder after basal gan-
glia stroke, occurring in approximately 13% of cases (Bhatia & Marsden, 1994).
The apathetic behavior was most common after caudate lesions (26%), and was
never found in the 20 patients with putamen lesions. The behavioral consequence
of basal ganglia damage was called psychic akinesia, a disturbance of psychic au-
toactivation (Ali-Cherif et al., 1984; Habib & Poncet, 1988; Laplane et al., 1984;
Percheron et al., 1994) linked to an impaired dopaminergic mesolimbic system
(Poncet & Habib, 1994). There is a dramatic decrease in spontaneous behavior of
any kind, including thought, and verbal fluency (Alexander, Naeser, & Palumbo,
1987). The observed behavioral aspontaneity contrasts with the relatively normal
reaction to external stimuli and commands. In other words, such individuals re-
spond appropriately to external stimulation from the people and general environ-
ment around them, but they do not demonstrate self-initiated behavior.
Another common focal neurologic cause of apathy is damage to the dorso-
medial thalamic nucleus. This is also most striking and persistent with bilateral
lesions (Bogousslavsky et al., 1988; Guberman & Stuss, 1983; McGilchrist et
al., 1993). Patients with dorsomedial thalamic damage often exhibit apathetic be-
haviors consistent with those described above.
The extreme form of apathetic behavior is akinetic mutism wherein the patient
exhibits normal sleep-wake cycles but rarely, if at all, initiates behavior in any
modality (Plum & Posner, 1980). The proposed causes are variable. Some re-
searchers have suggested that akinetic mutism is related to disruption in the as-
cending input from the reticular activating system, perhaps due to medial fore-
brain bundle lesions (e.g., Cairns et al., 1941; Ross & Stewart, 1981). Still others
have proposed that the etiology for akinetic mutism is a loss of limbic drive and
activation secondary to bilateral anterior cingulate lesions, which is believed to
play a role in limbic motivation (e.g., Devinsky, Morrell, & Vogt, 1995; Laplane
et al., 1984; Mega & Cummings, 1994). Akinetic mutism has also been reported
secondary to bilateral globus pallidus/internal capsule lesions. This is particu-
larly true for lesions with ventral extension because these may disconnect the an-
terior cingulate from involvement in limbic motivational activity (Mega & Co-
henour, 1997).
In most of the focal neurologic etiologies of apathy noted above and in Table
14.1, there is a direct or indirect anatomical involvement of the frontal lobes
and/or limbic drive. Each of the nonfrontal areas mentioned above has extensive
reciprocal connections with the frontal lobes and are component parts of frontal
systems (Fuster, 1989; Pandya & Barnes, 1987; Stuss & Benson, 1986). More-
over, similar apathetic behaviors have been shown after pathology in deep frontal
white matter (Poncet & Habib, 1994). Descriptions of apathetic behavior after
capsular genu infarct note behavioral sequelae that are consistent with the inter-
ruption of the inferior and anterior thalamic peduncles, resulting in functional de-
activation of the ipsilateral frontal cortex (Tatemichi et al., 1992; Yasuda et al.,
1990). Bilateral lesions of the amygdala and anterior temporal poles, as in hu-
man Kliiver-Bucy syndrome, often results in apathy that is likely due to limbic
drive damage (Marin, 1996). Evidence from neuroimaging research also demon-
strates a link between the frontal lobes and apathy even in the absence of focal
frontal brain damage. For example, McGilchrist et al. (1993), using single pho-
ton emission computed tomography (SPECT) to measure regional cerebral blood

flow, found hypometabolism in the frontal brain regions of a patient presenting
with apathetic behavior following bilateral dorsomedial thalamic lesions. It ap-
pears that frontal lobe involvement, involvement of structures supportive of
frontal system function, and/or dysfunction in limbic motivational regions are a
necessary requirement for apathy secondary to most focal neurologic disorders.
Dementia
Patients with frontotemporal lobar dysfunction (frontal lobe dementia) often ex-
hibit apathy as an important symptom (Snowden, Neany, & Mann, 1996). Sim-
ilar to patients with acquired basal ganglia lesions, individuals who have pro-
gressive disorders involving the basal ganglia, such as Parkinson's disease and
Huntington's disease, have impaired initiation of behavior (Mayberg, 1994). Such
patients often reveal varying degrees of apathy, bradyphrenia (slowness in think-
ing), and psychomotor slowing. Huntington's and Parkinson's disease patients
may also be depressed, however, and the influence of depression on behavior
must be dissociated from the influence of apathy. A large percentage of patients
with Alzheimer's disease have also been reported to have apathy and diminished
initiative (Bozzola, Gorelick, & Freels, 1992; Reichman et al., 1996). Such lack
of interest of some Alzheimer's disease patients in self-care and other personal
activities may exist in some patients independent of depression or other symp-
toms (Reichman et al., 1996). In a SPECT study of 40 Alzheimer patients, the
degree of apathy was correlated with decreased right temporoparietal perfusion
(Ott, Noto, & Fogel, 1996). For aging individuals, there is some suggestion that
the degree of apathy is related to the severity of the cognitive disorder (Forsell
et al., 1993). These findings suggest that apathy secondary to Alzheimer's dis-
ease may be qualitatively different from apathy due to some focal lesions in which
intellectual functioning as measured by IQ tests may be intact (even though spe-
cific cognitive disorders may be revealed).
Psychiatric Disorders
Apathy related to psychiatric diagnoses has primarily been recognized in patients

with depression and schizophrenia. In depression, the emphasis has been on dif-
ferentiation of apathy and depression in various neurological populations (Stark-
stein et al., 1992). Starkstein and colleagues (1992) studied depression and apa-
thy in idiopathic Parkinson's disease patients. Approximately 12% showed apathy
as their primary psychiatric problem, while 30% were both apathetic and de-
pressed. Apathy was related more to slowness of speed on Trail Making Test
Part B than to accuracy of performance, and depression was associated with in-
creased errors but not significant slowness of response time, suggesting that ap-
athy and depression were dissociable. Such a dissociation between apathy and
depression has also been reported in other patient groups. Marin et al. (1993)
found that apathy in the absence of depression was seen most frequently in pa-
tients with Alzheimer's disease and right hemisphere stroke, and less frequently
in patients with left hemisphere stroke or in normal subjects. In the subjects with
major depression, apathy scores were positively associated with depression
scores, although apathy was occasionally absent in some of these subjects. Forsell
et al. (1993) studied elderly depressed subjects with and without dementia and
found that the mood symptoms of this population clustered into two groups: mood
disturbance and motivational disturbance. Mood symptoms were most frequent
in those subjects with mild dementia, and motivational disturbances were most
frequent in those with more advanced disease. Thus, although apathy may be
seen in depression, it is also dissociable from depression.
Research on schizophrenia has had a significant impact on the understanding
of apathy since the distinction between positive and negative symptoms was first
made (Andreasen, 1982; Crow, 1985). The negative symptoms clearly include
the concept of apathy. Frith (1987) argued that negative symptoms reflect a sub-
jective internal failure of willed intention, in other words, a deficit in initiation.
Crow (1995) argued that the negative symptoms could reflect a failure in brain
development. This hypothesis would be compatible with the correlation between
negative symptoms with cognitive impairment and the presence of personality
change in these patients before the actual onset of the diagnosed illness. Strauss
(1993), following Frith and Done (1989), suggested that positive and negative
symptoms could be related to two separate anatomical systems: positive symp-
toms to dysfunction in the interaction of frontal/septohippocampal systems and
negative symptoms to abnormalities in frontostriatal interconnections.
In summary, our selective review of causes of apathetic behavior leads to two
conclusions. First, the term apathy has been used quite differently by different
authors, and there appears to be a range of behavioral and affective changes that
are inadequately described under single definitional or syndromal descriptions of
apathy. For example, disorders of "willed" intention are very different from the
difficulty in initiation found in patients with degrees of akinetic mutism. It is dif-
ficult to ascribe this entire range of apathetic behaviors simply to a lack of mo-
tivation. Second, there appears to be increasing evidence of frontal/subcortical
or frontolimbic circuitry involved in most types of neurologically based apathy.
A CONCEPTUALIZATION OF APATHY STATES
In this section we outline different types of apathy. The kinds of apathy are dif-
ferentiated by inclusion of an adjective modifier that denotes the major qualities
of the kind of apathetic behavior referred to. The different forms of apathy are
related to damage to different regions in frontal anatomical functional systems.

To some degree, our proposed conceptualization of apathy states derives from
the model of frontal lobe function developed over the years by Stuss and col-
leagues (e.g., Alexander, Benson, & Stuss, 1989; Stuss, 1991b; Stuss et al., 1995,
1998; Stuss & Benson, 1986, 1987).
Apathy Related to Disturbed Arousal
Frequently apathy is described as a symptom associated with many disorders of

arousal. In considering apathy related to disturbed arousal, the distinct aspects of
disturbed arousal should be differentiated. Fernandez-Duque and Posner (1997)
suggest, for example, that alerting and orienting are dissociable, with separate
mechanisms and different biochemical bases. This is similar to the concept of
phasic and tonic attention (Benson & Geshwind, 1975) or the different types of
delirium (Lipowsky, 1990). Others (Plum & Posner, 1980) describe a continuum
of arousal, from coma through stupor to obtundation. In all of these disorders of
arousal related to brain stem reticular activity system dysfunction, there is a lack
of self-initiated activity. The apathy is usually not the most obvious problem in
these patients, however, and as such the clinical value of the apathy label is likely
to be limited. In our conceptualization, we exclude all disorders of arousal in
which there is an impaired sleep-wake cycle. Similarly, if the cortex is so pro-
foundly damaged that there is no content of consciousness despite normal
arousal—the persistent vegetative state—it would be inappropriate to label a pa-
tient as simply apathetic.
One particular disorder, akinetic mutism, deserves to be labeled apathy asso-
ciated with disturbed arousal. Damage limited to the dopaminergic ventral
tegmental brain stem nucleus or its projections to frontal cortex via the medial
forebrain bundle will result in diminished general responsiveness against a back-
ground of normal sleep-wake cycles and intact cortical functions. Although the
patient is cognitively capable, self-initiated and purposeful cortical functioning
does not normally occur. Occasionally, however, under conditions of emotion-
ally potent stimuli or when requests are not cognitively demanding, responsive-
ness may be observed. Considering this type of apathy as arousal apathy may be
appropriate as the medial forebrain bundle conveys ascending reticular activat-
ing system information to modulate the effects of arousal in the cortex.
Apathy Associated with Frontal System Dysfunction
This apathy is related not just to the frontal lobes themselves but also to
frontal/subcortical connectivity (for an overview of frontal/subcortical connec-
tions, see Alexander, DeLong, & Strick, 1986; Cummings, 1993; Mega & Cum-
mings, 1994). Five frontal/subcortical circuits have been described. Each circuit
includes the same general brain regions: frontal lobe, striatum, globus pallidus,
substantia nigra, and thalamus. The five circuits are divisible into two major func-
tional categories, motor and behavioral. Although damage to any of the five could
be considered within the general term executive apathy, we propose that damage
to any one of the five circuits results in distinctly different forms of executive
apathy.
The two motor circuits are the oculomotor and the general motor circuits. The
relation of each to the frontal lobes is to the frontal eye fields and the supple-
mentary motor area (SMA), respectively. For the two motor circuits, two differ-
ent types of apathetic behavior have been described. For the oculomotor circuit,
there is a tendency not to initiate responses to the contralateral side. This occurs
for both vision (Hecaen & Albert, 1978) and motor (Spiers et al., 1990) responses.
This is frequently evidenced in neglect. Damage to the SMA circuit results in
two types of reported apathetic behavior. There is a decrease in verbal output as
evidenced by a decrease in verbal fluency (Alexander, Benson, & Stuss, 1989;
Stuss & Benson, 1986). While diminished verbal fluency is frequently observed
after left dorsolateral frontal lesions, it is also common after damage to either the
right or left SMA (Stuss et al., 1998). The second type of apathetic behavior as-
sociated with SMA pathology is the alien hand disorder. Although most com-
monly described as a type of impulsive behavior (i.e., a positive but unwilled ac-
tivity of the contralateral [usually left] hand), there have also been descriptions
of occasional apathy, an inability to move the left hand at will (Baynes et al.,
1997; Feinberg et al., 1992; Tanaka et al., 1996).
The three behavioral circuits are related to the dorsolateral prefrontal, lateral
orbital, and anterior cingulate regions, respectively. The dorsolateral prefrontal
circuit has been proposed as originating in the convexity of the lateral surface of
the anterior frontal lobe. The lateral orbital circuit initiates in Brodmann area 10.
The anterior cingulate is the site of origin for the final behavioral circuit. Dif-
ferent types of apathetic behavior have been associated with damage to these
three behavioral circuits (Bhatia & Marsden, 1994). Apathy, because it is a dis-
order of self-initiated behavior, is particularly susceptible to damage to these
frontal/subcortical circuits because each is an effector circuit enabling action in
the environment (Cummings, 1993).
The dorsolateral prefrontal circuit is characterized by a decrease in verbal flu-
ency as well as by disturbance in active selection of behaviors. This lack of be-
havioral response after dorsolateral frontal damage can be considered as apathetic
behavior. Arousal is normal, and general cognitive functions are intact. The spe-
cific type of executive apathy can be explained by a simple model of respon-
siveness (Stuss, 1991a,b; Stuss, Picton, & Alexander, 1999). In any behavior,
there is an input and a response-output pathway. Incoming information is com-
pared with stored information—a constructed model or template. This normally
leads to a response of some type, including the potential generation of a new,
adapted model. At the level of executive functions, the responses are those that
require flexibility, selection, novel responsiveness, and so on, controlling the
more automatic functions of posterior areas. If there is damage to the template
(the specific type of executive process) or to the comparator, then the outcome
is impaired behavior or the absence of behavior. Thus, in the above examples,
the absence of behavior could be considered as executive apathy (i.e., the
absence of initiated behavior secondary to a disorder of executive cognitive
functioning.
Damage to the lateral orbitofrontal cortex results in personality blunting and
change. Again, this can be viewed as a type of apathetic behavior due perhaps
to the absence of limbic affective input. As noted earlier, orbitofrontal loboto-
mies were often performed to make patients easier to get along with. A current
example related to the ventral medial frontal region but perhaps appropriate here
involves the demonstrated inability to anticipate selection of response in a gam-
bling task. Despite normal arousal, the absence of responses would reflect a dis-
order of self-initiated behavior, or apathy (Bechara et al., 1996).
The most obvious frontal type of apathy results from damage to the anterior
cingulate. Damage to this region, particularly if bilateral, results in apathy and
lack of initiation. The classification of anterior cingulate executive apathy is it-
self too broad, and even more specific subtyping may be required. Devinsky,
Morrell, and Vogt (1995) point to the considerable anatomical and connective
specificity of the anterior cingulate. The association to the rostral limbic system
suggests that a major role of the cingulate is to assess the motivational informa-
tion from internal and external stimuli. Because of the connectivity, however,
subtypes of apathetic behavior might result from cingulate pathology. For ex-
ample, chronic pain patients treated with cingulomotomy continue to feel pain,
but they are no longer bothered by it (Foltz & White, 1968). Damage to the an-
terior cingulate results in affective placidity, lack of emotional response, and al-
tered social interactions—all of which are reflective of apathy. Anterior cingu-
late damage can also result in impaired response selection and decision to respond
(symptoms representative of apathetic behavior), as well as impaired movement
execution itself. Devinsky and colleagues suggest very specific anatomical lo-
calization for the different subtypes of apathy: affective placidity (connection of
Brodmann areas 24/25 with the amygdala), impaired response selection (gyral
surface of anterior cingulate, areas 24a' and 24b'), and impaired movement ex-
ecution (interconnection of 24c' with the SMA). In other words, the types of ap-
athy revealed are related to the cingulate itself and to the connections of the cin-
gulate with other regions.
The five frontal sites of origin result in different types of apathy, and this dis-
tinction is paralleled in the subcortical regions of each circuit. That is, damage
to different parts of the same circuit can result in similar impairments. Thus, dam-
age to the frontal lobes of the dorsolateral prefrontal circuit will lead to similar
results as damage to the connected subcortical areas such as the caudate, globus
pallidus, and thalamus. Because of the compressed nature of these subcortical
regions, however, differentiation of forms of apathy specific to one circuit is al-
most impossible to determine. Nevertheless, some dissociation at this level has
been suggested. Studies of the basal ganglia indicate that different types of apa-
thy may occur (Schultz et al., 1993; Williams et al., 1993). Similar suggestions
of dissociation have been reported after thalamic lesions. McAlonan, Robbins,
and Everitt (1993) suggested that the dorsal medial nucleus, through its inter-
connections with the ventral striatal pallidal and prefrontal cortex, might be in-
volved in response selection. A flat affect (unconcern), and physical withdrawal
and akinesia, may differentiate dorsomedial and anterior thalamic lesions (Graff-
Radford et al., 1984; Stuss et al., 1988).
The above types of apathy associated with frontal system dysfunction are re-
lated more to the direct effector responsiveness in which the frontal lobes play
an important role. A more abstract form of apathy also likely exists, related to
the frontal lobes and primarily their linibic connections. Evidence is accumulat-
ing for the role of the anterior frontal lobes (the right frontal, ventral medial, and
possibly polar regions have been particularly implicated) in awareness of self and
social awareness (Damasio et al., 1994; Stuss, 1991a,b; Stuss, Picton, & Alexan-
der, 1999; Wheeler, Stuss, & Tulving, 1997). Self and social awareness is a
metacognitive ability that is necessary to mediate information from a personal,
social past and current history with projections to the future. The key feature of
this apathy appears to be intact knowledge of behavior, even of intention, but a
lack of action in one's own self-interest—a type of "social apathy" (Stuss, Pic-
ton, & Alexander, 1999). The patient appears not to have a mental model of his
or her own self that serves to organize perceptions and actions. This type of so-
cial apathy is evident in the clinical descriptions of patients such as Phineas Gage,
those with the Capgras syndrome, and even in disorders of humour (Alexander,
Stuss, & Benson, 1979; Damasio et al., 1994; Shammi & Stuss, 1999; Stuss &
Benson, 1986).
Comparisons Between our Conceptualization of

Apathy States and Other Views
Our approach to understanding apathy shares some commonalties with other con-
ceptualizations of apathy. The idea of apathy being associated with frontal/
subcortical circuits has been discussed by others (e.g., Bhatia & Marsden, 1994;
Cummings, 1993; Mega & Cummings, 1994). The separation of positive and
negative symptoms in schizophrenia has led to the proposal of distinct frontal
system dysfunctions underlying the two symptom groupings (Frith, 1987; Frith
& Done, 1989; Strauss, 1993). Mega and Cohenour (1997), in their review of
akinetic mutism, proposed that there may be three different kinds of disturbed
activation of behavior: motor, cognitive, and limbic. Our idea of comparison and
generation processes in the construction of models of the world is somewhat sim-
ilar to that of Godefroy and Rousseaux's "relative judgment theory" (1997). Turk-
stra and Bayles (1992), in their model of mutism, suggested that speech pro-
duction depended on five interrelated processes: arousal; cognitive processes;
affect and drive; motor initiation; planning; programming and coordination; and
execution of movement. If verbal output is considered as a measure of apathy,
as has been done, then it is clear that disturbances in very different mechanisms
and brain areas could lead to the same decreases in output. Our research on ver-
bal fluency has shown that impairments in different processes can affect self-
initiated behavior such as word generation (Stuss et al., 1998; Troyer et al., 1998).
In summary, our conceptualization of apathy states is based on the known clin-
ical presentations and separable neuroanatomical substrates of apathetic behav-
iors. This conceptualization will of necessity be modified as we continue to learn
more about the various types of apathy and their neural correlates. For example,
as our knowledge of the specificity of functioning within the frontal lobes in-
creases, and our mapping of the interconnections of frontal, cognitive, and lim-
bic regions is completed, our understanding of the exact nature of the circuits
may alter. We are arguing more for an approach than for absolute distinction
among these frontal system types of apathy. We do not have experimental data,
and in reality it may be difficult to dissociate unique causes. The major point is
this: If the causes of observable apathy are distinguishable to some degree, then
treatment and rehabilitation can be more specific. At present, we believe that the
presented view of apathy states is a useful framework within which to view ap-
athy disorders, as well as a guide for targeting specific treatment interventions.
TREATMENT INTERVENTIONS
In this section, we summarize the evidence gathered to date on the treatment of

apathy. Past research and clinical efforts have typically used the concept of ap-
athy as a syndrome. We attempt to relate, as much as possible, the available treat-
ment information to our proposed conceptualization of apathy states.
Pharmacotherapy
Two broad introductory comments need to be made. First, little research into the
efficacy of medication therapy for apathy states has been completed to date. This
in part probably reflects the view of many that apathy is not a significant prob-
lem, if it is a "problem" at all. The clinical relevance of apathy is likely to vary
depending on the clinical setting and/or the philosophical viewpoint of the as-
sessor of its relevance. For example, in a busy nursing home, with severe prob-
lems for staff posed by the disinhibited and aggressive behavior of some resi-
dents, apathetic residents are likely to be largely viewed as somewhat ideal be-
haviorally. On the other hand, apathy in a rehabilitation setting may become a
very significant deterrent to progress. The risks associated with treating apathy
in chronic care settings need to be offset by compelling reasons to treat the ap-
athy (e.g., residents who are so apathetic that they no longer eat).
The second comment relates to the potential temptation to infer neurotrans-
mitter bases for apathy states based on response to treatment. This approach,
while ultimately somewhat validated by other types of data for the dopamine hy-
pothesis of schizophrenia (which of course has its origins in the observed re-
sponse to dopamine-blocking drugs), has been less successful in other domains.
Clearly additional evidence related to neurotransmitter dysfunction over and
above observations of treatment response are required before the neurotransmit-
ter bases of apathy states can be fully understood.
In some case studies akinetic mutism has been treated with bromocriptine
(Crismon et al., 1988; Echiverri et al., 1988; Ross & Stewart, 1981) or
methylphenidate (Daly & Love, 1958; Weinberg, Auerbach, & Moore, 1987).
Although we have excluded apathetic behavior that is coexistent with fluctuat-
ing arousal from our precise definition of apathy, it is of relevance that this type
of apathy is common in states such as post-traumatic amnesia, and some success
has been reported with pharmacological treatment (Jackson, Corrigan, & Arnett,
1985; Mysiw, Jackson, & Corrigan, 1988).
Medications used for this "executive" kind of apathy fall broadly into the three
categories of dopaminergic drugs, amphetamines, and atypical neuroleptics.
Gualtieri et al. (1989) have suggested that apathy in traumatic brain injured (TBI)
patients may have its origins in the axonal shearing of brain stem structures, with
secondary lowering of monoamine transmission, including dopamine, to striatum
and cortex. If the suggestion of Gualtieri et al. (1989) is correct, then medica-
tions dependent on an intact presynaptic neuron may be less effective in TBI-
related apathy. This very hypothesis led Gualtieri et al. (1989) to study the effi-
cacy of amantadine, a drug that increases dopaminergic activity. Benefit in the
treatment of apathy in TBI patients was reported with amantadine; however, the
results were limited by methodological problems. Van Reekum et al. (1995) per-
formed an N of 1 randomized double-blind, placebo-controlled study that showed
effectiveness of amantadine in improving initiation/participation in a subject with
a profound apathy beginning after a TBI. Rehabilitation was facilitated by aman-
tadine in this subject.
Although not directly assessing apathy, other studies have used amantadine
for indications that may have formed part of an apathy state. Improvement in ap-
petite, talkativeness, and activity level were noted in long-term geriatric care pa-
tients treated with amantadine (Roca et al., 1990). Andersson et al. (1992) re-
ported cognitive improvement (i.e., increases in visual attention, speed of
information processing, attention span, learning capacity, and alertness) in two

severe TBI cases treated with amantadine. Reversal of "mute, immobile states"
were noted with amantadine when used for the end-stage of Alzheimer's disease
(Erkulwater & Pillai, 1989). Amantadine may also play a role in reducing fa-
tigue and frontal system cognitive impairments associated with multiple sclero-
sis (Cohen & Fisher, 1989). Although the mechanism of action of amantadine is
likely to be related to increased dopaminergic activity, additional changes in the
brain (e.g., improved frontal system cognitive functioning) in response to aman-
tadine are being identified. For example, Semlitsch, Anderson, and Saletu (1992)
found that the P300 amplitude of targets in an auditory odd-ball paradigm was
significantly augmented (by 30% over baseline) in subjects with mild dementia
who received amantadine.
Bromocriptine is a dopamine agonist that has also been studied in apathy states.
Powell et al. (1996) performed an open study of 11 apathetic subjects (after TBI
or subarachnoid hemorrhage) and showed improvements in motivation and frontal
cognitive functioning, but an absence of change in mood, with bromocriptine.
Parks et al. (1992) showed improved range of affect, less social withdrawal, and
increased assertiveness with bromocriptine in a single male subject after sub-
archnoid haemorrhage (related to an anterior communicating artery aneurysm on
the right side), who also had evidence of a lacunar infarct in the head of the left
caudate. Some "marginal" improvement in right superior frontoparietal lobe per-
fusion was seen in serial HMPAO SPECT scanning with bromocriptine, and there
was also improvement in frontal system, but not visuospatial, cognitive func-
tioning. Muller and von Cramon (1994) also noted improvement in motivational
behavior with bromocriptine in 4 of 15 subjects treated with bromocriptine; in
this series of subjects cognition was not improved with bromocriptine.
Methylphenidate is a frequently used amphetamine, particularly for children
with attention deficit hyperactivity disorder. Several case reports of improvement
in motivational behavior with methylphenidate exist (Marin et al., 1995). An open
study of 88 elderly subjects in a rehabilitation center (for cerebrovascular acci-
dents and so forth) using amphetamine showed that half of the subjects improved
significantly, one-fourth did not change, and one-fourth dropped out because of
the side effects (Clark & Mankikar, 1979). Branconnier and Cole (1980) per-
formed a randomized clinical trial of methylphenidate in elderly apathetic sub-
jects and found improved "vigour." Kaplitz (1975) also completed a randomized
clinical trial with methylphenidate. They studied subjects with "senile apathy";
nurses and physicians noted improvements in interest, involvement, activity level,
and self-esteem.
Much of the methylphenidate evidence reviewed above is limited by diagnos-
tic and assessment issues. More recently, Maletta and Winegarden (1993) re-
ported on three severely demented residents of long-term institutions who showed
gradual onset of apathy "eventually resulting in severe anorexia . . . with con-
sideration of permanent feeding tube placement." Methylphenidate led to signif-

icant and almost immediate improvement in appetite with weight increase.
Galynker et al. (1997) studied 27 subjects with dementia (Alzheimer's disease
and vascular) and found that negative symptoms and cognition both improved
with methylphenidate, while mood symptoms did not. Watanabe et al. (1995) re-
ported on a 38-year-old apathetic male. Neuropsychological testing showed
frontal system deficits, and magnetic resonance imaging showed infarcts in the
subcortical white matter, basal ganglia, cerebellum, and left thalamus. Methyl-
phenidate led to increased interest, social behavior, and hygiene. The pre-methyl-
phenidate SPECT scan showed bilateral frontal hypoperfusion, and the post-
methylphenidate SPECT scan showed significantly increased perfusion frontally.
Finally, Volkow et al. (1997) found that methylphenidate's effects on brain
function were to some extent dependent on the levels of dopamine D2 receptors
throughout the brain and between individuals. Methylphenidate consistently de-
creased relative (to whole brain) metabolism in the basal ganglia and increased
it in the cerebellum. Frontotemporal metabolism was increased in subjects with
high D2 receptors and was decreased in subjects with low D2 receptors.
Although the traditional neuroleptics have done little to improve negative
symptoms in schizophrenia, and might even have worsened negative symptoms,
the newer "atypical" neuroleptics generally have been shown to have treatment
efficacy for negative symptoms (Arvanitis & Miller, 1997; Tran et al., 1997).
These atypical neuroleptics have effects on multiple neurotransmitter subsystems,
and it is as yet unknown which effect is most important in terms of the impact
on negative symptoms. A leading candidate, however, appears to be the antago-
nistic binding to 5-HT2 receptors.
There is little research investigating the concepts of self and social awareness
in pharmacologic studies. Close review of some of the studies discussed above,
however, suggests that subjects did improve in terms of social skills and aware-
ness and acted to preserve their "self" to a greater degree in response to phar-
macologic interventions.
In summary, there is preliminary support for the use of amantadine and other
dopaminergic agents, as well as methylphenidate, for the pharmacologic treat-
ment of some types of apathy. Much of this literature seems to point to the need
to increase dopaminergic activity in the brain as a necessary requirement of suc-
cessful treatment of apathy with medications, although dopaminergic receptor
subtype specificity and interactions with other neurotransmitter systems may also
be important. Because a dopaminergic strategy has been used successfully in so
many different patient groups, it should be evaluated in patients with focal le-
sions resulting in apathy. This approach may be a necessary initial step upon
which specific behavioral treatments are applied. The type of lesion may deter-
mine treatment response, with, for example, presynaptic neuronal damage die-
tating the need for medications that exert direct postsynaptic effects. Finally, this
literature has been somewhat illustrative in terms of identifying changes within
the brain, particularly involving frontal/subcortical functioning, in response to
successful pharmacologic treatment of apathy, and as such this is broadly sup-
portive of the systems we suggest are involved in some apathy states.
Rehabilitation Interventions—Behavioral Therapy
Although rare, there have been reports of successful behavioral therapy treatment
of apathetic states. For example, Rosenthal and Meyer (1971) used a behavior
modification technique with a young woman diagnosed with clinical abulia. These
researchers used a combination of therapy techniques to increase the opportunity
for reward (environmental reinforcers); to reframe the cause of problem behav-
iors using cognitive restructuring; and to set goals, identify goal obstacles, and
establish problem-solving techniques for overcoming these obstacles. The ther-
apy intervention they employed had considerable success. It is important to note,
however, that their client's abulia was not due to central nervous system (CNS)
damage but rather had its origin in non-CNS causes related to lack of environ-
mental incentive or reward and grief and adjustment disorders (see Table 14.1).
Kopelowicz et al. (1997) performed a pilot study with six subjects with schiz-
ophrenia, three of whom had "deficit" syndrome (i.e., cognitive impairment and
increased neurological signs) and three of whom did not (i.e., negative symp-
toms without cognitive impairment). All received 12 weeks of social skills train-
ing. Improvements in social skills and negative symptoms in the nondeficit group
were more impressive than in the deficit group, suggesting that comorbid cog-
nitive impairments may limit rehabilitation efficacy.
Other potentially useful approaches to rehabilitation of apathetic individuals
are based on behavioral rehabilitation of frontal lobe deficits (Prigatano, 1999;
Sohlberg, Mateer, & Stuss, 1993; Stuss et al., 1994c). The authors suggested us-
ing one or more aspects of the following protocol of behavior therapy with frontal
lobe patients: teaching clients compensatory strategies; providing practice on ex-
ecutive tasks (e.g., self-initiation and monitoring); and facilitating self-awareness
and generalization to other behavioral situations. For example, a frontal lobe pa-
tient exhibiting problems initiating and maintaining social interactions might be
taught initiation strategies specific to social situations and provided with an op-
portunity for supervised practice of these learned strategies along with therapy
interventions (e.g., didactic training) designed to increase self and social aware-
ness. All three of these steps would be reciprocally connected, thereby reinforc-
ing each other. The relationship between frontal systems pathology and apathy
indicates that investigation of rehabilitation strategies for frontal lobe injury may
also have utility with patients presenting with apathy.
In summary, behavioral rehabilitation of apathetic behaviors is an area re-

quiring considerable future study. The kind of apathy state and the nature of its
cause (e.g., CNS or non-CNS) are factors that must be considered in the devel-
opment and evaluation of behavioral therapy interventions for individuals pre-
senting with apathetic disorders. We cannot rehabilitate what we do not know
(Stuss, 1987).
CONCLUSION
Our review of apathetic behavior and our apathy model lead us to conclude that
there is no single definition or syndrome of apathy. Although having a single de-
finition or syndrome may be appealing, it inherently limits experimental and clin-
ical approaches, as was the idea of the frontal syndrome. Not all symptoms of
apathy co-occur. Indeed, there is now considerable evidence in the literature for
clinical presentations of separable forms of apathetic behavior.
There are different kinds of apathy, related to different pathophysiological
bases and psychological mechanisms. Although the term apathy is still useful
as a very general description of behavior, it is more parsimonious to describe
the types of apathetic behavior in the context of their pathophysiological and/or
psychological mechanisms. For example, when discussing apathy associated
with disturbed arousal, it is likely worthwhile to distinguish between condi-
tions of altered arousal from the apathy of akinetic mutism that may occur in
the presence of normal sleep-wake cycles. Moreover, there are different types
of executive apathetic disorders, resulting from disturbances in cognitive/af-
fective processes due to damage to specific frontal/subcortical circuits. The
major value in differentiating these executive apathys is to differentiate the
specific cause of the behavior. In many regards it may be best to refer to the
different kinds of executive apathy behaviors according to their cognitive dys-
function rather than as apathy. Finally, social apathy may be the most devas-
tating and the most important type to recognize. The absence of an abstract
model of one's self in society may require the motivation of external en-
vironmental support. One avenue for research is the pursuit of pharmacolog-
ical interventions in conjunction with social awareness and social behavior
training.
Treatment of apathetic behaviors by pharmacotherapy, behavioral therapy, or
both will be most efficacious when the underlying pathophysiological basis and/or
disturbance in psychological mechanisms is clearly understood. In this chapter,
we have attempted to further approaches to treatment by pointing out potentially
different causes of apathetic states and their associated underlying etiologies. The
recognition of the types of apathy is a call for the initiation of rehabilitative
efforts.
ACKNOWLEDGMENTS
Our ongoing research funding, which provided assistance in preparation of this chapter, is gratefully
acknowledged: Medical Research Council of Canada and the Ontario Mental Health Foundation
(D.T.S.); Alzheimer Society of Canada and the Kunin-Lunenfeld Applied Research Unit (R.V.R.);
and Rotman Research Institute postdoctoral fellowship (K.J.M.).
DEDICATION
This chapter is dedicated to the memory of D. Frank Benson, M.D., who was originally to be our
co-author.
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V
CLINICAL IMPLICATIONS
15
Neurological Disorders and
Emotional Dysfunction
KENNETH M. HEILMAN, LEE X. BLONDER,

DAWN BOWERS, AND GREGORY P. CRUCIAN
The domain of emotion, as it has been conceptualized in behavioral neurology

and neuropsychology, includes two major divisions: emotional experience and
emotional behaviors. Whereas emotional experiences can be transient (happy,
sad, angry, frightened, or surprised), emotional moods have a longer duration.
Moods include depression, elation, agitation, and anxiety. Affective disorders can
be considered emotional states that are chronic and pathological. Emotions can
also be described in terms of their valence (positive or negative) and their level
of arousal (low to high). Some have also drawn a distinction between primary
emotions (e.g., happy, sad, angry, frightened) and social emotions (see Ross,
Homan, & Buck, 1994), or those that derive from attachment (e.g., love, shame).
There are several types of emotional behaviors including, autonomic-
endocrine-visceral and communicative (verbal-semantic, facial, prosodic, and
gestural-postural) with receptive and expressive components. Other dimensions
of emotion include emotional imagery and emotional memory.
The brain is critical for mediating emotional experiences and behavior. There-
fore, diseases that injure the brain may change both emotional experience and
behavior. In this chapter, we discuss how diseases of the brain may affect emo-
tional experience and emotional behavior. Diseases of the brain, like diseases in
other parts of the body, may induce an emotional response. In addition, there are
many diseases and conditions that can be induced or enhanced by emotional re-
367
368 CLINICAL IMPLICATIONS
sponses. Emotional response to diseases and emotionally induced diseases are

not, however, unique to neurological disorders and are not discussed in this
chapter.
The ideal chapter on how diseases of the brain affect emotional processes
would first discuss how the brain mediates emotions in normal subjects. Unfor-
tunately, the means by which the brain normally mediates emotion is not entirely
known, and much of what we know comes from studies of patients with neuro-
logical disorders. Recently, functional imaging has added to our understanding
of the role of the brain in emotions. There is also a rich literature on animal stud-
ies of emotional mediation. Unfortunately, it is unclear how much of this litera-
ture is relevant to the understanding of human emotion. Therefore, this chapter
focuses primarily on observations of humans, but occasionally we refer to ani-
mal studies.
Based on the work of Papez (1937), it has been thought that the limbic cir-
cuits play a very important role in the mediation of emotional experience. Al-
though subsequently many portions of the Papez circuit (e.g., hippocampus) have
been demonstrated to be important for processes such as memory, recent work
has demonstrated that other portions of the limbic system such as the amygdala
are important for emotions in humans. The cerebral cortex and basal ganglia also
play important roles. Many disorders of the basal ganglia, such as Parkinson's
disease, are associated with neurotransmitter defects. Neurotransmitters are crit-
ical for the activation and modulation of cortical and limbic systems. The frontal
lobes have strong connections not only with the limbic system and basal ganglia
but also with other areas of the cortex that may be important in mediating emo-
tions. Therefore, in addition to the posterior neocortex, the basal ganglia, por-
tions of the limbic system, and the frontal lobes play critical roles in emotions.
In this chapter, we discuss both the frontal and posterior neocortical, limbic, and
basal ganglia disorders that are associated with changes of emotional experience
or behavior, and based on these disorders, we discuss how the brain may medi-
ate emotional communication and experience.
CORTICAL DYSFUNCTION
Left Hemisphere Damage
Communication deficits
Comprehension. Developing an appropriate emotion depends, in part, on com-

munication with other people. Perhaps the two most important types of commu-
nication are speech and gestures, including facial expressions. Speech carries at
Neurological Disorders and Emotional Dysfunction 369
least two types of messages, prepositional and prosodic. Emotion can be con-
veyed by either words or prosody. The prepositional or linguistic content is con-
veyed by a complex code that requires an auditory or visual process, phonemic
or orthographic decoding, and lexical semantic analysis.
In most people, including left-handed people, the left hemisphere mediates
prepositional language. Therefore, injury particularly to the posterior portions of
the left hemisphere may impair the comprehension of prepositional speech. Pa-
tients with Wernicke's, transcortical sensory, global, or mixed transcortical apha-
sia may have difficulties in comprehending prepositional speech. Patients with
pure word deafness may also have problems understanding emotion that is based
on verbal-propositional speech. Often these aphasic syndromes are associated
with reading disorders or alexia. Alexia with or without aphasia may also impair
the comprehension of written material that can induce or communicate emotion.
Therefore, if the development of an appropriate emotional state depends on the
comprehension of either spoken or written propositional language, patients with
aphasia or alexia may be unable to develop the appropriate emotional state.
Although patients with comprehension disturbances may be unable to under-
stand propositional messages, many are still able to understand emotional into-
nations (prosody) and emotional facies (Barrett et al., 1997; Kanter et al., 1986).
When the propositional and prosodic messages are congruent, the addition of
emotional prosody may help aphasic patients understand the propositional mes-
sage (Bowers et al., 1987; Heilman, Scholes, & Watson, 1975).
Expression. Almost all patients with aphasia have problems expressing verbal-
propositional messages. Many patients with aphasia also have difficulty writing
their messages (agraphia). Agraphia, however, even in the absence of aphasia,
may also impair written expression of language. Therefore, if the communica-
tion of emotion depends on propositional language, individuals with aphasia and
agraphia may be impaired.
Hughlings Jackson (1932) noted that even severely, nonfluent aphasic patients
with left hemisphere lesions could express their emotion by intoning simple re-
current utterances with prosodic emotional intonations. In addition, when non-
fluent aphasic patients become angry or frustrated, it is not unusual for them to
express their emotional feelings by using explicatives. Hughlings Jackson (1932)
posited that perhaps it was the right hemisphere that was mediating these activ-
ities, and the role of the right hemisphere in expressing emotional intonations is
discussed later. Roeltgen, Sevush, and Heilman (1983) demonstrated that patients
with aphasia and agraphia could write emotional words better than nonemotional
words. Although it appears that the left hemisphere is dominant in propositional
speech, emotional words may be mediated by the right hemisphere and this will
also be discussed in a later section.
Emotional experience and mood

Goldstein (1948) noted that patients with left hemisphere lesions often demon-
strated an agitated or anxious depression. Goldstein called this emotional mood
the "catastrophic reaction." Gainotti (1972) replicated Goldstein's observations.
The catastrophic reaction is more likely to be seen with anterior than posterior
left hemisphere lesions (Benson, 1979; Robinson & Sztela, 1981). We discuss
the possible mechanisms of this mood change in a subsequent section.
Right Hemisphere Damage
Communication defects
Perceptual and comprehension disorders. As discussed, it appears that in most

right-handed and left-handed people it is the left hemisphere that mediates the
lexical-semantic processes important for speech. However, Borod and colleagues
(1992) presented emotional and nonemotional tasks that included word identifi-
cation, sentence identification, and word discrimination to right hemisphere-
damaged (RHD) patients, left hemisphere-damaged (LHD) patients, and con-
trols. They found that the RHD subjects were more impaired in the emotional
condition than the LHD patients or the controls.
Speech, however, can convey another message that, unlike the message con-
veyed by words, is conveyed by changes in prosody, including the amplitude,
pitch, timbre, and tonal contours of speech. During the last two to three decades
there have been multiple studies that suggest patients with right temporal pari-
etal damage have difficulty comprehending emotional prosody (Heilman,
Scholes, & Watson, 1975; Heilman et al., 1984; Ross, 1981). In addition, as pre-
viously discussed, there have also been reports of patients with severe word com-
prehension deficits associated with disorders such as pure word deafness (Kan-
ter et al., 1986) and global aphasia (Barrett et al., 1997), who, despite being
unable to understand words, have been able to understand emotional prosody,
thereby giving further support to the postulate that the right hemisphere has a
dominant role in the comprehension of emotional prosody.
The mechanism underlying this prosodic hemispheric asymmetry is not en-
tirely known. Patients with right hemisphere lesions, especially in the temporal
parietal regions, may be unable to discriminate (same or different) between var-
ious emotional prosodies, suggesting that the deficit is not one of denotation or
verbal-lexical labeling (Tucker, Watson, & Heilman, 1977). These findings sug-
gest that the right hemisphere contains emotional prosodic representations and
that these representations are stored in the right temporal parietal region. There-
fore, injury to these representations may impair the comprehension of emotional
prosody.
When involved in an emotional discussion with a significant other, we may

have been told, "It's not what you said, but how you said it." In such cases, the
prepositional word message and the emotional prosodic message may be incon-
gruent. When emotionally intoned sentences were presented to RHD and LHD
patients, comprehension of emotional prosody was more disrupted by incongru-
ent prepositional content for RHD patients, whereas comprehension of the prepo-
sitional content was more disrupted by the incongruent emotional prosody in
LHD subjects (Bowers et al., 1987).
Gestures such as facial expressions are also important in emotional commu-
nication and appropriate development of the emotional state. Repeated studies
have demonstrated that RHD patients are impaired in comprehending emotional
facial expressions (Borod et al., 1986; Bowers et al., 1985; Cicone, Wapner, &
Gardner, 1980; DeKosky et al., 1980; Schmitt, Hartje, Wilmes, 1997; Peper &
Irle, 1997). It has also been demonstrated that this deficit cannot be accounted
for by a purely lower level perceptual disorder (Blonder et al., 1993; Borod et
al., 1998; Bowers et al., 1987) or a higher order semantic-conceptual deficit
(Blonder et al., 1993). It is also not directly related to a face-processing deficit,
and perhaps the best explanation of the deficit seen with these patients is that
they have degraded emotional facial representations.
Support for this postulate comes from the observation that RHD subjects have
a defect in imagery for emotional faces but not objects. In contrast, subjects with
left-hemisphere disease have impaired imagery for objects but not emotional faces
(Bowers et al., 1991). Stimulation studies of epileptic patients suggest that these
emotional facial representations are stored in the posterior portion of the tempo-
ral lobe (Fried et al., 1982).
Expressive deficits. Bloom et al. (1990,1993) and Borod et al. (2000) studied emo-
tional and nonemotional discourse production, including the ability to use words to
convey emotion, in patients with right-hemisphere and left-hemisphere lesions as
well as normal controls. In the nonemotional condition, LHD subjects were partic-
ularly impaired, whereas in the emotional condition, RHD patients demonstrated
deficits. Emotional content facilitated the pragmatic performance of LHD subjects.
The speech of patients with right-hemisphere disease often lacks emotional
prosody (Ross, 1981; Tucker, Watson, & Heilman, 1977). This prosodic ex-
pressive deficit can be formally tested by asking patients to express neutral sen-
tences with different emotional prosodies. Expressive deficits can exist with and
without prosodic comprehension deficits (Ross & Mesulam, 1979). The patients
who appear to have expressive but not comprehension deficits often have lesions
in the anterior portions of the right hemisphere. Ross (1981) has suggested that
an expressive-receptive dichotomy of emotional prosody associated with right-
hemisphere lesions may parallel the manner in which the left-hemisphere lesions
disrupt the comprehension and expression of prepositional speech.
Patients with right-hemisphere dysfunction may have problems not only com-
prehending facial expressions but also expressing emotions using facial gestures.
This has been demonstrated both in the laboratory (Buck & Duffy, 1980) and in
natural situations (Blonder et al., 1993).
Emotional experience and mood

Patients with right cortical dysfunction may appear indifferent or even euphoric
(Babinski, 1914; Gainotti, 1972). There are several mechanisms that may account
for this profound indifference associated with right-hemisphere dysfunction. Al-
though communicative defects may partially account for the indifference asso-
ciated with right-hemisphere dysfunction, the changes in the mood associ-
ated with right-hemisphere dysfunction are included in the later discussion of
mechanisms.
Emotional memory
To learn if patients with hemispheric dysfunction have specific problems with
the acquisition of emotional memories or anterograde emotional memory deficits,
Wechsler (1973) presented two stories to patients with right-hemisphere and left-
hemisphere strokes. One story was designed to elicit an emotional response, and
the other story contained little or no emotion. Whereas the patients with left-
hemisphere lesions recalled more from the emotion-charged story than from the
emotion-neutral story, the patients with right-hemisphere disease did not detect
any difference between the stories, thereby suggesting that the emotional aspects
of the story did not benefit their memory.
To study retrograde emotional memory deficits, Cimino and coworkers (1988)
asked patients to tell stories about events that happened to them in the past. These
stories were then given to judges who assessed the emotional content. These
judges found that RHD patients' stories had less emotional content than did those
of LHD patients. Borod et al. (1996) also studied recall of subjects' positive and
negative emotional experiences and nonemotional experiences. Judges thought
that the experiences described by the RHD subjects had less emotional intensity
than those described by the LHD or normal subjects.
Somewhat different findings have been described by Bowers et al. (1998) who
also examined the emotionality of autobiographical memories recalled by pa-
tients with focal hemispheric strokes. In that study, there was no explicit demand
that subjects describe emotional memories per se. Rather, subjects were instructed
merely to recall personal memories associated with specific cues words (i.e., the
Crovitz paradigm). Content ratings by blinded judges revealed no overall differ-
ences in the types of emotional topics (e.g., weddings, death, and illness) cov-
ered by the stroke groups. The memories of the LHD group were, however, less
intensely positive than were those of the RHD or control groups. There were no
group differences in the intensity of negative memories. Because there was no
evidence of depression according to various mood scales, it is difficult to at-

tribute these valence asymmetries to the presence of depression per se. To ac-
count for these findings, one could posit that left-hemisphere lesions may alter
the retrieval of information from semantic networks that are uniquely concerned
with pleasant events. Lesions of the left hemisphere either directly hamper this
process or create a mood bias whereby such networks are not readily primed.
The neuropsychological mechanisms accounting for the emotional anterograde
and retrograde deficits described above remain unknown. One possibility is that
the subjects with right-hemisphere disease have an expressive deficit. Although
recall in these studies depended on propositional speech, as discussed above, pa-
tients with right-hemisphere disease may be impaired at expressing emotions even
when using words. A second possibility is related to mood. When testing mem-
ory, subjects generally perform better with recognition than recall. Recognition
paradigms provide subjects with cues that help activate the neural nets that store
these memories. Depressed subjects will better recall sad than happy events (Yang
& Rehm, 1993). This phenomenon has been termed mood congruence. Mood
congruence may be a special form of cuing. Subjects with right-hemisphere le-
sions may perform poorer with emotional memory tests because they have a flat-
tened affect, and emotional memories would be incongruent with their mood.
Bilateral Frontal Cortical Dysfunction
Neurological disorders can induce injuries to both sides of the brain. For exam-
ple, trauma and tumors can injure both frontal lobes. Vascular diseases, espe-
cially of the anterior cerebral artery, may also induce bilateral lesions of the
frontal lobes. Bilateral frontal lobe dysfunction may have profound effects on
emotional behavior and experience. There have been many important case re-
ports of patients who had bilateral frontal lobe lesions and had profound changes
of emotional behavior and responses. These cases include the famous Gage de-
scribed by Harlow (1868), Patient A described by Brickner (1934, 1936), and
Ackerly and Benton's case along with the cases reported by Damasio and An-
derson (1993). In general, these patients suffered with emotional indifference
and apathy unless frustrated, when they would often become inappropriately
aggressive.
There have been several studies with positron emission tomography (PET) of
subjects with a history of aggressive behavior and violence (e.g., murderers). The
studies revealed reduced activity in the frontal lobes (Raine et al., 1994; Volkow
et al., 1995).
Normal people avoid stimuli or situations that have been know to produce
emotions with negative valence (e.g., fear, anger, sadness, disgust) and to ap-
proach stimuli or situations that induce emotions of positive valence. Bilateral
disorders of the frontal lobe may interfere with this process. Damasio and An-
derson (1993) suggest that the response selection impairment is due to a "defect
in the activation of somatic markers . . . that mark the ultimate consequences of
the response option with a negative or positive somatic state." They also indi-
cate that the frontal lobes are critical for this process and suggest that the orbital
and lower mesial frontal regions may be the most important portion of the frontal
lobes.
Corticobulbar Dysfunction
Bilateral dysfunction of the corticobulbar pathways may induce a pseudobulbar

palsy. Associated with this pseudobulbar palsy may be involuntary emotional ex-
pressions. These abnormal emotional expressions are stereotypical and do not
show degrees of intensity or a spectrum of emotional expressions. Usually, pa-
tients with pseudobulbar palsy either laugh, cry, or both. The latter is very sim-
ilar to the cry of an infant who, even in the absence of neocortex, may cry. When
patients express these emotions, however, they often are not experiencing the
emotion that they are expressing.
It has been posited that bilateral interruption of the corticobulbar pathways re-
lease or disinhibit subcortical centers that mediate these emotional behaviors.
Wilson (1924) suggested that this subcortical center was in the region of the pons,
and Poeck (1969) suggested that these expressions are programmed in the dien-
cephalon (hypothalamus and thalamus). Sackeim et al. (1982) noted that, although
patients with pseudobulbar emotional expressions had bilateral lesions, those with
larger left-hemisphere lesions were more likely to cry and those with right-sided
lesions were more likely to laugh.
LIMBIC SYSTEM DYSFUNCTION
Emotional Communication
Unlike dysfunction of the cerebral cortex, emotional communication disorders

are not frequently encountered with limbic dysfunction. Adolphs et al. (1994),
however, described a woman who had bilateral damage to the amygdala and a
concomitant disturbance in the processing of faces expressing fear. Although
Young et al. (1995) found that identification of facial emotion was disturbed in
their patient D.R. after partial bilateral amygdala ablation, other aspects of face
processing were also impaired, including recognition of familiar faces and de-
tection of direction of gaze on faces. Adolphs et al. (1994) also demonstrated
that unilateral amygdala damage did not interfere with the processing of fearful
faces and that bilateral lesions were necessary. In line with this observation, Bow-
ers and colleagues (1999) examined 26 patients after anterior temporal resections
involving approximately 45%-55% of the volume of the right or left amygdala.

Relative to controls, these patients had no difficulty processing emotional faces,
fearful or otherwise. These findings reinforce the view that unilateral amygdala
lesions are not sufficient to disrupt the networks involved in the detection of
fear/threat from nonverbal social signals.
Functional imaging studies in normal subjects have also provided converging
evidence that the amygdala is important in the processing of fearful faces (Bre-
iter et al., 1996; Irwin et al., 1996; Phillips et al., 1997). Amygdala activation
has even been demonstrated with functional magnetic resonance imaging (fMRI)
under conditions in which subjects are unaware that fearful faces have been briefly
shown (Whalen et al., 1998). In this study, faces depicting fear or happiness were
presented for 33 msec and were then immediately followed by masking stimuli
consisting of neutral faces. Although the masking procedure inhibited subject's
overt awareness of having viewed an emotional face, it nevertheless did not in-
terfere with a process via which fearful, but not happy, faces differentially acti-
vated the amygdala.
Some evidence suggests that the amygdala's role in processing affective dis-
plays of fear or anger is not modality specific (Scott et al., 1997). Scott and
coworkers (1997) examined their patient (D.R.) who had partial bilateral amyg-
dala damage. Not only was this patient impaired at recognizing facial expres-
sions of fear and anger (see Young et al., 1995), she was also impaired at rec-
ognizing vocal intonation patterns (prosody) associated with fear and anger. No
hearing deficits existed to account for this prosody perception defect. Other in-
vestigators have reported disturbances in the recognition of nonverbal fear sig-
nals that may be modality specific. Ghika-Schmid et al. (1997) described a pa-
tient with bihippocampal damage (left more than right) whose recognition of
vocal expressions of fear was selectively disrupted relative to other types of emo-
tional prosody. The perception of fear faces was intact, although perception of
other facial expressions was severely impaired (e.g., contempt, surprise).
Before final conclusions can be made about modality or category specificity
of emotional processing, it is crucial to verify that comparable levels of diffi-
culty existed among various facial and/or intonational emotion stimuli, both
within and across modalities. Regarding prosody, it is equally important to ex-
amine a full range of auditory processing abilities, from basic acoustic to lin-
guistic prosody tasks.
Emotional Experience
Paul Broca (1878) called a group of anatomically related structures on the me-
dial wall of the cerebral hemispheres "le grand lobe limbique." Papez (1937)
thought that a circuit in this limbic lobe that included the cingulate gyrus, hip-
pocampus, fornix, mammillary bodies, and anterior thalamus was a core com-
ponent of the central mechanisms subserving emotional feeling and expression.

In part, Papez's postulate about the limbic system came from the knowledge that
the hypothalamus was important in mediating rage responses (Bard, 1934). Sub-
sequent studies have, however, revealed that lesions in several areas of the Pa-
pez circuit are associated with memory rather than emotional deficits.
Yakovlev (1948) posited that another brain circuit may be an important ele-
ment of the limbic system. This basal lateral circuit includes the orbital frontal
and insular cortex, the uncinate fasciculus, the anterior temporal cortex, the amyg-
dala, and the dorsomedial nucleus of the thalamus. Kluver and Bucy (1937)
demonstrated that bilateral ablation of the anterior temporal lobe, which inter-
rupts this basal lateral limbic circuit of Yakovlev, changed aggressive rhesus
monkeys into tame and placid animals. Akert et al. (1961) demonstrated that it
was not the removal of temporal lobe cortex but rather of the amygdala that in-
duced this lameness. Subsequent studies revealed that amygdala stimulation in-
duced rage and that specific ablation induced placidity (Ursin, 1960; Woods,
1956). Investigators also demonstrated that the amygdala was important for fear,
and a series of studies performed by Davis (1989) and LeDoux (1993) demon-
strated that the amygdala was critical for fear conditioning.
Animal studies revealed that whereas septal lesions can cause a rage-like state
(Brady & Nauta, 1955), septal stimulation can induce an extremely positive emo-
tion (Olds, 1958). Some of the emotional changes described in animals with sep-
tal and amygdala lesions and stimulation have also been observed in humans.
Tumors of the septal region in humans have been reported to cause rage-like at-
tacks with increased irritability and agitation (Poeck & Pilleri, 1961; Zeman &
King, 1958). In contrast, stimulation of the septal region has been reported to be
pleasant and even sexually arousing (Heath, 1964). Bilateral temporal lesions in
humans that included the amygdala have been reported to reduce rage and to in-
duce placidity (Poeck, 1969). Morris and coworkers (1991) demonstrated that re-
moval of the right amygdala reduces the experience and autonomic nervous
system-visceral response to stimuli that before ablation induced emotions of neg-
ative valence. The experience and response to stimuli that induced emotions with
positive valence was unchanged.
Viral and inflammatory diseases, such as herpes simplex, rabies, and limbic
encephalitis may destroy portions of the limbic system and thus may be associ-
ated with many abnormal emotional behaviors, including depression, agitation,
and anxiety. It is difficult to ascertain exactly how these diseases induce emo-
tional changes.
Partial seizures with complex symptoms, also called temporal lobe epilepsy or
psychomotor seizures, often start in limbic structures. These seizures may be as-
sociated with emotional symptoms. Emotional changes may be seen during a
seizure. Mood changes may also be seen in epileptics even between seizures (the
so-called interictal phenomenon). Gascon and Lombrosco (1971) described pa-
tients with temporal lobe seizures who laughed as part of their epileptic phe-
nomena (gelastic seizures). All of Gascon and Lombrosco's patients had right-
sided seizures. Chen and Forster (1973) described 10 patients who had gelastic
seizures, but seven of the ten had left-sided seizures. Alternatively, some patients
may cry during seizures. This is called dacrystic epilepsy. Unfortunately, these
cases are so rare that clear lateralization has not been demonstrated. Offen et al.
(1976) reviewed six patients with dacrystic epilepsy; four had right temporal dys-
function, one had left-sided dysfunction, and in one the locus was unknown.
The relationship between epilepsy and aggression remains unclear. Mark and
Erwin (1970) and Pincus (1980) think that there is a relationship between tem-
poral lobe epilepsy and aggression, but Stevens and Hermann (1981) note that
there are no well-controlled studies to support this relationship. Of all the emo-
tions reported with seizures, fear is the emotion most frequently reported
(Williams, 1956). Ictal fear has been reported with both right and left temporal
seizure foci (Strauss, Risser, & Jones, 1982). Within the temporal lobe, when
fear is associated with a seizure, the amygdala appears to be the critical struc-
ture (Glore, 1972). Interictal abnormalities of mood appear to be frequently as-
sociated with patients who have temporal lobe epilepsy. The most common ab-
normalities appear to be anxiety and depression. Men with left-sided foci appear
to have more fear than those with right-sided foci (Strauss, Risser, & Jones, 1982).
In addition, patients with temporal lobe epilepsy seem to have a higher incidence
of attempted or successful suicide than control subjects (Hawton, Fagg, & Mar-
sack, 1980). Flor-Henry (1969) and Bear and Fedio (1977) demonstrated that in-
terictally, patients with right hemisphere foci are more likely to show emotional
changes such as sadness or elation.
Interictal aggressiveness, like aggressiveness during a seizure, remains con-
troversial and continues to be a source of many medicolegal arguments. Although
Taylor (1959) reported that temporal epileptics had a higher incidence of inter-
ictal aggression, Stevens and Hermann (1981), as previously discussed, noted
that these observations have not been validated by detailed, controlled studies
BASAL GANGLIA DISEASES
Disorders of the basal ganglia are commonly thought to primarily induce de-
fects in motor performance. Basal ganglia disorders are, however, known to af-
fect both emotional experience and emotional communication. In some cases,
the emotional changes associated with basal ganglia diseases can even precede
the motor symptoms (e.g., Huntington's disease). In this section we review
some of the emotional experiences and communicative changes associated with
diseases of the basal ganglia and discuss the possible pathophysiologies of these
changes.
Parkinson's Disease
Emotional communication
Facial expressions. One of the core symptoms of Parkinson's disease (PD) is

the expressionless or "masked" face. Neurologists have long distinguished be-
tween disorders of volitional facial expression that result from lesions to the mo-
tor strip or corticobulbar projections and those of spontaneous facial expression
that result from subcortical lesions, particularly those involving the basal gan-
glia. Thus, it has been observed that PD patients are able to make facial expres-
sions to command but that spontaneous facial expression tends to be "flat" (Rinn,
1984). Two recent studies have, however, found diminished emotional facial ex-
pressivity even during posed conditions, suggesting that both systems are affected
by PD (Borod et al., 1990; Jacobs et al., 1995a). Lack of facial expressivity is
not thought to reflect depressed mood, as lack of expressivity is more prevalent
than dysphoria among PD patients (Rinn, 1984). Furthermore, in two studies of
spontaneous facial expressions, there was no correlation between depression
scores and facial expressivity scores, again suggesting that diminished facial ex-
pressivity is not simply a function of depressed mood (Katsikitis & Pilowsky,
1991; Smith, Smith, & Ellgring, 1996).
Clinical observations of masked facies in PD patients have been confirmed by
experimental studies. Buck and Duffy (1980) videotaped PD, LHD, and RHD
patients and normal controls while each participant viewed a set of emotionally
evocative slides. Raters then watched the videotapes and rated the subjects' emo-
tional expressivity on a seven point scale. Results showed that RHD and PD pa-
tients were rated as significantly less expressive than LHD aphasics and normal
controls.
Scott, Caird, and Williams (1984) found deficits in PD patients' ability to pro-
duce facial expressions of anger. Brozgold et al. (1998) found that PD patients
showed significantly greater negative affect than controls while relating an un-
pleasant experience, yet were deficient in expressing positive affect while con-
veying a pleasant experience. Katsikitis and Pilowski (1988, 1991) used a mi-
crocomputer program to quantify facial expressions of PD patients who had
observed a series of amusing slides. They found that PD patients smiled less fre-
quently than did controls. Pitcairn et al. (1990) showed that PD patients produced
a greater proportion of false smiles (smiles lacking a cheek raise) than did
controls.
Smith, Smith, and Ellgring (1996) used the Facial Action Coding system
developed by Ekman and Friesen (1978) to analyze both spontaneous and
posed facial expressions. They found that PD patients displayed less emotional
reactivity to emotionally laden film clips than did the normal control group.
Furthermore, in moderately affected PD patients, the intensity of spontaneous

smiles was lower than the intensity of posed smiles. The findings of Smith,
Smith, and Ellgring (1996) corroborate those of Pitcairn and collaborators
(1990) in that the PD group produced fewer true or "felt" smiles than did the
controls during the spontaneous condition. This loss of facial expressivity was
not associated with diminished capacity to experience emotion, as Smith and
colleagues found that patient ratings of subjective emotion experienced in re-
sponse to the video clips were comparable, if not more intense, than ratings
by controls.
Studies have also shown that PD patients are impaired in the perception of
emotional facial expressions, although these results are less consistent. Blonder,
Gur, and Gur (1989) found that PD patients could name or match facial emo-
tions as well as the control group. When facial identity recognition versus facial
emotion recognition were compared within the PD group, however, the investi-
gators found that PD patients made significantly more errors in the emotional
than in the nonemotional task. Within the controls, the two face tasks were per-
formed comparably. Scott, Caird, and Williams (1984) found deficits in the abil-
ity of PD patients to recognize angry facial expressions. Jacobs et al. (1995b)
discovered impairments in the ability to discriminate facial emotion among non-
demented PD patients.
Prosody. A second channel of nonverbal communication of emotion that has

received considerable attention over the last few decades is prosody, mainly in-
tonation, stress, and timing. Disorders of prosody, particularly monopitch and
loss of volume in the voice, are characteristic of parkinsonian speech. These find-
ings have been observed both clinically and experimentally. For example, Dar-
ley, Aronson, and Brown (1969) performed a judgment study of speech charac-
teristics in PD and found that monopitch, monoloudness, and increased rate were
among the most pronounced prosodic abnormalities. Acoustic analyses of parkin-
sonian speech have also found evidence of monotone production (Canter, 1963;
Kent & Rosenbek, 1982).
Many consider that speech disorders in PD are related to defects of motor pro-
graming. Prosodic disturbances in PD may, however, have an emotional dimen-
sion. Scott, Caird, and Williams (1984) found that PD patients had difficulty pro-
ducing anger through prosody. Blonder, Gur, and Gur (1989) found that PD
patients' ability to convey different emotions through prosody was judged to be
impaired, and the intensity of their emotional prosody was also rated as less ex-
pressive than that of normal controls. Similar results were found by Borod et al.
(1990). This evidence supports the idea that parkinsonian prosody compromises
patients' ability to express emotion through the voice. Scott, Caird, and Williams
(1984), Blonder, Gur, and Gur (1989), and Borod et al. (1990) found that PD pa-
tients were also impaired in their ability to comprehend emotion conveyed

through prosodic intonations.
Emotional experience
Although PD is characterized by akinesia, a resting tremor, and rigidity, Parkin-
son (1817) noted that his patients were often unhappy. There are now many re-
ports in the literature documenting depression in patients with PD (Brown et al.,
1988; Gotham, Brown, & Marsden, 1986; Liu et al., 1997; Mayeux et al., 1981,
1984; Vogel, 1982; for review, see Cummings, 1992). Cummings (1992) esti-
mates that depression occurs in approximately 40% of PD patients. Of those,
about half have major depression.
Some studies suggest that depression in PD patients may have a reactive com-
ponent. As discussed by Lindgren (1996), PD is associated with continual loss
of function during the illness that can affect not only patients but also their
spouses, producing states of "chronic sorrow." Gotham, Brown, and Marsden
(1986) compared PD patients, arthritis sufferers, and normal controls on mea-
sures of depression and found that both the PD patients and the arthritis suffer-
ers were depressed. In addition, depression in both patient groups was similar in
that it was characterized by pessimism, hopelessness, decreased motivation, and
increased concerns regarding health. Despite these data, the bulk of the evidence
indicates that depression in PD is most likely due to depletion of brain cate-
cholamines and serotonin, dysregulation of frontal subcortical connections in-
volved in emotion regulation, or a combination these processes.
The depression associated with PD is atypical. Schiffer et al. (1988) applied Re-
search Diagnostic Criteria to 16 depressed PD patients and 20 depressed patients with
multiple sclerosis and found that the depression in the PD patients was often ac-
companied by anxiety and panic. Stein et al. (1990) found that 38% of the PD pa-
tients in their sample of 24 met Diagnostic and Statistical Manual of Mental Disor-
ders, third edition, revised (DSM-ffl-R), criteria for a diagnosis of a concurrent anxiety
disorder. This rate exceeds that found in the general population as well as in indi-
viduals with chronic medical conditions. These authors also note that there were no
differences in disease severity between the anxious PD patients and those who lacked
anxiety disorders, suggesting that anxiety is not simply a reaction to disability.
As discussed earlier with regard to cortical dysfunction, whereas patients with
left hemisphere disease are often depressed, those with right hemisphere dys-
function are often indifferent or even euphoric. Several studies have examined the
relationship between mood and laterality of parkinsonian motor symptoms. Nei-
ther Barber et al. (1985), Blonder, Gur, and Gur (1989), nor St. Clair et al. (1998)
found differences in self-reported depression between right and left hemiparkin-
son patients. Fleminger (1991), however, showed that symptoms of atypical de-
pression (i.e., depression with relatively little anhedonia and prominent anxiety)
were increased fivefold in patients with left hemiparkinsonism, suggesting right
basal ganglia dysfunction. Fleminger's finding is contradicted in a study by Stark-

stein et al. (1988), who found depression following left but not right basal gan-
glia infarcts. This finding is also inconsistent with the reports of emotional changes
associated with cortical dysfunction that we previously discussed.
One problem associated with the diagnosis of depression in patients with PD
is that many instruments used to measure depression confound the symptoms of
physical illness and normal aging with those of dysphoria. For example, the Beck
Depression Inventory, reported by Cummings (1992) to be the instrument most
widely used to measure depression in PD patients, includes both somatic and
ideational items. When Direnfield et al. (1984) excluded items associated with
neurologic symptomatology from the Beck Depression Inventory, they found that
PD patients, those suffering from Alzheimer's disease, and hospitalized controls
exhibited no differences in dysphoria. In a study by Blonder, Gur, and Gur (1989),
PD patients' scores on the Zung Depression Inventory were significantly higher
(more depressed) than those of age-matched controls when somatic indicators
were included. When these items were excluded, there were no statistically sig-
nificant between-group differences. In contrast, Levin, Llabre, and Weiner (1988)
performed internal consistency reliability analyses of the Beck Depression In-
ventory in 119 PD patients and 76 controls and found that the instrument was a
valid measure of dysphoric mood in the PD patients.
From a neuropharmacological perspective, it is not surprising that PD patients
show symptoms of dysphoria. It is well documented that these patients have de-
pletion of brain norepinephrine and serotonin (Scatton et al., 1983). Norepi-
nephrine and serotonin were initially implicated as etiological agents in depres-
sive mood when hypertensive patients receiving reserpine therapy developed
dysphoria (Lemieux, Davignon, & Genest, 1956). Reserpine acts by depleting
central and peripheral norepinephrine and serotonin. Chan-Palay and Assan
(1989) found extensive cell loss in the rostral and caudal portions of the locus
coeruleus of depressed PD patients while those who had not been depressed
showed relative sparing of caudal neurons. These findings implicate noradrener-
gic systems in the etiology of parkinsonian depression. The involvement of these
neurotransmitters in mood is further substantiated by the therapeutic efficacy of
monoamine oxidase inhibitors, tricyclic compounds, and selective serotonin re-
uptake inhibitors (SSRIs) in the treatment of depression associated with PD.
Several studies have evaluated the effects of levodopa on patients' mood and
yielded somewhat inconsistent findings (see Mayeux, 1983). Spigset and von Scheele
(1997) reported two patients who increased their own dosage of levodopa to
1500-2000 mg/day to induce feelings of euphoria. Maricle et al. (1995) found that
mood elevation, anxiety reduction, and a corresponding increase in tapping speed
were related to levodopa but not to placebo infusion in a sample of PD patients.
Price, Farley, and Hornykiewicz (1978) showed that PD patients have signifi-
cantly reduced levels of dopamine in the limbic paraolfactory gyrus and the nu-
cleus accumbens. These levels correlate with the amount of dopamine reduction in
the neostriatum. There is also evidence that the dopaminergic innervation of these
limbic structures may be anatomically related to the nigrostriatal fiber system. In-
vestigators have proposed that degeneration of dopaminergic terminals in the ven-
tral tegmental region underlies parkinsonian mood disorders, and interindividual
differences in the extent to which this system is involved may explain variability
in the incidence of depression in PD (Cantello et al., 1989). How changes in neu-
rotransmitter systems induce changes in mood, however, remains to be determined.
Huntington's Disease
Published studies of facial processing in patients with Huntington's disease (HD)
are limited to perception. Jacobs et al. (1995b) administered tests of emotional and
nonemotional facial perception to five patients with HD and found impaired per-
formance. They suggest that these deficits may be related to degeneration of the
tail of the caudate in HD. Sprengelmeyer et al. (1996) found that HD patients were
impaired in the recognition of surprised, fearful, sad, angry, and disgusted facial
expressions, with severe deficits in the recognition of disgust. They attribute this
profound impairment in disgust recognition to HD-associated atrophy in paleo-
cortical regions, including the periamygdalar and pyriform cortex. More recently,
Phillips et al. (1997) showed fMRI activation of the anterior insula during the per-
ception of disgusted faces by normal individuals. This region is connected to a lim-
bic-striatal-thalamic ckcuit. This finding may explain the loss of recognition of
disgust by HD patients. The amygdala is known to atrophy in HD and, as discussed
with regard to the limbic system, this region has been associated with the pro-
cessing of emotional facial expressions. Emotional prosody has not been fully stud-
ied in patients with HD. Speedie et al. (1990), however, reported that patients with
HD were also impaired in the comprehension of prosodic signals.
Huntington's disease or Huntington's chorea is characterized by involuntary
dance-like movements and intellectual decline. Huntington (1872) reported that
many patients with this disease have emotional disorders and that there was a high
rate of suicide associated with the disorder. Emotional dysfunction is highly preva-
lent in HD. Mayeux (1983) estimates that most if not all patients with HD manifest
some type of emotional disorder, including apathy or irritability, depression, manic-
depression, agitation, hostility, aggression, promiscuity, and suicidal behavior (see
also Brothers, 1964; Folstein, Folstein, & McHugh, 1979; Mayberg et al., 1992;
Mayeux et al., 1981). Emotional changes may precede the motor or cognitive symp-
toms, suggesting that cerebral dysfunction and not reactive disorders is responsible
(Heathfield, 1967; Kosky, 1981). In addition, different emotional symptoms may be

seen during different stages of the disease. Apathy usually occurs late in the disease
when there are intellectual deterioration and signs of frontal lobe dysfunction.
When Mayberg et al. (1992) measured regional cerebral glucose metabolism
in depressed and nondepressed HD patients and normal controls, they found that
both groups of HD patients had reductions in caudate, putamen, and cingulate
metabolism. The depressed HD patients were distinguished from their nonde-
pressed counterparts by orbital-frontal-inferior prefrontal hypometabolism, im-
plicating paralimbic frontal regions in mood disturbance. This pattern has also
been observed in depressed PD patients (Mayberg et al., 1990).
Ranen et al. (1996) noted complete cessation of severe irritability and aggres-
sion in two HD patients after treatment with an SSRI. SSRIs, as well as tricyclic
antidepressants, have been used to treat depression in HD. Bipolar disorders and
apathy have also been treated with lithium and butyrophenone. Although neuro-
transmitters such as gamma-aminobutyric acid and acetylcholine are reduced in
the basal ganglia, the mechanisms underlying the mood changes associated with
this disease remain unknown.
Progressive Supranuclear Palsy
Patients with progressive supranuclear palsey (PSP) have akinesia and axial rigid-
ity similar to that seen with PD. These patients do not, however, have a resting
tremor, but do have supranuclear palsies of their cranial nerves. For example,
PSP, patients may be impaired in looking up or down to command. When the
head is rapidly flexed and extended, however, the eye may then move up and
down (ocular cephalic reflex).
When Steele, Richardson, and Olszewski (1964) first reported this disorder, they
noted that their patients were often irritable. Like other patients with diseases that
involve the basal ganglia, however, patients with PSP may also have apathy and
depression. Litvan et al. (1996) examined emotional disorders in 22 patients with
PSP, and found that 91% exhibited apathy, 18% dysphoria, and 18% anxiety.
Menza, Cocchiola, and Golbe (1995) found that 42% of the PSP patients suffered
from mild depression or anxiety and that these rates were comparable to those
found in the PD group. Both cognitive and functional imaging studies of PSP pa-
tients show evidence of frontal lobe dysfunction (Blin et al., 1990; Grafman et al.,
1990). Litvan et al. (1996) attribute the high incidence of apathy in their sample
of PSP patients to dysfunction in the medial frontal/subcortical system.
Wilson's Disease
Wilson's disease (WD) is principally characterized by neuropathological

changes in the putamen and globus pallidus, although other structures are also
affected. Patients with WD may exhibit tremors, athetoid movements, and

dysarthria. A significant proportion of patients with WD are reported to have
emotional disturbances, including depression, anxiety, aggression, and person-
ality changes (Dening & Berrios 1989; Rathbun, 1996; Sternleib & Scheinberg,
1964). In Rathbun's series (1996), 50% of the WD patients had been hospital-
ized for psychiatric disorders before they were diagnosed with WD, reaffirm-
ing the importance of thorough neurological and medical examinations of pa-
tients with psychiatric disorders. Dening and Berrios (1989) found a correlation
between psychiatric and neurological symptoms but not between psychiatric
and hepatic symptoms, suggesting that the emotional changes accompanying
WD are primarily related to brain dysfunction and not a psychological reac-
tion to their disease.
Striatonigral Degeneration
Garcia-Campayo and Sanz-Carrillo (1994) reviewed the scant literature on psy-

chiatric disorders accompanying Striatonigral degeneration (SND), a syndrome
that resembles PD but usually is not associated with tremor and responds less
well to the dopaminergic medication than do patients with PD. Neuropathologi-
cally, SND is characterized by neuronal loss in the putamen, globus pallidus, and
substantia nigra. Previous published reports of mood changes associated with this
disorder include depression (Bannister & Oppenheimer, 1972; Fearnley & Lees,
1990; Feve et al., 1977), anxiety (Scully, Mark, & McNeely, 1983), and emo-
tional lability (Fearnley & Lees, 1990).
Garcia-Campayo and Sanz-Carrillo (1994) reported a patient who initially pre-
sented with major depression with no neurologic symptoms or signs. The de-
pression was successfully treated with imipramine. Several months later, the pa-
tient developed an unsteady gait and suffered repeated falls and a recurrence of
depression. Neurological examination revealed extrapyramidal motor symptoms,
and an MRI scan showed putamenal atrophy. The diagnosis of SND was con-
firmed 2 years later when the patient came to autopsy. Garcia-Campayo and Sanz-
Carrillo (1994) suggest that, as in PD, dysfunction in neurotransmitter systems
involved in mood regulation may lead to emotional disturbance in SND.
Other Basal Ganglia Disorders
Cancelliere and Kertesz (1990) mapped cerebral infarcts on CT scans and found
that most individuals with deficits in the comprehension of facial affect had sus-
tained damage to the basal ganglia and the anterior temporal lobe, suggesting
basal ganglia involvement in facial affect perception.
Sydenham' s chorea, which may be seen with diseases such as rheumatic fever
and systemic lupus, may also be associated with irritability and apathy. Trautner
et al. (1988) report affective disorders in five patients with idiopathic basal gan-
glia calcification. Four of the five patients had unipolar depression, whereas the
fifth was described as hypomanic. They also review previous reports of mood
disorders in patients with calcification of the basal ganglia.
Starkstein et al. (1988) compared mood in stroke patients whose infarcts were
confined to either the left or right basal ganglia or to the left or right thalamus
and found that the patients with left-sided lesions of the basal ganglia had a higher
frequency and severity of depression than did any of the other groups. Seven of
eight patients with left-sided basal ganglia lesions showed major depression,
whereas only one of seven patients with right-sided basal ganglia lesions had ma-
jor depression. Furthermore, none of the patients with restricted thalamic lesions
showed major depression.
Affective Disorders and Basal Ganglia Dysfunction
There have been several studies of basal ganglia function in patients with pri-
mary affective disorders. For example, some investigators have shown reductions
in putamenal or caudate volumes in patients who suffer from major depression
(Husain et al., 1991; Krishnan et al., 1992). Figiel et al. (1991) found a higher
number of caudate hyperintensities in patients with late onset unipolar depres-
sion than in patients with early onset unipolar depression. These subjects had no
past history of any disease associated with subcortical structural changes on MRI.
Results from studies of basal ganglia dysfunction in patients with bipolar dis-
order are inconsistent. Swayze et al. (1992) did not find differences in caudate
or putamenal volumes between bipolar subjects and normal controls. Aylward et
al. (1994) found that males with bipolar disorder had larger caudate volumes than
did normal control males. Sharma et al. (1992) examined patients with bipolar
disorder who were being treated with lithium. Proton magnetic resonance spec-
troscopy showed changes in the metabolite ratios in the basal ganglia spectra.
These findings may have been due to either the action of lithium or the rela-
tionship of bipolar disorder itself and basal ganglia dysfunction.
POSSIBLE MECHANISMS OF EMOTIONAL

COMMUNICATION DISORDERS
Studies of patients with left-hemisphere dysfunction have demonstrated that their

verbal lexicon (auditory word images) and semantics (meaning) are dissociable.
Whereas the left hemisphere contains a verbal lexicon and verbal semantics, per-
haps the right hemisphere contains prototypic facial iconic and prosodic echoic
emotional representations, as well as emotional semantics. To test this postulate,
Blonder, Bowers, and Heilman (1991) examined subjects with right-hemisphere
and left-hemisphere damage by presenting them with sentences, generated by a
computer, that described either an emotional gesture (e.g., emotional face) or a
scene that may induce an emotion (e.g., the children tracked mud all over new
white carpet). Compared with both left-hemisphere damage and control subjects,
the subjects with right-hemisphere damage did well noting the emotion associ-
ated with the description of scenes that was designed to test their emotional se-
mantics. In contrast, the subjects with right-hemisphere damage performed poorly
in recognizing the description of emotional gestures. These results cannot be ex-
plained by a visuospatial defect because the stimuli were verbal. These results
suggest an iconic representational defect.
Further evidence that RHD subjects have an emotional facial iconic defect
comes from a study by Bowers et al. (1991). If patients have lost their repre-
sentations of prototypic emotional facial expressions, they should not only fail
to recognize emotional faces and be unable to recognize descriptions of emo-
tional faces but they also should not be able to image emotional faces. Bowers
et al. (1991) demonstrated that RHD subjects could image objects, but they could
not image emotional faces. In contrast, LHD subjects could image emotional
faces but not objects.
Although we presented evidence that the representations of emotional faces
may be stored in a sensory-iconic form, there is an alternative possibility. When
subjects are asked that when they use a screw driver to remove a screw, do they
rotate their arm in a clockwise or a counterclockwise direction, most subjects re-
port that when they attempted to answer this question they had to covertly move
their arm. Functional imaging studies have also demonstrated that when subjects
are asked to think about making a movement without actually making the move-
ment, their premotor cortex demonstrates activation.
Patients with PD often have mask-like faces and often do not spontaneously
express facial emotions. To test this motor representational hypothesis, we stud-
ied PD patients' ability to image and comprehend emotional faces. Compared
with control subjects, patients with PD were impaired (Jacobs et al., 1995a).
These observations suggest that to comprehend or image an emotional face, one
may have to activate motor representations.
Patients with emotional face discrimination and comprehension defects often
have coexisting problems in discriminating and comprehending emotional
prosody. It has been estimated that approximately 40%-45% of RHD patients
are impaired on both face and prosody affect tasks versus 22% of LHD patients
(Bowers et al., 1996). Dissociations between the ability to perceive facial affect
versus the ability to perceive emotional prosody have been clinically described
(Ross, 1981). To determine the frequency of modality-specific disturbances in a
large population, Bowers et al. (1996) examined 105 patients with MRI-verified
ischemic hemispheric lesions using the Florida Affect Battery. This battery con-
sists of facial, prosodic, and cross-modal tasks designed to identify general and
specific subtypes of affect disturbance (modality-specific, anomic, and agnosic
variants). Approximately 22% of the RHD patients were uniquely impaired on
face perception tasks versus 2% of the left hemisphere group. Of note, relatively
few patients were found to have an "isolated" prosody perception defect, and the
lesions in these "pure cases" included ones in the insula and temporal region.
Taken together, these observations suggest that prosodic and facial emotional
representations are, in part, independent.
Darwin believed that the means by which we express emotions are innate. If
the facial expression of emotion is innate, there should be little or no difference
in emotional expression across cultures. To learn if the expression of emotion is
innate, Izard (1977) and Ekman, Sorenson, and Freisen (1969) performed cross-
cultural studies of facial emotional expression and found that the same seven to
nine emotional facial expressions appeared to be universal, thereby providing
support for Darwin's hypothesis that emotional expressions are innate. There-
fore, unlike the left hemisphere's phonological or orthographic lexicon, which is
culturally specific and therefore learned, the right hemisphere's emotional rep-
resentations may be primarily inborn rather than learned.
POSSIBLE MECHANISMS OF EMOTIONAL EXPERIENCE
As discussed earlier, dysfunction of the cortex, limbic system, and basal ganglia
induces changes in emotional experience and mood. In this section we explore
the possible mechanisms. We briefly review the classic feedback and central the-
ories and the more recent revisions of these theories. Then, based on the changes
in emotional experience and mood associated with neurological disorders, we at-
tempt to develop a model of how the brain mediates emotional experience.
Feedback Theories
Facial feedback hypothesis

Darwin (1872) noted that, "He who gives violent gesture increases his rage."
Tomkins (1962, 1963) posited that it was the feedback of these facial emotions
to the brain that induced emotional feeling. Many of the patients we discussed
who have right-hemisphere dysfunction have a reduced ability to express facial
emotions and also are emotionally indifferent, thereby providing some support
to the facial feedback hypothesis. Laird (1974) experimentally manipulated fa-
cial expressions and found that subjects felt emotions, providing support for the
facial feedback hypothesis. There are, however, many unresolved problems with
the facial feedback theory of emotional experience.
One of the major problems is that it is, at least in part, circular. If facial feed-
back induces emotional experience, what induces facial emotion? Second, we re-
cently had the opportunity to examine and test a young woman who had
Guillian-Barre syndrome. This is a neuropathy that can affect the cranial nerves.
During her disease, the patient had total facial paralysis. When presented with a
set of standardized slides that have been shown to evoke emotional experience
and responses in normal subjects (Greenwald, Cook, & Lang, 1989), this woman's
emotional responses were the same as those of the controls. After she recovered
full facial mobility she was tested again, and her emotional experiences to these
slides were unchanged from her previous test results (Keillor et al., 1999). Also
unsupportive of the facial feedback hypothesis of emotional experience is the ob-
servation that patients with pseudobulbar palsy may express strong facial emo-
tions that they are not feeling (Poeck, 1969). It is possible, however, that these
patients' brain lesions also interrupt facial feedback to the brain. As we discussed,
patients with PD and parkinsonian symptoms may have a mask-like face but feel
sad and depressed.
Visceral feedback hypotheses

William James (1890) proposed that stimuli that provoke emotion induce
changes in the viscera and autonomic nervous system and that it is the self-
perception of these visceral changes that produces emotional experience. To have
visceral feedback, one needs efferent and afferent systems. The autonomic ner-
vous system has two components, the sympathetic and parasympathetic. The de-
scending sympathetic neurons receive projections from the hypothalamus, and
the hypothalamus receives projections from many limbic and paralimbic areas,
including the amygdala. The most important parasympathetic nerve is the vagus.
The vagus originates in the dorsal motor nucleus situated in the brain stem and
projects to the viscera such as the heart. The amygdala not only projects to the
hypothalamus but also sends direct projections to the nucleus of the solitary tract
and the dorsal motor nucleus of the vagus. In this manner, the amygdala may di-
rectly influence the parasympathetic system. The amygdala receives neocortical
input. Although the amygdala may be the most important part of the limbic sys-
tem to influence autonomic nervous system and viscera, stimulation of other ar-
eas, including the insula and orbitofrontal cortex, can also induce autonomic and
visceral changes, and these structures also receive input from the neocortex.
With regard to feedback, the major nerve that carries visceral afferent infor-
mation back to the brain is the vagus. These afferents terminate in the nucleus of
the solitary tract, which projects to the central nucleus of the amygdala. The cen-
tral nucleus of the amygdala projects to other amygdala nuclei and the insula. The
amygdala and insula, in turn, project to the temporal, parietal, and frontal lobes.
As we discussed above, in humans the neocortex and limbic cortex plays a

critical role in the analysis and interpretation of various stimuli. Luria and Simer-
nitskaya (1977) thought that the right hemisphere may be more important than
the left in perceiving visceral changes. James' feedback theory was challenged
by Cannon (1927), who thought that the viscera have insufficient afferent input
to the brain to be important in inducing emotional experience. Using a heartbeat
detection paradigm, Katkin et al. (1982) found that normal subjects can accu-
rately detect their heartbeat. They also reported that the subjects who had the
strongest emotional responses to negative slides were the subjects who were best
able to detect their own heartbeat (Hantas, Katkin, & Blasovich, 1982).
Cannon (1927) also argued that the separation of the viscera from the brain
that occurs with cervical spinal cord injuries does not eliminate emotional ex-
perience. Hohmann (1966), however, studied patients with spinal cord injuries
at different levels and found that patients with either high or low spinal cord
transection did experience emotions, but patients with lower lesions reported
stronger emotions than those with higher lesions. Higher cervical lesions would
be more likely to affect efferent control of the viscera and injure the auto-
nomic nervous system's afferent output. Therefore, Hohmann's observations
provide partial support for the visceral feedback theory. Cannon (1927) thought
that because the same visceral responses occur with different emotions, feed-
back of these visceral responses could not account for the variety of emotions
that humans experience. Ax (1953) and others have, however, demonstrated
that different visceral-autonomic reactions are associated with different emo-
tions.
Although many of Cannon's objections (1927) to the visceral feedback theory
could be refuted, there are still observations that are inconsistent with this the-
ory. Maranon (1924) injected epinephrine into normal subjects. Epinephrine does
not cross the blood-brain barrier but does affect the autonomic nervous system
and viscera, inducing increased activity of the heart. After the injection with
visceral-autonomic activation, Maranon inquired as to the nature of the emotion
felt by these subjects and found that injections of epinephrine were not associ-
ated with emotional experience but rather with "as if feelings.
Because visceral-autonomic activation, by itself, did not induce an emotional
experience, Schacter and Singer (1962) posited that another element is needed
to induce emotions. Schachter and Singer (1962) also injected epinephrine into
experimental subjects and reported that pharmacologically induced autonomic
and visceral activation did not, by itself, produce an emotion. When this injec-
tion with visceral-autonomic activation was accompanied with an appropriate
cognitive set, however, an emotion could be induced. Some cognitive sets may,
by themselves, produce an emotion. Schacter and Singer (1962), however, found
that the emotion induced by a cognitive set was stronger in the subjects who re-
ceived epinephrine than in those who did not receive epinephrine.
Although Schachter and Singer's study (1962) suggested that visceral feed-
back together with centrally mediated cognition are important for emotional ex-
perience, observations in our laboratory do not entirely support these findings.
Recently, we attempted to further test the autonomic-visceral feedback theory
and to learn if, as suggested by Luria and Simernitskaya (1977), the right hemi-
sphere plays a dominant role in perceiving visceral changes. Using a shock an-
ticipation paradigm in brain-lesioned subjects, we found that, compared with
normal control subjects, patients with right-hemisphere lesions had a reduced au-
tonomic response. Although their autonomic response was reduced, they showed
no differences in the experience of anticipatory anxiety (Slomine, 1995). In ad-
dition, in the clinic one can see patients who have strong emotions (e.g., fear)
associated with medial temporal lobe or amygdala seizures. Sometimes patients
become aware that they are beginning to have a seizure, and the fear of having
a seizure may lead to a fearful cognitive set. Autonomic and visceral changes
may be associated with these partial seizures, and the patients may be aware of
these changes and therefore experience fear. In many epileptic patients, however,
the emotional experience is often the first symptom or aura. Therefore, in these
patients, cognitive set comes after the experience rather than before the experi-
ence. Schachter and Singer's attribution theory (1962) cannot account for these
observations.
The studies we have discussed do not preclude the possibility that visceral and
facial feedback play some role in emotional experience. Although feedback may
influence emotional experience, the evidence we reviewed suggests that feed-
back does not play a critical role in emotional experience. In addition, the feed-
back theories cannot explain the mood changes induced by neurological diseases.
Central Theories
Subcortical (diencephalic) theories

To account for emotional experience, Walter Cannon (1927) proposed that af-
ferent stimuli enter the brain and are transmitted from the thalamus to the hypo-
thalamus. The hypothalamus activates the endocrine and autonomic nervous sys-
tem, and it is these systems that induce the physiological changes in the viscera.
These autonomic and visceral changes are primarily adaptive and aid in the sur-
vival of the organism. Emotional experience is induced by the hypothalamus
feeding back to the cortex.
LeDoux and coworkers (1990) have modified Cannon's (1927) thalamic-hy-
pothalamic emotion circuit to include the amygdala in fear conditioning. These
investigators conditioned animals by associating a nociceptive stimulus with an
auditory stimulus. Although ablation of the auditory thalamus and amygdala in-
terrupted the behavioral emotional response to the conditioned stimulus, ablation
of the auditory cortex did not. Therefore, LeDoux et al. (1990), like Cannon
(1927), do not propose a critical role for the cortex in the interpretation of stim-
uli in the mediation of emotional experience. Whereas conditioned stimuli sim
ilar to those used by LeDoux et al. (1990) may induce emotion without cortical
interpretation, as we discussed, there is overwhelming evidence that in humans
the neocortex is critical for interpreting the meaning of many stimuli that induce
an emotional experience. The diencephalic-hypothalamic theory of Cannon
(1927) and the diencephalic-limbic (amygdala) theory of LeDoux et al. (1990)
also fail to explain how humans can experience a variety of emotions.
Modular theory
There are at least two ways in which the brain may mediate a variety of emo-
tional experiences. One possibility is that the brain may contain specialized or
devoted emotional systems for each emotional experience such that each emo-
tion is uniquely mediated. Therefore, there would be a special system for fear,
anger, happiness, and so forth. A second possibility is that each emotion is not
uniquely mediated but that the neural apparatus that mediates one emotion may
not only play a role in other emotions but also mediate nonemotional functions.
The second or nondevoted systems postulate is consistent with the "dimen-
sional" view of emotion. Wundt (1903) proposed that emotional experiences vary
in three dimensions, quality, activity, and excitement (arousal). Osgood, Suci,
and Tannenbaum (1957) performed factor analyses on verbal assessments of emo-
tional judgements and found that the variance could be accounted for by three
major dimensions: valence (positive/negative, pleasant/unpleasant), arousal
(calm/excited), and control or dominance (in control/out of control). Using this
type of multidimensional view, one can define the different emotional experi-
ences by using one or more of these three dimensions. For example, fear would
be unpleasant; high arousal, out of control; and sadness could be unpleasant and
low arousal. Psychophysiological studies with normal subjects have supported
this dimensional view (Greenwald, Cook, & Lang, 1989). Frijda (1987) also ex-
plored the cognitive structure of emotion and found that "action readiness" was
an important component or dimension.
Heilman (1994, 1997) posited that conscious experience of emotion may be
mediated by anatomically distributed modular networks. This distributed network
has three major modules: one that helps determine the valence, a second that con-
trols arousal, and a third that mediates motor activation with either approach or
avoidance behaviors.
Valence. In prior sections we discussed the studies that demonstrated that

whereas people with left-hemisphere lesions are often sad and anxious, those
with right-hemisphere lesions often appear indifferent or euphoric. Gainotti
(1972) proposed that patients' psychological response to their own illness may
account for some of the emotional asymmetries observed between patients with
right-hemisphere and left-hemisphere lesions. Whereas patients with left-hemi-
sphere disease are often aphasic and have a hemiparesis of their preferred hand,
those with right-hemisphere damage often are unaware of their disabilities
(anosognosia). Other observations are not, however, consistent with this reaction
postulate.
Terzian (1964) and Rossi and Rosadini (1967) studied the emotional reactions
of patients recovering from selective hemispheric barbiturate-induced anesthesia
(the Wada test). These investigators noted that whereas barbiturate injections into
the left carotid artery were often associated with catastrophic reactions, injec-
tions into the right hemisphere were associated with indifference or euphoria.
Because the Wada test is a diagnostic study that only causes transient hemiparesis
and aphasia, it is unlikely that it would cause a reactive depression. In addition,
we have seen RHD stroke patients who are emotionally indifferent but who are
aware of their deficits and do not demonstrate anosognosia or verbally explicit
denial of illness.
The catastrophic-depressive reaction associated with left-hemisphere lesions
is seen most commonly in patients who have anterior (frontal) perisylvian lesions
(Benson, 1979; Robinson & Sztela 1981). It is possible that the hemispheric emo-
tional asymmetries reported by Gainotti (1972) and others are related to emo-
tional communication disorders associated with frontal lesions, as discussed
earlier, rather than differences in emotional experience. Although defects in emo-
tional expression may account for some of the behavioral observations by Gold-
stein (1948), Babinski (1914), and Gainotti (1972), they cannot explain the re-
sults of Gasparrini et al. (1978), who administered the Minnesota Multiphasic
Inventory to a group of LHD and RHD patients. The LHD patients were not se-
verely aphasic, and the RHD and LHD patients were balanced for cognitive and
motor defects. The Minnesota Multiphasic Inventory does not require emotion-
ally intoned speech or facial expressions. Gasparrini et al. (1978) found that
whereas patients with left-hemisphere disease showed a marked elevation of the
depression scale, patients with right-hemisphere disease did not. Therefore, the
right-left differences in emotional behavior observed by Gainotti (1972) and oth-
ers cannot be attributed to emotional expressive disorders or to severity of the
motor or cognitive deficit.
Starkstein, Robinson, and Price (1987) also studied emotional changes asso-
ciated with stroke and found that about one third of stroke patients had depres-
sion. They found that depression was associated with both left frontal and left
caudate lesions and also that the closer to the frontal pole the lesion was located,
the more severe the depression. Many of the patients with left-hemisphere le-
sions and depression were also anxious. In contrast, patients with right frontal
lesions were often indifferent or even euphoric. Not all investigators agree, how-
ever, that after stroke there is more depression with left-hemisphere than with
right-hemisphere lesions. House et al. (1990) and Milner (1974) could not repli-
cate the emotional symmetries found in other reports.
To learn if there are discrete physiological changes of the brain associated with
depression, several groups of investigators studied patients with primary depres-
sion using functional imaging. Several of these investigators noted a decrease in
activation in the left frontal lobe as well as in the left cingulate gyrus (Bench et
al., 1992; Phelps et al., 1984). Drevets and Raichle (1992), however, found in-
creased activity in the left prefrontal cortex, amygdala, basal ganglia, and thala-
mus.
Davidson et al. (1979) and Tucker (1981) investigated the hemispheric valence
hypothesis by studying normal subjects using electrophysiological techniques and
confirmed the results of the ablation studies. Unfortunately, it is not known how
the right and left hemisphere may influence emotional valence. Fox and David-
son (1984) suggest that left hemisphere-mediated positive emotions are related
to approach behaviors and that right hemisphere-mediated negative emotions are
related to avoidance behaviors. In our laboratory, we studied emotions and ap-
proach-avoidance behavior. We found that negative emotions can be associated
with both approach and avoidance behaviors (Crucian et al., 1997). For exam-
ple, fear and anger both have a negative valence, but fear is associated with avoid-
ance and anger approach. In addition, this approach-avoidance model does not
explain how the two hemispheres are differently organized such that they make
opposite contributions to mood or how other emotions are mediated, nor does it
explain the role of other areas in the brain such as the basal ganglia and limbic
system.
With regard to the limbic system, the amygdala, which is critical for negative
emotions such as fear and anger, when bilaterally ablated, induces a reduction in
the experience of these emotions. To learn if the right amygdala may be more
important than the left in mediating emotions with negative valence, Morris and
coworkers (1991) showed slides with positive and negative valence to a subject
before and after temporal lobectomy. This study demonstrated that ablation of
the right anterior temporal lobe, which included the amygdala, reduced the pa-
tient's experience of negative emotions.
Tucker and Williamson (1984) think that hemispheric valence asymmetries
may be related to asymmetrical control of neuropharmacological systems, with
the left hemisphere being more cholinergic and dopaminergic than the right hemi-
sphere, and the right hemisphere being more noradrenergic than the left hemi-
sphere. Robinson and Starkstein (1989) reported that pharmacological changes
in the two hemispheres may be different after stroke. They reported that strokes
in the right hemisphere appear on PET images to increase serotonergic receptor
binding and that left-hemisphere strokes lower serotonergic binding. The lower
the serotonergic binding, the more severe the depression. Although it is well
known from clinical psychiatry that neurotransmitter systems may have a pro-
found influence on mood, the mechanism by which the pharmacological changes

induce mood remain unknown. In addition, as we discussed above, moods and
emotions may not be synonymous and may be mediated differently.
Arousal. Arousal has both behavioral and physiological components. Behav-

iorally, an aroused organism is awake, alert, and prepared to process stimuli. An
unaroused organism is lethargic to comatose and not prepared to process stimuli.
Physiologically, arousal has several definitions. In the central nervous system,
arousal usually refers to the excitatory state of neurons or to the propensity of
neurons to discharge when appropriately activated. In functional imaging, arousal
is usually measured by increases of blood flow, and electrophysiologically, it is
measured by desynchronization of the EEC or by the amplitude and latency of
evoked potentials. Outside the central nervous system, arousal usually refers to
activation of the sympathetic nervous system and the viscera such as the heart.
Arousal and attention are intimately linked and appear to be mediated by a
modular cortical limbic reticular network (Heilman, 1979; Mesulam, 1981; Wat-
son, Valenstein, & Heilman, 1981). An overview of this network is presented
here, but for details one should refer to the original articles or, for a review, see
Heilman, Watson, and Valenstein (1993b).
Much of what we know about the anatomical basis of this network initially
came from studies of monkeys and patients with discrete brain lesions. More re-
cently, functional imaging has confirmed much of the ablation research. In hu-
mans, lesions of the inferior parietal lobe are most often associated with disor-
ders of attention and arousal (Critchley, 1966; Heilman, Valenstein, & Watson,
1983). In monkeys, temporoparietal ablations are also associated with attentional
disorders (Heilman, Pandya, & Geschwind, 1970; Lynch, 1980). Physiological
recordings from neurons in the parietal lobes of monkeys appear to support the
postulate that the parietal lobe is important in attention. Unlike neurons in pri-
mary sensory cortex, the rate of firing of these "attentional" neurons in the pari-
etal lobe appears to be associated with the significance of the stimulus to the
monkey such that relevant stimuli are associated with higher firing rates than are
unimportant stimuli (see Bushnell, Goldberg, & Robinson, 1981; Lynch, 1980).
Sensory information projects to the thalamic relay nuclei. From the thalamus,
these modality-specific sensory systems project to the primary sensory cortices.
Each of these primary sensory cortices (e.g., visual, tactile, auditory) projects
only to its associated cortex. For example, Brodmann's area 17, the primary
visual cortex, projects to Brodmann's area 18. Subsequently, each of these modal-
ity-specific association areas converges on polymodal areas such as the frontal
cortex (periarcuate, prearcuate, and orbitofrontal), and both banks of the supe-
rior temporal sulcus (Pandya & Kuypers, 1969). Both of these latter sensory poly-
modal convergence areas project to the supramodal inferior parietal lobe (Mesu-
lam et al., 1977).
Whereas the determination of stimulus novelty may be mediated by modality-

specific sensory association cortex, stimulus significance requires knowledge as
to both the meaning of the stimulus and the motivational state of the organism.
The motivational state depends on at least two factors: immediate biological needs
and long-term goals. It has been demonstrated that portions of the limbic system
together with the hypothalamus monitor the internal milieu and develop drive
states. Therefore, limbic input into regions important in determining stimulus sig-
nificance may provide information about immediate biological needs. Portions
of the limbic system such as the cingulate gyrus, project to both the inferior pari-
etal lobe and the frontal lobe. Regarding long-term goals, the frontal lobe has
been demonstrated to play a major role in goal-oriented behavior and set devel-
opment (Damasio & Anderson, 1993; Stuss & Benson, 1986). Frontal input into
the attentional-arousal systems may provide information about goals that are not
motivated by immediate biological needs. Studies of cortical connectivity in mon-
keys have demonstrated that the temporoparietal region has strong connections
not only with portions of the limbic system (i.e., cingulate gyrus) but also with
the frontal cortex.
Stimulation of the mesencephalic reticular formation (MRF) in animals in-
duces behavioral and physiological arousal (Moruzzi & Magoun, 1949). In con-
trast, bilateral lesions of the MRF induce coma, and unilateral lesions cause the
ipsilateral hemisphere to be both behaviorally and physiologically hypoaroused
(Watson et al., 1974). The polymodal and supramodal cortical areas we discussed
above not only determine stimulus significance but also modulate arousal by in-
fluencing the MRF (Segundo, Naguet, & Buser, 1955). The exact means by which
these cortical areas influence the MRF and the MRF influences the cortex re-
main unknown.
There are, however, at least three possible mechanisms by which the MRF
may influence cortical processing. Shute and Lewis (1967) describe an ascend-
ing cholinergic reticular formation. The nucleus basalis, which is in the basal
forebrain, receives input from the reticular formation and has cholinergic pro-
jections to the entire cortex. These cholinergic projections appear to be impor-
tant for increasing neuronal sensitivity (Sato et al., 1987). The MRF may also
influence the cortical activity through thalamic projections. Steriade and Glenn
(1982) demonstrated that nonspecific thalamic nuclei, such as centralis lateralis
and paracentralis, project to widespread cortical regions and that these thalamic
nuclei can be activated by stimulation of the mesencephalic reticular formation.
The third mechanism that may help account for cortical arousal involves the thal-
amic nucleus reticularis. This thin nucleus envelops the thalamus and projects to
all the sensory thalamic relay nuclei. Physiologically, the nucleus reticularis in-
hibits the thalamic relay of sensory information (Scheibel & Scheibel, 1966).
When cortical limbic networks determine that a stimulus is significant or novel,
however, corticofugal projections may inhibit the inhibitory nucleus reticularis,
thereby allowing the thalamic sensory nuclei to relay sensory information to the
cortex.
The level of activity of the peripheral autonomic nervous system usually mir-
rors the level of arousal in the central nervous system. One means of measuring
peripheral autonomic arousal is by assessing hand sweating. When the hand
sweats, there is a change in resistance. To learn if there were differences in the
hemispheric control of sweating, Heilman, Schwartz, and Watson (1978) stud-
ied RHD and LHD patients and normal controls. These subjects received noci-
ceptive stimuli (electric shock) that was uncomfortable but not painful. The RHD
patients had a reduced arousal response compared with controls and LHD pa-
tients. Subsequently, other investigators also reported similar findings.
For example, Morrow et al. (1981) and Schrandt, Tranel, and Damasio (1989)
also found that RHD patients had a reduced skin response to emotional stimuli.
There was, however, another interesting finding. Compared with normal subjects,
LHD patients appeared to have a greater autonomic response (Heilman, Schwartz,
& Watson, 1978). Using changes in heart rate as a measure of arousal, Yokoyama
et al. (1987) obtained results similar to those with galvanic skin response. Using
functional imaging, Perani et al. (1993) also found that, in patients with right
hemisphere stroke, there is also a metabolic depression of the left hemisphere.
Unfortunately, LHD control patients were not included.
The mechanisms underlying the asymmetrical hemispheric control of arousal
remain unknown. Because lesions restricted to the right hemisphere were not
found to directly interfere with the left hemisphere's corticofugal projections to
the reticular system or the reticular system's corticopetal influence on the left
hemisphere, one could propose that the right hemisphere's control of arousal may
be related to privileged communication that the right hemisphere has with the
reticular activating system. Alternatively, portions of the right hemisphere may
play a dominant role in computing stimulus significance. The increased arousal
associated with left-hemisphere lesions also remains unexplained. Perhaps the
left hemisphere maintains some type of inhibitory control over the right hemi-
sphere or the reticular activating system.
Motor activation and approach-avoidance. Some emotions do not call for action
(e.g., sadness, satisfaction), but others do (e.g., anger, fear, joy, surprise). When
emotions are associated with action, this action may be toward the stimulus (ap-
proach) or away from the stimulus (avoidance) that induced the emotion. People
want to avoid emotions that are unpleasant and approach situations that induce
pleasant emotions, but this is not what we are addressing when we discuss ap-
proach and avoidance. Rather, we are addressing the behavior associated with
the emotion and not the plans for structuring the behavior in relation to the stim-
uli that induce the emotions. For example, whereas one would like to avoid sit-
uations that induce anger, when one does become angry, one has a propensity to
approach the stimulus that is inducing this emotion. Joy, a positive emotion, is
also associated with approach behaviors.
Primbram and McGuiness (1975) use the term activation to denote the phys-
iological readiness to respond to stimuli. We have posited that motor activation
or motor intention is mediated by a modular network that includes portions of
the cerebral cortex, basal ganglia, and limbic system (for a detailed review, see
Heilman, Bowers, & Valenstein, 1993a; Heilman & Watson, 1989). The dorso-
lateral frontal lobe appears to be a critical portion of this motor preparatory net-
work (Heilman, 1978; Watson, Miller, & Watson, Valenstein, & Heilman, 1981).
Physiological recordings from cells in the dorsolateral frontal lobe reveal neu-
rons that have enhanced activity when the animal is presented with a stimulus
that is meaningful and predicts movement (Goldberg & Bushnell, 1981).
The dorsolateral frontal lobe receives input from the cingulate gyrus and from
posterior cortical association areas that are modality specific, polymodal, and
supramodal. Input from these posterior neocortical areas may provide the frontal
lobe information about the stimulus, including its meaning and its spatial loca-
tion. The limbic system (e.g., the cingulate gyrus, which is not only part of the
Papez circuit but also receives input from Yakolov's basal lateral circuit) may
provide information as to the organism's motivational state. The dorsolateral
frontal lobe has nonreciprocal connections with the basal ganglia (e.g., caudate),
which in turn projects to the globus pallidus, and the globus pallidus projects to
the thalamus, which projects back to the frontal cortex (Alexander, DeLong, &
Strick, 1986).
The dorsolateral frontal lobe also has extensive connections with the nonspe-
cific intralammar nuclei of the thalamus (centromedian and parafasicularis).
These intralaminar nuclei, which can be activated by the mesencephalic reticu-
lar system, may gate motor activation by their influence on the basal ganglia, es-
pecially the putamen, or by influencing the thalamic portion of motor circuits
(ventralis lateralis pars oralis). Finally, the dorsolateral frontal lobe has strong
input into the premotor areas. The observation that lesions of the dorsolateral
frontal lobe, the cingulate gyrus, the basal ganglia, the intralaminar nuclei, and
the ventrolateral thalamus may all cause akinesia supports the postulate that this
system mediates motor activation.
The right hemisphere appears to play a special role in motor activation or in-
tention. Coslett and Heilman (1989) demonstrated that right-hemisphere lesions are
more likely to be associated with contralateral akinesia than are those of the left
hemisphere. Howes and Boiler (1975) measured reaction times (a measure of the
time taken to initiate a response) of the hand ipsilateral to a hemispheric lesion and
demonstrated that right-hemisphere lesions were associated with slower reaction
times than were left-hemisphere lesions. As previously discussed, however, this
finding may be related to the important role of the right hemisphere in mediating
attention and arousal. Heilman and Van Den Abell (1979) measured the reduction
in reaction times of normal subjects who received warning stimuli directed to

either their right or left hemisphere. They found that, independent of the hand
used, the warning stimuli delivered to the right hemisphere reduced reaction
times to midline stimuli more than warning stimuli delivered to the left hemi-
sphere.
Whereas some emotions (e.g., anger and joy) are associated with approach be-
haviors, other emotions (e.g., fear and disgust) are associated with avoidance be-
haviors. Unfortunately, the portions of the brain that mediate approach and avoid-
ance behaviors have not been entirely elucidated. Denny-Brown and Chambers
(1958) suggested that the frontal lobes mediate avoidance behaviors and the pari-
etal lobes mediate approach behaviors. Denny-Brown and Chambers (1958) also
suggested that approach and avoidance behaviors may be reciprocal such that a
loss of one behavior may release the other behavior. Therefore, because the frontal
lobes mediate avoidance behavior, frontal lobe lesions would cause inappropri-
ate approach behaviors, and because the parietal lobes mediate approach behav-
iors, parietal lesions would induce avoidance. In support of this postulate are
those patients with frontal lesions who demonstrate a variety of approach be-
haviors, including manual grasp reflexes, visual grasp reflexes, rooting and suck-
ing responses, magnetic apraxia, utilization behaviors, and defective response in-
hibition. Unfortunately, the specific area or areas within the frontal lobes that
when damaged cause approach behaviors have not been entirely elucidated. An-
imals with frontal lesions show an increase in aggressive behavior. Patients with
left dorsolateral frontal lesions (which should induce an emotion of negative va-
lence, increased arousal, and approach behaviors) are also prone to hostility and
anger (Grafman et al., 1986).
Denny-Brown and Chambers (1958) demonstrated that, in contrast to the man-
ual grasp response associated with frontal lesions, patients with parietal lesions
may demonstrate a palmar avoiding response. Patients with parietal lesions, es-
pecially of the right side, may not only fail to move or have a delay in moving
their arms, head, and eyes toward a part of space that is opposite the parietal le-
sion, but may also deviate their eyes, head, and arms toward ipsilateral hemi-
space. In addition, unlike patients with frontal lesions who cannot withhold their
response to stimuli, patients with parietal lesions may not be able to respond to
stimuli (neglect). These avoidance responses are more severe with right-
hemisphere than with left-hemisphere lesions.
SUMMARY
Emotions may be divided into two major divisions, experience and behavior. Be-
cause the brain is critical for mediating emotional experience and behavior, dis-
eases of the brain may induce changes in emotional behavior and experience.
Disorders of almost all portions of the cerebral hemisphere, including the cor-
tex, limbic system, and basal ganglia, have been associated with changes in emo-
tional experience and behavior. Dysfunction of the cerebral cortex may be asso-
ciated with disorders of emotional communication. Whereas deficits of the left
hemisphere appear to impair the comprehension and expression of prepositional
language, deficits of the right hemisphere may be associated with an impaired
ability to comprehend and express emotional gestures, such as facial expressions
and emotional prosody. Some patients have either prosodic or facial emotional
deficits. Some have only expressive or receptive deficits. Others, however, may
be globally impaired either within or across modalities. The posterior portions
of the neocortex appear to be important for comprehension, and the anterior por-
tions seem to be important for expression of both emotional prosody and facial
gestures.
Injury and dysfunction of the limbic system may also alter emotional com-
munication and experience. For example, amygdala damage may be associated
with an impaired ability to recognize emotional faces and with a reduction of af-
fect, especially anger, rage, and fear. In contrast, lesions of the septal region may
be associated with increased rage-like behaviors. Seizures frequently emanate
from the limbic system, and seizures that start in the amygdala can induce fear
and perhaps even rage.
Disorders of the basal ganglia may also be associated with defects of emo-
tional communication and, experience. Patients with PD may not only be im-
paired in communicating emotions, showing both expressive and receptive
deficits, but also are often depressed and anxious. Patients with HD may have
emotional comprehension deficits with an impaired ability to recognize emotional
faces and prosody. Patients with HD may also have mood changes even before
their motor dysfunction becomes manifest.
Many of the defects in emotional experience may be related to the associated
changes in neurotransmitter systems. Unfortunately, how alteration of neuro-
transmitters induces mood changes remains unknown.
In this chapter, we review the feedback and central theories of emotional ex-
perience. Although we argue against the postulate that feedback is critical to the
experience of emotions, we do suspect that feedback may influence emotions.
Emotions may be conditioned and may use thalamic-limbic circuits. Most emo-
tional behaviors and experiences are, however, induced by complex stimuli that
an isolated thalamus could not interpret.
The cerebral cortex of humans has complex modular systems that analyze stim-
uli, develop percepts, and interpret meaning. We discuss the proposal that the
experience of emotions is dimensional. Almost all primary emotions can be de-
scribed with two or three factors, including valence, arousal, and motor activa-
tion. The determination of valence is based on whether the stimulus is beneficial
(positive) or detrimental (negative) to a person's well being. Whereas the right
frontal lobe and its subcortical connections appear to be important in the medi-
ation of emotions with negative valence, the left frontal lobe and its subcortical
connections may be important in the mediation of emotions with positive va-
lence. Depending on the nature of the stimulus, some positive and some nega-
tive emotions are associated with high arousal (e.g., joy and fear) and others with
low arousal (e.g., satisfaction and sadness). Whereas the right parietal lobe ap-
pears to be important in mediating the arousal response, the left hemisphere ap-
pears to inhibit the arousal response. Some positive and negative emotions (e.g.,
anger, fear, and joy) are associated with motor activation and others (e.g., sad-
ness) are not. The right frontal lobe appears to be important in motor activation.
The motor activation associated with emotions may be either approach or avoid-
ance behaviors. Whereas approach behaviors may be mediated by the parietal
lobes, avoidance behaviors may be mediated by the frontal lobes.
The cortical areas we have discussed have rich connections. In addition, these
neocortical areas also contain rich connections with the limbic system, basal gan-
glia, thalamus, and reticular system. Therefore, the anatomic modules that me-
diate valence, arousal, and activation systems are richly interconnected and form
a modular network. Emotional experience depends on the patterns of neural ac-
tivation of this modular network, and the neurotransmitter systems that are al-
tered in many neurological diseases may play a critical role in altering the pat-
terns of activation.
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16
Rehabilitation of Emotional Deficits
in Neurological Populations:
A Multidisciplinary Perspective
SARAH A. RASKIN, RONALD L BLOOM,

AND JOAN C. BOROD
Traditionally, pharmacological intervention and psychotherapy have been the pre-

dominant approaches for the treatment of emotional disorders. This chapter focuses
on the treatment of affect rather than on therapy designed to adjust or alter mood.
Techniques from a variety of disciplines are discussed to provide a framework for
the treatment of emotional deficits in patients with neurological disorders.
The chapter begins by exploring different approaches to clinical management,
including cognitive rehabilitation, speech-language rehabilitation, and numerous
psychotherapeutic strategies. Techniques from these various approaches are ap-
plied to the assessment and treatment of emotional processing deficits. Next, a
brief overview of the emotional deficits associated with selected neurological dis-
orders (i.e., traumatic brain injury, stroke, Parkinson's disease, senile dementia
of the Alzheimer's type, and multiple sclerosis) is provided. For an in-depth dis-
cussion, see Heilman et al. (Chapter 15, this volume).
Based on the model of fundamental emotional responses conceptualized in Part
II of this volume, specific treatment strategies are proposed for depression, anx-
iety/stress, anger/irritability, apathy/indifference, and impaired affect. Detailed
descriptions of these emotional disorders are given elsewhere in this volume. In
this chapter, processes that underlie cognition, language, and speech, and their
relationships to emotional processing, are discussed, and the need for a multi-
disciplinary approach to rehabilitation is emphasized.
413
CONTEMPORARY REHABILITATION
Approaches to Rehabilitation
We begin with a review of cognitive and speech-language rehabilitation techniques.

These techniques provide a basis for the treatment of emotional disorders.
Cognitive rehabilitation and speech-language therapy

Cognitive rehabilitation or remediation is a form of intervention in which a
series of procedures are applied by a trained practitioner to retrain or alleviate
problems in a person's daily life due to deficits in cognitive functions (e.g.,
Sohlberg & Mateer, 1989). There are many theoretical models that support dif-
ferent types of cognitive rehabilitation currently in practice (e.g., Diller & Gor-
don, 1981; Sohlberg & Mateer, 1989). Similarly, speech-language therapy is a
systematic approach to rehabilitation that emphasizes restoration of an individ-
ual's communication abilities. There are numerous theories that attempt to ex-
plain the relationships among brain, language, and behavior (Goodglass & Ka-
plan, 1983) and theoretical models that support a host of techniques designed to
assist recovery of speech (Duffy, 1995) and language (Chapey, 1986).
Clinical models are still needed to form the basis of emotional rehabilitation,
but models of emotional processing (e.g., Borod, 1993b) can provide a basis for
intervention. In general, models of rehabilitation can be divided into two basic
approaches: functional skills training and process-oriented rehabilitation. Both
approaches have implications for the rehabilitation of emotional deficits in neu-
rological populations.
Functional skills training. Functional skills training involves retraining specific

skills of daily life, most often in a particular living or work environment. The
skill to be retrained is broken down into component parts; the underlying cog-
nitive requirements of the skill or task are not examined (Mayer, Keating, &
Rapp, 1986). Generalization to other contexts is not a goal of treatment (Kirsch,
Levine, & Fallon-Krueger, 1987). Although the targeting of specific tasks en-
countered in the individual's daily life can appear to have considerable ecologi-
cal validity, the narrow focus and restricted generalizability may limit the po-
tential for recovery. Practical limitations on the number of skills that can be
targeted and trained make this approach less relevant for many patients. For ex-
ample, in terms of emotional processing, one could train specific skills such as
smiling when given a cue. The generalizability to a real life situation would, how-
ever, be limited.
The process approach. The process approach involves remediation of deficits

in specific cognitive areas (e.g., memory). These areas are related to specific
Rehabilitation of Emotional Deficits 415
brain systems and can be analyzed into component parts. With regard to emo-
tional processing, remediation could be conducted whether the problem occurred
in a specific processing mode (e.g., perception), communication channel (e.g.,
facial), emotional dimension (e.g., pleasantness), or discrete emotion (e.g., hap-
piness).
The process approach proceeds through one or more of these areas in a pro-
gression from less difficult to more difficult tasks. Many of these techniques are
derived from the cognitive (e.g., Anderson, 1996), experimental (e.g., Raichle et
al., 1994), and rehabilitation psychology (e.g., Wilson et al., 1994) literature. In-
dividualized training programs are generally based on the specific patient's pat-
tern of cognitive and communicative impairment and are oriented toward their
vocational goals and ability to live independently. Within the process approach,
three general methods have been utilized. The first, retraining, involves im-
provement or restoration of specific cognitive functions. The second involves
training in the use of specific compensatory strategies that help the person adapt
to his or her limitations. The third involves increasing the individual's awareness
by training the capacity to regulate one's behavior. Each of these methods might
be applied to emotional deficits.
Retraining was conceptualized by Luria (1963) as facilitating recovery of cog-
nitive functions after brain injury through newly established connections within
the central nervous system. Luria (1963) speculated that the underlying mecha-
nism of recovery involves reorganization within the damaged brain region, as
well as transfer of function to the opposite cerebral hemisphere. When one neural
system breaks down, a second system may become operational and take over for
the damaged system (Stein, Brailowsky, & Will, 1995).
Several approaches in speech-language pathology utilize the idea of trans-
fer of function to the opposite side of the brain. For example, Melodic Intona-
tion Therapy (Helm-Estabrooks, Nicholas, & Morgan, 1989) exploits right-
hemisphere prosodic abilities to promote language use in patients with damage
to language centers in the left hemisphere. Perhaps the opposite could be done
for individuals with aprosodia (Ross, 1997).
Compensation training, on the other hand, is based on the idea that some
processes cannot be regained following brain damage. Rather, the individual is
shown how to work around the lost function. Examples include using a differ-
ent sensory modality (e.g., tactile input for visuospatial deficits [Luria, 1963]) or
employing an external aid (e.g., a notebook for memory loss [Sohlberg & Ma-
teer, 1989]) or an alternative communication system, such as a computerized lap-
board to help patients discuss family issues or state how they feel (Silverman,
1995). Persons with flat facial affect could, for example, be taught to exagger-
ate prosody.
The noetic approach focuses on increasing awareness of deficits and on the
capacity to recognize and regulate behavior. This approach has been used pri-
marily in individuals with frontal-system pathology. The individual learns

through practice to internalize specific skills or behaviors and to apply them to
a variety of situations (e.g., Cicerone & Wood, 1987; Sohlberg, Sprunk, & Met-
zelaar, 1988). Related to the noetic approach are metalinguistic forms of
speech-language therapy (e.g., Myers, 1994).
Multidisciplinary treatment
Although it is essential that treatment be individualized, many programs have
stressed the benefits of the milieu approach (Ben-Yishay et al., 1985). Depend-
ing on the nature of the deficits, this approach can include a neuropsycholo-
gist, speech-language pathologist, psychotherapist, social worker, vocational
counselor, physiatrist, psychiatrist, occupational therapist, physical therapist,
and/or recreational therapist. See Table 16.1 for a brief description of the typi-
cal functions of each member of the rehabilitation team.
In many settings, each professional operates independently, and the patient is
scheduled for separate appointments with several services. In other settings, the
team meets regularly to discuss each case but appointments remain separate. In
milieu settings, issues are dealt with daily in as natural an environment as pos-
sible. In addition to individual sessions, there are frequent group sessions and
community-based activities.
Caregiver participation
The patient's significant other is considered a critical member of the rehabil-
itation process. Most caregiver programs focus on education about the nature of
the problem and its psychological, communicative, and neurological conse-
quences. The second avenue focuses on altering the patient's environment and
examining communication roles between partners. For example, Lubinski (1981)
noted that certain environments may contain removable obstacles to communi-
cation (e.g., noise elimination). Lyons (1992) underscored the importance of
working directly with a patient's significant others. People in the patient's envi-
ronment are taught to establish and practice alternative modes of functioning and
to accept patients' limitations.
Assessment Techniques for Rehabilitation
The evaluation of individuals who participate in rehabilitation requires some vari-

ation from the usual neuropsychological assessment techniques. An additional
goal of this assessment is to determine the relative contributions of the individ-
ual's neurological disorder and his or her reaction to it. Diagnostic accuracy is
extremely important so that treatment can be appropriately tailored. For exam-
ple, in the case of depression, it is critical that standard self-report scales of de-
pression not be the only measures employed. Standard scales typically contain
Table 16.1 Role of Rehabilitation Professionals

TITLE DEGREE CLINICAL FUNCTION
Neuropsychologist Ph.D. Perform cognitive, personality, and mood

assessment
May do rehabilitation
Speech Language M.A. Provide speech and language assessment
Pathologist CCC-SLP and treatment
Provide swallowing assessment and treatment
May do rehabilitation
Psychotherapist Ph.D. Perform psychotherapy
or M.A. May do personality and mood assessment
May do relaxation training
Social Worker M.S.W. Provide discharge planning
Mediate family meetings
May do psychotherapy
Vocational M.A. Perform vocational assessment
Counselor Provide vocational counseling
Physiatrist M.D. Perform physical examination
Provide rehabilitation planning
Prescribe medication (including pain relief)
Psychiatrist M.D. Perform personality and mood assessment
Prescribe psychotropic medication
Occupational M.A. Evaluate hand functions
Therapist O.T.R. Provide splints, braces
Evaluate cognitive skills required for daily living
Rehabilitate activities of daily living
Physical Therapist M.A. Evaluate motor functions
R.P.T. Provide braces, cane
Rehabilitate motor functions
Provide pain management
Recreational M.A. Evaluate recreational interests
Therapist or B.A. Train compensations needed to participate in
recreational activities
vegetative items (e.g., lack of energy and trouble initiating activities) that could
easily be due to neurological dysfunction rather than to depression per se. Test-
ing of language, including pragmatics, should be augmented with informal ob-
servations of communication abilities in naturally occurring situations. It is crit-
ical that the speech-language examination also evaluate resonance, phonation,
prosody, and respiration, as these processes may interfere with affective expres-
sion. Because it is likely that individuals will be tested both before and after treat-
ment, objective and reliable clinical measures should be utilized. Finally, it is es-
sential that measures of generalization be employed from the time of initial
assessment. Measures of generalization should include those that are specific to
processes being rehabilitated and those that assess everyday functioning.
Generalization of Treatment
The importance of generalizing treatment to daily life is ingrained in clinical

practice (Raskin & Gordon, 1992). An understanding of generalization and how
to facilitate it, however, are still, for the most part, lacking in the field of reha-
bilitation. Generalization of cognitive rehabilitation, for example, has been de-
scribed by Gordon (1987) at three levels: (7) gains from remediation are observed
on the same materials on separate occasions, (2) improvement on training tasks
is also observed on similar but not identical sets of tasks, and (3) functions gained
in training transfer to functions in day-to-day living.
Recently, Sohlberg and Raskin (1996) proposed generalization strategies
(adapted from Anderson, 1996; Stokes & Baer, 1977) that could be broadly im-
plemented in both research and clinical practice in emotional rehabilitation. These
principles include actively planning for and programming generalization from
the beginning of the treatment process, identifying reinforcements in the natural
environment, programming stimuli common to training and real-world environ-
ments, and using sufficient examples when conducting treatment.
The most difficult of these principles is the selection of measures of general-
ization. Three approaches have been suggested (Sohlberg & Raskin, 1996). The
first applies to the treatment targeted and might include a rating form targeting
behaviors specifically trained, such as a questionnaire to be completed by a sig-
nificant other regarding the patient's ability to verbally express sadness. The sec-
ond includes measures of everyday functioning specific to the area of treatment,
such as emotional expression. The final approach applies to the individual's daily
life in more general terms. Measures of generalization should examine social in-
teraction, productive activities, and independence. Examples of such measures
include the Community Integration Questionnaire (Wilier & Corrigan, 1994) and
the Craig Handicap Assessment and Reporting Technique (Whiteneck et al.,
1992).
Finally, generalization may be enhanced by having a spouse or significant other
administer practice exercises that teach the patient to use compensatory strate-
gies. Generalization may also be enhanced by having the patient practice using
the system in a natural environment (e.g., school, workplace, or home).
TREATMENT OF EMOTION
The emotional deficits that follow neurological disorders and acquired brain in-
jury have typically been treated with medication, cognitive therapy, and behav-
ior therapy. Recent work suggests that affective difficulties are amenable to di-
rect remediation techniques (Myers, 1998; Tompkins, 1995). For example,
Hornak, Rolls, and Wade (1996) suggest that individuals who have deficits in
the prosodic expression of emotion could be encouraged to take advantage of in-

tact facial emotional expressions when talking to others (i.e., a compensation
technique). In a similar vein, Borod, Bloom, and Haywood (1998) recommend
that patients with right-brain damage who demonstrate deficits in the verbal ex-
pression of emotion be systematically exposed to a hierarchy of situations that
gradually increase in emotional intensity.
Certain neurological etiologies have yielded predictable patterns of emotional
disorders. For example, patients with left-brain damage and aphasia have shown
relatively preserved emotional expression (Blonder et al., 1993) or have demon-
strated increased emotional intensity while producing affective expressions (Kent
et al., 1988; Montreys & Borod, 1998). In contrast, patients with right-brain dam-
age have demonstrated reduced accuracy and intensity in producing emotional
expression (Borod, 1993a). Cognitive and communication abilities can interact
with emotional deficits and thereby influence treatment approaches. For exam-
ple, auditory or attention deficits can impair the interpretation of emotional
prosody or facial expression, and limitations in speech movement can reduce the
production of verbal emotional expression.
Emotional Deficits Associated with Common Neurological Disorders
Traumatic brain injury

Traumatic brain injury produces a wide range of emotional changes, depend-
ing on the mechanism of injury and premorbid factors. Because of the suscepti-
bility of the prefrontal cortex to damage in acceleration/deceleration injuries,
common emotional changes with such injuries include apathy, impulsivity, poor
emotional control, and poor social judgement. Individuals frequently experience
depression, anxiety, and post-traumatic stress disorder. Depending on the conse-
quences of the injury on daily living, individuals can experience a "shaken sense
of self (Kay, 1992) in which poor cognitive performance leads to poor social
or occupational functioning, which in turn leads to lowered self-esteem, increased
depression, and increased anxiety. Rehabilitation efforts must include attempts
to interrupt this cycle and deal with the interacting cognitive and emotional symp-
toms together.
Stroke
Stroke has been the focus of cognitive rehabilitation, speech-language ther-
apy, and a large number of studies aimed at treating depression. There is some
controversy regarding lesion location and incidence of depression (Starkstein &
Robinson, 1992). Treatment in the acute phase post-stroke must be different than
that after more recovery has occurred. There is some evidence that depression
following stroke becomes worse over time (Robinson & Price, 1982). In addi-
tion to depression, survivors of stroke may experience apathy and indifference

(see Robinson & Manes, Chapter 10, this volume).
Parkinson's disease
Depression is the emotional disorder most frequently associated with Parkin-
son's disease (PD) (Cummings, 1986). The depression does not appear to be
merely a reaction to the cognitive and motoric deficits because the symptoms do
not covary (e.g., Mayeux et al., 1984). As would follow, treatment of the motor
symptoms alone does not generally improve the depression. As in other neuro-
logical disorders, the diagnosis of depression must be made without reference to
the masked face, reduced motor activity, speech disorder (i.e., dysarthria), and
slow information processing commonly seen in PD. As PD is a progressive dis-
order, treatment of cognition and communication must be aimed at slowing pro-
gression rather than at amelioration. In addition to depression, a number of stud-
ies have shown deficits in PD patients relative to neurologically healthy normal
adults for the perception and expression of facial and prosodic emotion (e.g.,
Borod et al., 1990; Brozgold et al., 1998; Buck & Duffy, 1980; Scott, Caird, &
Williams, 1984).
Alzheimer's disease
Personality and psychiatric disturbances in senile dementia of the Alzheimer's

type (SDAT) vary greatly according to premorbid personality and stage of the
disease. The disease can lead to a wide range of behavioral and emotional diffi-
culties and are often the earliest symptoms. Apathy is common, as are agitation
and rage (Haley, Brown, & Levine, 1987). There is evidence of an increased in-
cidence of depression, but this decreases as the disease progresses. Approximately
30% of SDAT patients meet criteria for clinical depression (Borod, 1996).
SDAT is a progressive disorder and thus must be treated with goals that are
similar to those in PD. These include, for example, putting systems in place in
anticipation of later deterioration. Frequently, these systems involve environ-
mental modification. Behavioral symptoms appear to change somewhat pre-
dictably as the disease progresses. In early stages, individuals have mood swings
and increased dependence. This is often followed by apathy, agitation, and/or
restlessness; increased violence or anger; and frequent suspiciousness.
Multiple sclerosis
Multiple sclerosis is a demyelinating disease of the central nervous system that

results in lesions of the myelin sheath. These lesions begin with inflammation
and edema and later become plaque formations (Adams, 1993). In some indi-
viduals, the disorder is progressive, while in others there may be remission, pos-
sibly due to remyelination (Poser et al., 1983). There may also be diffuse effects,
including cerebral atrophy (Adams, 1993). The most common symptoms are fa-
tigue, motor weakness, motor incoordination, spasticity, visual disturbance,

paresthesia, and pain (Rao, 1986). Emotional symptoms are likely to include de-
pression or euphoria (Minden & Schiffer, 1990; Rao, Huber, & Bornstein, 1992).
Because symptoms may be slowly progressive or fluctuating, many patients
may be referred first to psychiatrists to rule out conversion disorder, which
would impact on emotional symptoms and adjustment. Of note, the clinical
course of multiple sclerosis is highly variable (Rao, 1986). If an individual is
on a progressively deteriorating course, standard retraining techniques may be
inappropriate. Rather, a focus on compensatory strategies and environmental
modifications that are trained early on can be useful throughout many stages
of the illness.
Treatment of Specific Emotional Deficits
This section focuses on particular emotional symptoms that may occur with a
range of neurological disorders. Although treatment will vary depending on di-
agnosis, the basic approach to these symptoms is likely to be similar. Many of
these approaches are borrowed from standard psychotherapy practice but are
modified for use with individuals with neurological dysfunction. In all cases, the
approach chosen will depend on the cognitive profile of the individual, as well
as on the emotional symptom(s). Hibbard and colleagues (1990a), for example,
argue that more cognitively impaired individuals respond better to behavioral ap-
proaches, whereas those with greater insight and cognitive functioning respond
better to cognitive therapy approaches.
The psychopharmacological treatment of emotional disorders in persons with
brain damage requires special consideration. For many individuals, treatment with
medication may be contraindicated due to coexisting medical problems. In ad-
dition, the side effects of psychopharmacological agents may further interfere
with cognitive and emotional functioning. For the clinical management of the
patient, it is important to be aware of his or her medication status and to discuss
with the prescribing physician the effects of these medications on functioning.
For example, when treating depression, anticholinergic use (such as tertiary amine
tricyclics) should be closely monitored for increased confusional state, slurred
speech, blurred vision, and fatigue. Fluoxetine can cause sleep changes and
headache, as well as increase seizure risk. All non-monoamine oxidase inhibitor
antidepressants can cause sedation. Treatment of anger includes the use of sero-
tonergic drugs, antiseizure medication, and benzodiazepines, which can cause fa-
tigue and sedation. Another drawback to pharmacological management is that
many people are already heavily medicated for coexisting conditions. Finally,
not all individuals respond well to or are compliant with taking medication. For
further discussion of pharmacological intervention, see Lisanby and Sackeim
(Chapter 18, this volume).
Depression
Depression is a very frequent concomitant of acquired neurological dysfunc-
tion. For post-stroke depression, Hibbard and colleagues (e.g., Grober et al., 1993;
Hibbard et al., 1990a,b) suggest that psychotherapy may be the treatment of
choice. Psychotherapy allows persons with neurological dysfunction to learn new
coping styles, improve social skills, and increase their sense of mastery and con-
trol, which can help prevent the recurrence of depression.
Cognitive therapy. Using the cognitive therapy model (Beck et al., 1979), Hib-
bard and colleagues (1990a) provide a series of principles specific to treatment
of post-stroke depression that can be adapted for persons with other types of neu-
rological dysfunction. These principles include the following: (7) level of cog-
nitive functioning moderates treatment strategies used; (2) cognitive remediation
enhances patients' ability to profit from therapy; (3) new learning and general-
ization are difficult for stroke patients; (4) patients' awareness of depressive
symptomatology moderates the therapeutic strategy; (5) mourning is an impor-
tant component of treatment; (6) premorbid personality, lifestyle, and interests
provide a context for understanding current behavior; (7) understanding the dis-
crepancy between actual and perceived losses is essential to treatment; (8) rein-
forcing even small therapeutic gains improves mood; (9) emphasis on the col-
laborative therapeutic relationship facilitates a working alliance; (10) to ensure
continuity of treatment, session flexibility is essential; (11) fluctuations in med-
ical status affect the course of treatment; (12) distortions of family members must
be addressed in therapy; (13) family members' mourning must be addressed; and
(14) family members are important therapeutic helpers. In conjunction with tra-
ditional cognitive therapy, these principles provide specific tools with which to
address the depression following neurological impairment.
The cognitive therapeutic approach assumes that depression is caused by "dys-
functional thoughts" (Beck et al., 1979). Cognitive therapy focuses on identify-
ing aspects of these thoughts that are irrational and challenging the distortions
with more rational thinking. Importantly, cognitive therapy is an active, direc-
tive, and time-limited approach. In this approach, maladaptive assumptions de-
veloped from prior experience are identified (e.g., "If I don't do everything per-
fectly, then I'm a failure"). The therapy includes monitoring these negative
thoughts; learning to recognize the connections among thoughts, feelings, and
behavior; examining evidence for and against the distorted thoughts; substitut-
ing more realistic interpretations; and altering dysfunctional beliefs that can dis-
tort an individual's experiences.
Behavioral interventions. As in traditional cognitive therapy, behavioral strate-

gies are also an important component of treating depression. It may be the pri-
mary approach for persons with severe cognitive deficits and/or limited aware-
ness (Grober et al., 1993). Behavioral interventions may be incorporated into the
therapeutic process. Role-playing coping responses can be used to enhance gen-
eralization, and assertiveness training can help patients regain a sense of com-
petence.
Behavioral assignments, based on work explored in a session, are provided to
test and challenge dysfunctional thinking. For example, if a person's belief is
that "because I have a brain injury, I can't do anything well," then tasks that eas-
ily can be accomplished should be employed. Furthermore, assignments should
target symptoms of depression (e.g., loneliness) and involve activities that were
previously pleasurable (Stein & Raskin, 2000). As the person progresses, a feel-
ings log or diary (Beck et al., 1979) is sometimes useful.
The grieving process. Recovering from depression after brain damage is analo-
gous to the grieving process (Kubler-Ross, 1969) because it identifies losses that
are not always obvious to the patient. Such losses include cognitive abilities,
emotional control, work status, self-esteem, autonomy, sense of self, intimacy,
pain-free health, control over how one spends time (e.g., going to appointments
and contacting insurance companies), and plans for the future.
Anxiety and post-traumatic stress disorder

Anxiety occurs in a wide range of neurological conditions as a physiological
result of injury and as a reaction to decreased cognitive resources.
Cognitive and behavioral strategies. Immediately following an injury or illness,

daily functioning is often disrupted. Common tasks may be challenging or fa-
tiguing, and the individual's confidence may become eroded. Often, the most
common symptom reported by the patient is anxiety. Providing the patient with
information about anxiety, along with reassurance of its reversible nature, may
lead to increased insight. Behavioral strategies for anxiety management might in-
clude controlled/deep breathing; progressive muscle relaxation; frequent/brief
walks or stretching when symptoms begin to manifest; and improved sleep pat-
terns and overall amount of sleep.
Relaxation training. Relaxation training may be a useful method for reducing

anxiety that occurs subsequent to neurological disorder. A connection is estab-
lished between the abilities to enter a relaxed state under ideal circumstances and
to generalize relaxation to other situations. Relaxation training may take the form
of therapist-guided exercises in sessions or listening to similar exercises on com-
mercially produced cassettes.
Systematic desensitization. Systematic desensitization is a behavioral approach

that entails relaxation in conjunction with gradual exposure to trauma-related
stimuli. In this way, individuals improve control over their reactions to these
stimuli within treatment, which can then be generalized to daily life. One ap-
proach to systematic desensitization requires that descriptions of images, activi-
ties, or situations that elicit symptoms be recorded. These scenarios can be ranked
or rated by degree of anxiety. While the patient is in a relaxed state, the thera-
pist begins describing the triggers that produce anxiety. If the individual indi-
cates symptoms of anxiety, the therapist ceases or decreases exposure to the trig-
ger and facilitates relaxation. Persons with cognitive dysfunction may require a
more structured approach toward anxiety reduction (e.g., written instructions and
schedules) (Hovland & Raskin, 2000).
Anger
Increases in irritability and expressions of anger or frustration are frequently
reported with many neurological conditions. Anger and frustration may be ex-
pressed as negative self-talk, verbal abusiveness, and/or physical aggressiveness.
Stress and turmoil are created in the home, and significant problems at work may
occur when individuals exhibit such behaviors. Disinhibition, common in brain
damage, may result in impulsivity, distractibility, fatigue, and irritability. Pre-
morbid personality and reactive emotional responses may also contribute to the
expression of anger.
McKay, Rogers, and McKay (1989) suggest that anger can reduce stress by
discharging or blocking awareness of painful levels of emotional or physical
arousal. Anger may serve to dissipate painful affect, reduce or eliminate painful
sensations, release tension, and be a response to perceived threats.
Cognitive therapy. Hovland and Mateer (2000) provide a comprehensive dis-

cussion of the treatment of anger after brain injury. The following treatment ap-
proaches are based largely on their work.
Early in treatment, if concerns arise regarding the potential for escalating ag-
gression or violence, steps should be taken to make the environment safe via en-
vironmental management. This might include having potential weapons removed,
removing alcohol or drugs, providing supervision, or contacting appropriate agen-
cies. The family or significant others can be advised of environmental strategies,
such as leaving the person when signs of anger develop or distracting the per-
son by changing the focus of conversation or activity.
Behavioral therapies. Another approach to anger management has a more be-

havioral focus. The behavioral approach tends to be concrete, focuses on mea-
surable behaviors, and is data based and hierarchical in nature. This systematic
approach is of particular benefit for individuals whose irritability and anger may
have a more organic than situational basis and who have difficulty with ab-
straction, memory, attention, or self-awareness.
Novaco (1979) described the stress inoculation approach to anger control as

not attempting to suppress anger but rather to minimize maladaptive affects and
maximize adaptive functioning. Novaco (1979) specified the following stages for
this training: preparation for provocation, confrontation, coping with arousal, sub-
sequent reflection, conflict unresolved, and conflict resolved. Wood (1984, 1987)
described a large number of cases in which behavior therapy was used to man-
age behavioral disorders in brain-injured patients (including aggression). Only a
few studies have documented the efficacy of behavioral intervention for anger
control in brain-injured individuals (e.g., Lira, Carne, & Masri, 1983; McGlynn,
1990; Uomoto & Brockaway, 1992).
It is particularly helpful for the neuropsychologist, speech-language patholo-
gist, and cognitive therapist to work in tandem to establish the connection be-
tween frustration and cognitive deficits. Under conditions of greater cognitive
demand, frustration is likely to escalate. For example, the cognitive therapist may
be addressing problems with distractibility, which could be tied to the patient's
irritability. Problems with divided and alternating attention on tasks can adversely
affect emotional homeostasis. Finally, it is important to provide information about
the relationship between emotional and cognitive deficits to the client's signifi-
cant other, family, friends, coworkers, and/or employer.
Much of the focus in treatment itself is on identifying what has been termed
the angry behavior cycle (Goldstein et al., 1987). Sessions focus on recognizing
anger cues, using relaxation techniques, and using self-evaluation and reward.
Anger-provoking situations are role-played with the therapist, and information
is gathered about behavior outside of sessions through completion of anger-
management records.
Apathy and indifference
Apathy is described by Stuss and colleagues (Chapter 14, this volume) as an

absence of responsiveness that is demonstrated by poor self-initiation of action.
Apathy can be observed in overt behavior but also in more subtle ways. For ex-
ample, during memory testing, the individual with neurological dysfunction may
not provide a response in a recall paradigm but then may produce considerable
information when prompted. There also may be a poverty of language when asked
to provide biographical information or to describe pictorial stimuli in the absence
of aphasia. In severe cases, apathy associated with depression can mimic de-
mentia. In younger individuals, apathy is often mistaken for being lazy, malin-
gering, or having a psychiatric disturbance (Lezak, 1995).
Stuss and colleagues (Chapter 14, this volume) suggest that apathy can be dif-
ferentiated by symptomatology and underlying brain structure. For example, dam-
age to any one of five frontal/subcortical circuits leads to a unique form of apathy.
Campbell and Duffy (1997) point out the importance of evaluating environ-
mental and family contributions to apathy. Family therapy is recommended us-
ing a problem-centered model that includes education, clarification of roles, in-

struction in interpersonal communication, and techniques for problem-solving.
Rehabilitation approaches to apathy have included behavioral techniques. The
individual can be given structured activities to perform at preset times so that it
is not up to him or her to initiate activities. Opportunities for reward are pro-
vided. At the same time, the individual can be educated about the neurological
cause of apathy. Increased awareness is then made a treatment goal. With this
type of treatment, videotapes of the individual interacting in group settings or
feedback from peer group members can be very helpful (Sohlberg et al., 1993).
Behavior modification of apathy was used successfully by Rosenthal and
Meyer (1971) in a case study of a woman diagnosed with clinical abulia due to
non-neurological causes. She was helped to set goals, use new problem-solving
techniques, and increase environmental opportunities for reward.
Affective Deficits
Affect is expressed through the complex combination of verbal language, voice,

prosody, face, gesture, and posture. When affective communication is impaired,
there may be marked difficulty in the discrimination and/or production of a range
of facial expressions. In addition, deficits in the perception and use of prosody,
gesture, body posture, and body position may diminish an individual's partici-
pation in communication. Such patients may demonstrate difficulty in interpret-
ing situational cues that signal emotional meaning.
Affective disorders occur in a variety of neurological conditions, including
stroke, PD, traumatic brain injury, and SDAT. For example, patients with stroke
and damage to the right cerebral hemisphere have demonstrated deficits within
the facial (Borod, 1992), prosodic (Tompkins, 1995), and verbal (Borod, Bloom,
& Haywood, 1998) channels of emotional communication. PD patients have re-
duced facial expression and articulatory deficits that limit their expression. Pa-
tients with traumatic brain injury, right-brain damage, and SDAT often demon-
strate pragmatic communication disorders and deficits in discourse (Ferrand &
Bloom, 1997).
Several traditional approaches from speech-language pathology may be em-
ployed to treat affective communication disorders. Augmentative and Alterna-
tive Communication (AAC) systems may be adapted to give patients access to
the expression of a wide range of emotional responses (Silverman, 1995). Aug-
mentative and Alternative Communication systems can take the form of lap-
boards, notebooks, or electronic devices that use synthesized speech. Prosodic
deficits may be addressed with a variety of behavioral methods, for example, res-
piratory monitoring through visual feedback. Pragmatic language intervention
may raise a patient's awareness of interpersonal communication cues (e.g., turn-
taking or topic selection). Communication groups can provide an opportunity to
practice communication strategies in new situations. Interpersonal communica-

tion approaches to remediation have been suggested by Davis and Wilcox (1985).
CONCLUSIONS
In summary, a number of approaches to rehabilitation have been applied to emo-

tional processing deficits. These include cognitive remediation, behavior modi-
fication, speech-language therapy, and environmental management (e.g., care-
giver participation and milieu approaches to treatment), as well as psychotherapy
and psychopharmacology.
The treatment of emotional deficits needs to be applied concurrently with ther-
apy for speech and language because auditory comprehension and expressive
communication (i.e., verbal and nonverbal) seem to constrain emotional pro-
cessing. For example, in stroke, a person with a left-hemisphere lesion and re-
duced receptive and expressive language would be a poor candidate for an af-
fective treatment approach that relied on verbal mediation.
From a theoretical perspective, the approach taken here may have some appli-
cation to the model of emotional processing proposed by Borod (Borod, 1993b;
Borod et al., in press). Specifically, Borod (1993b) described a componential ap-
proach that addresses the issue of separate and related systems organized with re-
spect to four different hierarchical levels of emotion: processing mode (i.e., ap-
praisal, perception, arousal, experience, expression, and behavior); communication
channel (i.e., facial, prosodic, lexical, gestural, and postural); emotional dimen-
sion (e.g., pleasant/unpleasant, aroused/nonaroused, and approach/avoidance); and
discrete emotion (e.g., happiness, disgust, anger, and surprise). Within each level,
there is the opportunity for interaction among individual elements or components.
We believe that processing modes are useful in cognitive rehabilitation (e.g.,
perception treated by cognitive remediation); communication channels are
amenable to intervention by speech-language therapies (e.g., prosodic expres-
sion of emotion treated by visual feedback about respiration); emotional dimen-
sions might be treated by pharmacological agents (e.g., a mood disorder treated
by antidepressants); and discrete emotions may be best addressed by behavioral
approaches (e.g., stress disorders treated by psychotherapy). The componential
model is ripe for further testing and provides a promising approach for research
in the treatment of emotional deficits from a neuropsychological perspective.
ACKNOWLEDGMENTS
This project was supported, in part, by a Trinity College Faculty Research Expense Grant to S.A.R.,
by a Hofstra University Research and Development Award to R.L.B., and by NIMH grant MH42172
to J.C.B.
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17
Emotional Processing in Schizophrenia:
A Focus on Affective States
CHRISTIAN G. KOHLER, RUBEN C. GUR,

AND RAQUEL E. GUR
Schizophrenia has traditionally been viewed as a psychiatric illness with promi-

nent clinical features of psychosis and cognitive dysfunction. Psychotic symp-
toms frequently consist of auditory hallucinations, paranoid or somatic delusions,
and ideas of reference. Contrary to negative symptoms and cognitive dysfunc-
tion, psychotic—or "positive"—symptoms commonly fluctuate with the course
of illness and respond to neuroleptic treatment.
Deficits in cognition, considered a stable hallmark of schizophrenia, have long
been described, and in the early part of the twentieth century were used to dif-
ferentiate schizophrenia from affective illnesses. Recent investigations have
shown quite marked neuropsychological functioning deficits in schizophrenia, of
a magnitude similar to performance of patients with brain injury (for review, see
Heaton & Crowley, 1981). Neuropsychological impairment has been found in
patients treated with medications (Braff et al., 1991), as well as in untreated pa-
tients with first-episode schizophrenia (Censits et al., 1997; Saykin et al., 1994).
Neurocognitive deficits have been most consistently noted in abstraction and
mental flexibility (Goldberg et al., 1989), attention-vigilance (Censits et al., 1997;
Nuechterlein & Dawson, 1984; Saykin et al., 1994), and verbal memory and
learning (Braff et al., 1991; Goldberg et al., 1989; Kareken et al., 1995; Saykin
et al., 1991, 1994). While not as pervasive or severe, neuropsychological im-
pairment has also been described in affective disorders, specifically depression.
432
Affective States in Schizophrenia 433
Such disorders have generally been evaluated in middle-aged or elderly patients.

Impairments have been reported in verbal memory and learning (Breslow, Koc-
sis, & Belkin, 1980; Brown et al, 1994; Stromgren, 1977; Weingartner, Gold,
& Ballenger, 1981) and in attention (Brown et al., 1994; Caine, 1981; Cummings
& Benson, 1984; Frith, Stevens, & Johnstone, 1983; King & Caine, 1990). Some
investigators have found cognitive dysfunction to improve with treatment of de-
pressed mood (Frith, Stevens, & Johnstone, 1983; Malone & Helmsley, 1977;
McAllister & Price, 1982). This supports the initial terminology of "pseudode-
mentia" (Kiloh, 1961), which distinguished reversible cognitive dysfunction in
the setting of depression from progressive dementias. Others have, however, sug-
gested cognitive dysfunction to be independent of mood changes (Gold, Wein-
gartner, & Ballenger, 1979; Henry, Weingartner, & Murphy, 1973; Reuss, Sil-
berman, & Post, 1979; Weingartner, Gold, & Ballenger, 1981).
Early descriptions of the phenomenology of schizophrenia included affective
disturbance in emotional processing, such as abnormal expression and abnormal
experience, as symptoms inherent to, but not always characteristic of, the illness.
Kraepelin's binary model (1896) proposed an exclusivity of schizophrenia and
affective phenomena and delineated a clear distinction between dementia prae-
cox and manic depressive illness. By 1919, however, Kraepelin reported affec-
tive disturbances that were present at the onset of dementia praecox, "usually
anxious, despondent, they weep and lament, would like to die," and became less
prominent during later stages of the illness with more prominent somatic preoc-
cupation and self-neglect.
Eugen Bleuler (1911), whose views have been influential in our understand-
ing of schizophrenia, divided the phenomenology of schizophrenia into primary
and secondary symptoms. Primary symptoms—disturbances in affect, associa-
tion, ambivalence, and autism-were seen as partial, but necessary for the diag-
nosis. Secondary symptoms, which included not only delusions and hallucina-
tions but also depressed mood, could be absent or could change without any
alteration in the underlying process. He suggested that affective disturbances
could be either part of the underlying disease process or alternatively psycho-
logical reactions to the illness. By midcentury, Kurt Schneider (1959) described
first rank symptoms—hallucinations, delusions, thought broadcasting, and
control—to be characteristic of the illness. In this model, which greatly influ-
enced the conceptualization of schizophrenia in the United States and Europe,
affective disturbances were viewed as secondary symptoms.
Within the past decade and with attempts to further characterize symptoms of
schizophrenia, the concept of positive and negative symptoms was created (An-
dreasen & Olsen, 1982). Positive symptoms, which are often episodic in nature,
consist of hallucinations, delusions, bizarre behavior, and thought disorder. Al-
though positive symptoms are more easily identifiable and dramatic in nature, it
is the negative symptoms that have been described as characteristic of schizo-
phrenia since Bleuler's conceptualization of core symptoms. Negative symptoms

are typically present with the first onset of illness (Fennig et al., 1996), tend to
be chronic in nature, and may herald poorer outcome (Andreasen & Olsen, 1982).
They are characterized by affective flattening, alogia, avolition, anhedonia, and
inattention and are more pronounced in schizophrenia patients, particularly men,
than in patients with other psychotic disorders (Husted, Beiser, & lacono, 1995;
Reddy, Mukherjee, & Schnur, 1992; Shtasel et al., 1992). Negative symptoms
are thought to increase with duration of illness and may be worsened by neu-
roleptic medication with strong postsynaptic dopaminergic D2 blockade, such as
haloperidol, fluphenazine, and risperidone.
In this chapter, we examine current evidence for neural substrates of emotional
dysfunction in schizophrenia in the domains of expression, experience, and
recognition of emotion. Abnormal expression of emotional states usually con-
sists of flattening of affect and inappropriate affect. Abnormal experience in-
cludes decreased intensity of emotional experience and mood states, ranging from
depression to mania. Abnormal recognition is described as impaired ability to
recognize facial expression of emotion. Clinically, it appears that all three are
implicated in but by no means unique to schizophrenia, as other chapters in this
volume describe emotional functioning in mood disorders (Davidson & Hen-
riques, Chapter 11; Robinson & Manes, Chapter 10), brain-damaged patients
(Borod et al., Chapter 4), and other neurological disorders (Heilman et al., Chap-
ter 15).
CLINICAL MANIFESTATIONS OF DISORDERED

EMOTIONS IN SCHIZOPHRENIA
Clinical Features
Expression
Diminished affect in the facial expression of emotion has been considered since
Bleuler (1911) to be a core symptom in schizophrenia. Impairment commonly
consists of flat or inappropriate affect and may precede the onset of psychosis
by many years (Walker et al., 1993). It can be worsened by administration of
neuroleptics with strong nigrostriatal dopaminergic blockade, which can produce
extrapyramidal symptoms including pseudoparkinsonism and akinetic depression
(Krakowski, Czobor, & Volavka, 1997; Rifkin, Quitkin, & Klein, 1975; Van Put-
ten & May, 1978). Compared with healthy subjects, patients with depression, and
patients with parkinsonism, schizophrenic patients have been described to ex-
press less emotions, with a propensity for negative rather than positive emotions
(Brozgold et al., 1998; Martin et al., 1990). Several studies have suggested an
independence between subjective ratings and facial display of emotions in schiz-

ophrenia (Berenbaum & Oltmann, 1992; Kring et al., 1993; Sison et al., 1996).
People with schizophrenia have, however, been noted to be unreliable reporters
of their emotional experiences (Jaeger et al., 1990), and affective flattening may
indicate muted emotional experience.
A major difficulty in evaluating deficits of emotional expression in schizo-
phrenia stems from the potential overlap of this, and other negative symptoms,
with depression. McGlashan (1982) addressed the similarity and possible coex-
istence of negative and depressive symptoms. He distinguished between affec-
tive poverty ("aphanisis") and postpsychotic depression. The first occurred in pa-
tients who had recovered from an acute psychotic episode and shielded
themselves from uncomfortable stimuli. Postpsychotic depression was charac-
terized by sad, hopeless mood, psychomotor retardation with apathy, and neuras-
thenic complaints and was present in approximately 25% of patients at remis-
sion of the acute psychotic episode.
Investigators who attempted to explore the potential link between depressive
symptoms and negative features of schizophrenia evaluated patients at different
stages of the illness, ranging from acute schizophrenia (Kitamura & Suga, 1991;
Ring et al., 1991) to acute exacerbation in chronic schizophrenia (Goldmann et
al., 1992) and chronic stable schizophrenia (Craig et al., 1985; Kibel, Laffont, &
Liddle, 1993; Kuck et al., 1992; Prosser et al., 1987), and included patient sam-
ples in which women were not represented or were grossly underrepresented
(Craig et al., 1985; Kibel, Laffont, & Liddle, 1993; Kuck et al., 1992; Prosser et
al., 1987). Although several studies found little or no association between de-
pressive and negative features (Goldmann et al., 1992; Kibel, Laffont, & Liddle,
1993; Kuck et al., 1992), other studies (Craig et al., 1985; Kulhara et al., 1989;
Prosser et al., 1987) found an association between negative and vegetative fea-
tures of depression. Vegetative symptoms of depression consist of somatic and
nonspecific behavioral disturbances, such as anergia, anhedonia, insomnia, and
lack of appetite, and can be found in many psychiatric disorders. Kitamura and
Suga (1991) reported an association between depressive ratings and negative rat-
ings, specifically for avolition-apathy and anhedonia-asociality, and Ring et al.
(1991) noted a correlation between negative and depressive symptoms, but only
in male and not female patients. No study found a link between negative symp-
toms and depressive cognitions, which are more specific to depression and con-
sist of sadness, anxiety, guilt, tension, and somatic concern. Because of the un-
derrepresentation of women sex-specific effects cannot be ruled out.
In an attempt to evaluate whether these features are clinically separable, we
examined the relationship between clinical ratings of characteristic symptoms of
schizophrenia—negative and positive symptoms (Andreasen & Olsen, 1982)—
and clinical ratings for depression in a large sample of schizophrenic patients.
Patients were grouped into a high and low depression group according to ratings
on the Hamilton Depression Rating Scale. Subjects with depression scored 18 or

above on the 21-item Hamilton Depression Rating Scale, which indicates the
presence of at least moderate severity of depressive symptoms (Baxter et al.,
1985; Bench et al., 1993). The high and low depression groups, which are de-
scribed in more detail below, did not differ in severity of negative symptoms.
The lack of association argues that in schizophrenia negative symptoms are dis-
tinct from depression.
In our patient sample, as in other studies of emotional expression, there is a
need for objective quantitative measures of affect expression. Even the more elab-
orate methods, however, that have detailed procedures for establishing reliabil-
ity and validity (Ekman & Friesen 1976) ultimately rely on subjective ratings.
Experience
Emotional intensity. Historically, schizophrenia was thought to involve a de-

creased range of emotional experience. This was inferred from an inability to
identify one's own emotional experience and an impairment in facial expressionzyxwvuts
of emotions, or what is referred to as flattening of affect. A recent study (Schnei-
der et al., 1995) has tested this hypothesis formally with a standardized mood in-
duction procedure including happy and sad faces. The procedure was applied to
40 schizophrenic subjects and to healthy controls matched for sex. Patients ex-
hibited impaired ability to respond to mood induction, particularly for happiness,
irrespective of medication status (23 were taking neuroleptics and 17 were not)
and sex. Performance on mood induction was positively correlated with halluci-
nations and negatively correlated with the negative symptom complex of anhe-
donia (Fig. 17.1).
Depression. After the introduction of antipsychotic medications in the treatment

of schizophrenia, clinical reports appeared that described a dramatic increase in the
incidence of depression and suicide (Beisser, 1961; Hussar, 1962). Apart from the
explanation that many previously untreated patients were too disorganized to ex-
perience sad mood or to act on it, these reports coincided with the deinstitutional-
ization of patients, who were being exposed to the stresses of greater personal free-
dom and gradual reintegration into the community with variable success (Farberow,
Shneidman, & Leonard, 1962). Experience with the antihypertensive agent reser-
pine, also used to treat schizophrenia and known to cause depression in some pa-
tients, led to the concern that depression might result from pharmacotherapy in
schizophrenia. This led to the introduction of the term pharmacogenic depres-
sion (Galdi, 1983; Helmchen & Hippius, 1967). Several subsequent studies, how-
ever, have at least partially refuted an association. Indeed, there are reports of
patients with schizophrenia who were treated with antipsychotic medications and
showed improvement in both psychotic and depressive symptoms (Johnson, 1981;
Figure 17.1. Specificity for discriminating and experiencing valence-specific emotions

in schizophrenic patients. The z-scores are based on results with normal controls.
(Reprinted with permission from Schneider et al., 1995.)
Knights & Hirsch, 1981; Koreen et al., 1993; McGlashan & Carpenter, 1976;
Roth, 1970). A further suggestion was that treatment with antipsychotic med-
ications may cause depressive symptoms due to extrapyramidal motor distur-
bances (Craig et al., 1985; Johnson, 1981; Rifkin, Quitkin, & Klein, 1975; Van
Putten & May, 1978). This was termed akinetic depression.
The identification and treatment of depression in schizophrenia is clinically
important because at least 10% of people with schizophrenia commit suicide
(Miles, 1977), and the majority of these were depressed in the months preced-
ing their deaths (Cohen et al., 1964; Planansky & Johnston, 1971; Roy, 1981).
Depression occurs most commonly during the onset of psychosis (Bowers & As-
trachan, 1967; House, Bostock, & Cooper, 1987; Johnson, 1981; Knights &
Hirsch, 1981; Koreen et al., 1993; Mayer-Gross et al., 1955; McGlashan & Car-
penter, 1976; Roth, 1970; Steinberg, Green, & Durrell, 1967; Stern, Pillsbury, &
Sonnenberg, 1972). Reduction of acute symptoms and clinical stabilization are
associated with decline of depressive symptoms (House, Bostock, & Cooper,
1987; Knights & Hirsch, 1981; Shanfield et al, 1970), which may reemerge dur-
ing each relapse (Johnson, 1981; Koreen et al., 1993; Shanfield et al., 1970). Mc-
Glashan and Carpenter (1976) estimated that postpsychotic depression occurs in
25% of all psychotic episodes, although others have suggested a somewhat lower
incidence. Depression is unusual with increasing chronicity of illness, perhaps
because its symptoms are gradually replaced by negative symptoms (House, Bo-
stock, & Cooper, 1987).
In an effort to separate the effects of depression from symptoms primarily at-
tributable to schizophrenia, we compared a group of schizophrenia subjects with
depression to a group without depression. Subjects with depression were scored
18 or above on the 21-item Hamilton Depression Rating Scale (Kohler et al.,
1998a). There were 63 patients (35 men, 28 women) in the high ( 18) depres-
sion group and 81 patients (52 men, 29 women) in the low (<18) depression
group. The groups were compared on demographic and clinical variables and on
eight neuropsychological domains (abstraction-flexibility, attention-vigilance,
verbal memory, spatial memory, language, spatial functions, sensory functions,
and fine manual motor skills). The two groups differed in age at onset of illness,
severity of delusions (Tables 17.1 and 17.2), and performance in a single neu-
ropsychological domain: attention (Figs. 17.2 and 17.3). The specific component
of impaired attention was vigilance, with the poorest performance by women
with higher depression scores. The presence of specific attentional impairment
associated with depressive symptoms in schizophrenia is consistent with the hy-
Table 17.1. Demographic and Clinical Characteristics of Schizophrenic Groups with

High and Low Depression Scores
HIGH DEPRESSION LOW DEPRESSION
GROUP (HAM-HI): GROUP (HAM-LO):
MEAN (±SD) RANGE MEAN (±SD) RANGE
Sex
Male 35 52
Female 28 29
Race
White 27 45
Black 36 35
Other 0 1
Age at evaluation (yr) 30.0 (7.9) 17.1-44.8 29.8 (6.8) 16.7-44.0
Duration (yr) 6.5 (6.0) 0-24 7.8 (6.7) 0-29
Age at onset (yr)* 24.1 (7.2) 11-41 22.0 (5.4) 13-36
Hospitalizations (n) 1.9 (2.8) 0-57 3.4 (7.5) 0-12
Education (yr) 12.7 (2.4) 8-20 12.7 (1.9) 8-17
*p < 0.05.
HAM, Hamilton Depression Rating Scale.
Table 17.2. Clinical and Behavioral Features of Schizophrenia Groups with High and
Low Depression Scores
HIGH DEPRESSION GROUP LOW DEPRESSION GROUP
(HAM-HI) MEAN ( ± SD) (HAM-LO) MEAN (±SD)
Schizophrenia 47 70
Schizophreniform d/o 16 11
Never medicated 28 26
Previously medicated 35 55
21-item HAM
Score* 22.6 (3.5) 11.6(4.2)
Range 18-31 1-17
SANS
Affect 2.5 (1.3) 2.3 (1.3)
Alogia 2.6 (1.4) 2.2 (1.5)
Avolition 2.6 (1.3) 2.5 (1.5)
Anhedonia 3.2 (1.0) 3.0 (1.4)
Attention 1.9 (1.4) 1.8 (1.5)
SAPS
Hallucinations 2.8 (1.4) 2.4 (1.5)
Delusions** 3.6 (1.0) 2.9 (1.2)
Bizarre behavior 1.6 (1.3) 1.4 (1.3)
Thought disorder 2.0 (1.3) 2.0 (1.5)
*P < 0.001.
**P = 0.007.
HAM, Hamilton Depression Rating Scale; SANS, The Scale for the Assessment of Negative Symp-
toms; SAPS, The Scale for the Assessment of Positive Symptoms.
pothesis of frontal lobe dysfunction in depression because these regions have

been implicated in attentional processes.
Mania. Unlike depression in schizophrenia, mania has been much less commonly
described. In 1911, Bleuler postulated that any affective symptoms may occur in
the setting of schizophrenia, provided that criteria for certain fundamental schizo-
phrenic symptoms were met: splitting of cognition from emotion and behavior, for-
mal thought disorder, flat or blunted affect, autism, and ambivalence.
Manic symptoms in the setting of schizophrenia may represent a schizomanic
state or warrant the diagnosis of schizoaffective disorder. Patients with schizo-
phrenia sometimes display manic symptoms (Tsuang & Loyd, 1988) and become
agitated, irritable, impulsive, and insomniac as part of an acute psychotic exac-
erbation or in response to hallucinations and delusions. Usually these symptoms
are temporary, and the behavioral picture lacks more typical manic symptoms
(e.g., pressured speech, grandiosity, and elated mood). Kasanin (1933) coined
the term "schizo-affective psychosis" to describe a group of patients with sud-
den onset in youth, prominent affective and schizophrenic symptoms, external
Figure 17.2. Neuropsychological profile of schizophrenia patients with high (N = 63)

and low (N = 81) depression scores. The z-scores are based on results with normal con-
trols. ABF, abstraction-flexibility; ATT, attention; VMEM, verbal memory; SMEM, spa-
tial memory; LAN, language abilities; SPA, spatial abilities; SEN, sensory abilities; MOT,
motor abilities.
stressor, and good premorbid adjustment. The initial description did not specify
the relationship between schizoaffective disorder and affective disorders or schiz-
ophrenia.
The existence of schizoaffective disorder as a separate clinical entity has re-
peatedly been questioned. Over the years, different definitions for schizoaffec-
tive disorder have been proposed. Attempts to identify it as a variant of schizo-
phrenia or an affective disorder based on clinical symptoms, genetics, and
prognosis have yielded equivocal results (Lapensee, 1992). Schizoaffective dis-
order has been removed from the schizophrenia category since the introduction
of the third edition of the Diagnostic and Statistical Manual of Mental Disor-
ders (DSM-IH). The diagnostic criteria were narrowed in the revised DSM-III
by establishing the necessity of longitudinal, isolated psychotic symptoms. This
is unchanged in DSM-TV. The primary difficulty in diagnosing schizoaffective
disorder is differentiation from schizophrenia with atypical affective disorder and
bipolar disorder or major depression with mood incongruent psychotic features.
In schizoaffective disorder, affective symptoms are a prominent, if temporary,
part of the illness. In contrast, in the affective illnesses, psychotic symptoms are
limited to acute exacerbations.
Figure 17.3. Attention subitems for male and female schizophrenia patients with high
(MALE_HI, FEMALE_HI) and low (MALE_LO, FEMALE_LO) depression scores on
subtests of attention. WRD, word condition; COL, color condition; CLWD, color word
condition; VIG, vigilance; DISTR, distractibility; DSP, digit span; DSY, digit symbol.
The z-scores are based on results with normal controls. Depressed and nondepressed schiz-
ophrenia patients differ in vigilance. (Reprinted with permission from Kohler et al., 1998a.)
Several hypothetical models have been formulated that attempt to place schiz-
ophrenic symptoms in the context of other psychiatric symptoms and make the
binary distinction between affective and schizophrenic disorders obsolete. The
"continuum model" (Crow, 1985) proposes purely affective and schizophrenic
disorders to be at opposite ends of a spectrum rather than mutually exclusive. In
the "hierarchical schema of symptoms" (Foulds & Bedford, 1975), disorders lo-
cated in a pyramidal hierarchy exhibit not only illness-specific symptoms but
also nonspecific symptoms of disorders located on lower, but not higher, pyra-
midal steps.
Recognition
Over the last 15 years a large body of literature has examined recognition of
emotion in brain-related disorders and healthy people as measured by the ability
to identify the emotional quality of facial expression. In healthy subjects, gen-
der-related effects were reported for emotion recognition (Erwin et al., 1992; Na-
tale, Gur, & Gur, 1983). Women showed better accuracy for brief exposures, and
men were less sensitive to expressed sadness in female faces. Impairment of emo-
tion recognition has been found in right-brain injuries (Adolphs et al., 1994;
Borod et al., 1993), schizophrenia (Cutting 1981; Feinberg et al., 1986; Heim-
berg et al., 1992; Schneider et al., 1995; Walker, McGuire, & Bettes, 1984), de-
pression (Feinberg et al., 1986; Gur et al., 1992), and Huntington's chorea (Ja-
cobs, Shuren, & Heilman, 1995).
In schizophrenia, investigators using emotion recognition tasks found that
schizophrenic patients performed more poorly than depressed patient groups and
controls (Feinberg et al., 1986; Gessler et al., 1989; Schneider et al., 1992; Walker,
McGuire, & Bettes, 1984; Zuroff & Colussy, 1986). In studies that included a
control task such as facial recognition or age discrimination, however, investi-
gators found impaired performance of schizophrenic patients on the control tasks
as well (Borod et al., 1993; Feinberg et al., 1986). This supports the idea of a
generalized deficit in facial processing in schizophrenia. In contrast, differential
deficits for emotional discrimination were observed by Cutting (1981) and Novic
(1984), who studied chronic schizophrenics and found a differential emotion dis-
crimination deficit when compared with color, facial, and age recognition.
Heimberg et al. (1992) likewise reported differential impairment in discrimina-
tion of happy and sad facial expression relative to age discrimination (Fig. 17.4).
Improvement of performance has been reported in patients with major depres-
sion after treatment response (Mikhailova et al., 1996), however, the deficit may
be stable in schizophrenia (Gaebel & Wolwer, 1992).
Treatment Interventions
Treatment for schizophrenia is in large part aimed at improvement and preven-

tion of acute psychotic symptoms, which tend to respond to neuroleptics. Emo-
tional dysfunction in schizophrenia has received limited attention, apparently be-
cause acute psychotic symptoms overshadow less dramatic symptomatology. In
addition, emotional dysfunction, similar to neuropsychological impairment, can
be viewed as a trait of the illness that may precede the onset of psychotic symp-
toms and may not change with treatment. This is underscored by increased evi-
Figure 17.4. Sample items of faces with happy and sad expressions.
dence for neurodevelopmental aberrations in schizophrenia. For example, a ret-

rospective study of childhood home videos obtained from adults currently suf-
fering from schizophrenia showed difficulties in relatedness and slowed motor
development (Walker et al., 1993).
Depression
Studies on treatment of depression in schizophrenia have suffered from the

methodological limitations inherent in assessing and quantifying depression in
schizophrenia. All studies evaluating the presence of depressed mood in patients
with acute psychosis report improvement with remission regardless of the use of
antidepressant medication. Most studies have centered on the treatment of de-
pressive symptoms in chronic institutionalized patients, and only a few have ex-
amined the role of antidepressant treatment in patients suffering from an acute
episode.
Two comprehensive reviews (Plasky, 1991; Siris, 1991) of the literature on
depressive symptoms in schizophrenia evaluated over 30 publications and found
only three articles that clearly support the benefit of antidepressant treatment.
Many studies were difficult to interpret due to flawed designs. Plasky (1991) re-
viewed the literature on antidepressant use in schizophrenia by analyzing seven
studies published between 1979 and 1990 and briefly reviewing several others.
Some studies were limited by inadequate assessment of depression (Waehrens &
Gerlach, 1980), small number of patients (Goff et al., 1990), retrospective chart
review with no quantification of depressed mood (Siris, Rifkin, & Reardon, 1982),
and comparative patient groups with markedly different psychosis scores (Pru-
soff et al., 1979). It appears that tricyclic antidepressants are beneficial for treat-
ing symptoms of depression in schizophrenia once the psychosis is stabilized
(Prusoff et al., 1979; Siris et al., 1982, 1987), but can worsen psychotic symp-
toms (Dufresne, Kass, & Becker, 1988; Kramer, Vogel, & DiJohnson, 1989; Pru-
soff et al., 1979) and may have no effect on negative symptoms of schizophre-
nia (Becker, 1983; Waehrens & Gerlach, 1980).
Siris (1991) reviewed 29 studies published between 1972 and 1989 that de-
scribe the prevalence and treatment of secondary depression in schizophrenia, in-
cluding nine double-blind studies of antidepressants. Six studies described stan-
dard criteria for the diagnosis of schizophrenia and scales to evaluate depression,
consisting of the Diagnostic and Statistical Manual, Research Diagnostic Crite-
ria, Feighner (1981), Hamilton Rating Scale for Depression, and Beck Depres-
sion Inventory. Only one study (Siris et al., 1987) showed unequivocal im-
provement of mood on antidepressant medication, as imipramine was superior
to placebo with improvement of depressive symptoms in patients with schizo-
phrenia or schizoaffective disorder who had stable psychotic symptoms. Other
studies that show an apparent beneficial effect of antidepressant medication are
flawed in the selection of patients who had previously responded to antidepres-

sant treatment (see Siris et al., 1994) or had a high placebo response (Johnson,
1981). Studies indicating a beneficial effect of antidepressants included patients
who were treated as outpatients or exhibited more stable psychotic symptoms.
Siris (1991) concluded that antidepressants are without benefit for patients with-
out clear depressive symptoms or with florid psychotic symptoms and of ques-
tionable or limited benefit for chronic inpatients and patients with unstable psy-
chotic symptoms.
Over the last 10 years, atypical neuroleptics that affect serotonergic pathways
have been used widely in the treatment of schizophrenia. Of this group of med-
ications, clozapine and olanzapine have been investigated for specific antidepres-
sant effects in schizophrenia and mood disorders (Ranjan & Meltzer, 1996; Weisler
et al., 1997; Zarate, Tohen, & Baldessarini, 1995). In a large cohort of patients with
acute exacerbation of chronic schizophrenia, at least an average dose of olanzap-
ine was found to improve anxious and depressive symptoms compared with placebo
and haloperidol. This effect was found to be independent of improvement in pos-
itive, negative, and extrapyramidal symptoms (Tollefson et al., 1998a,b). Likewise,
clozapine has been described to have a beneficial effect on depressive symptoms
(Abraham et al., 1997) and suicidality (Meltzer & Okayli, 1995).
Negative symptoms
Over the past 10 years, there has been an increasing understanding that nega-
tive symptoms represent characteristic symptoms of schizophrenia, which persist
throughout the course of illness, are more common in men, and have marked con-
sequences on the person's social and interpersonal functioning. While positive
symptoms of schizophrenia—hallucinations, delusions, and disordered thinking—
are responsive to treatment with standard neuroleptic medications, negative symp-
toms—flat affect, alogia, and anhedonia—are less readily treated, and in fact,
may worsen as a side effect of dopaminergic blockade. About 10 years ago, Tan-
don, Greden, and Silk (1988) showed that trihexyphenidyl, a commonly used an-
ticholinergic agent, improved negative symptoms in a small series of patients.
Subsequent studies revealed standard haloperidol treatment to improve negative
symptoms independent of positive symptoms (Palao et al., 1994) and even in
previously neuroleptic naive schizophrenia patients (Labarca et al., 1993), al-
though at a slower rate than positive symptoms. With the advent of atypical neu-
roleptics, clozaril (Miller et al., 1994) and, more recently, olanzapine (Tollefson
& Sanger, 1997) were found to improve prominent negative symptoms compared
with haloperidol and placebo; however, the effect on negative symptoms remains
disputed (Buchanan et al., 1998). The effects of the newer, antipsychotic med-
ications are thought to occur through complex pleotropic interactions targetting
multiple neurotransmitters, including serotonin systems. Similarly, fluvoxamine,
a specific serotonin reuptake inhibitor, has been reported to improve prominent
negative symptoms compared with maprotiline, a noradrenergic antidepressant

(Silver & Shmugliakov, 1998).
NEUROBIOLOGICAL STUDIES OF EMOTIONAL PROCESSING
The introduction of neurobiologic studies for advancing the understanding of

emotion-related symptoms in schizophrenia has lagged behind neurocognitive re-
search. Advanced methods in the study of emotional processing have been ap-
plied to schizophrenia, as summarized above. There are important gaps and a
need for more research.
Brain metabolism and blood flow studies in patients with major depression
have described decreased metabolism in the left inferior frontal lobe (positron
emission tomography with fluorodeoxyglucose [FDG-PET]; Baxter et al., 1985;
Dolan & Friston, 1989), left anterior cingulate (single photon emission computed
tomography with hexamethyl-propylene amine oxime; Mayberg et al., 1994), and
caudate nuclei (Baxter et al., 1985). Similar findings have been found for de-
pressed patients with Parkinson's disease (Mayberg et al., 1990), Huntington's
chorea (Mayberg et al., 1992), stroke (Robinson et al., 1984) and complex par-
tial seizures (Bromfield et al., 1992). From these neuroimaging studies it appears
that idiopathic depression and depression in other neurological disorders involve
a disequilibrium of left compared with right anterior hemispheric structures, in-
cluding limbic circuitry
We evaluated 79 patients who were grouped according to their ratings on the
Hamilton Rating Scale for Depression: 18 was the cutoff between the schizo-
phrenia depression and schizophrenia control groups. All patients underwent clin-
ical and MRI evaluation, and a subsample of 37 underwent FDG-PET measure-
ments of cerebral glucose metabolism (Kohler et al., 1998b). Patient groups with
and without depression did not differ in the demographic variables of sex, race,
age at evaluation, and education. Furthermore, there were no differences in the
clinical variables of diagnosis (schizophrenia, schizophreniform), medication sta-
tus (neuroleptic naive, previously medicated), age at onset of schizophrenia, du-
ration of illness, or number of hospitalizations. Regarding symptoms, there was
no main effect due to depression group, but there was a negative versus positive
symptoms by subscale by depression group interaction (F = 3.37; df = 3,231;
P = 0.02). This was because patients in the schizophrenia with depression group
were rated higher on alogia and lower on delusions. No other subscale showed
a difference between the groups, nor did the groups differ in ratings of quality
of life.
The schizophrenia with depression group had larger bilateral temporal lobe
volumes and decreased laterality (left minus right) of metabolism in the anterior
cingulate. The neuroanatomic findings (Fig. 17.5) suggest that depression in
Figure 17.5. Temporal lobe brain and cerebrospinal fluid (CSF) volumes by depression
group (high depression, N = 40; low depression, TV = 39). Schizophrenia patients with
depression have larger temporal lobe volumes. (Reprinted with permission from Kohler
et al, 1998b.)
schizophrenia is associated with higher volume of the temporal lobe. Indeed, un-
like their counterparts with low depression, whose temporal lobe volumes were
significantly reduced compared with healthy controls, the high depression pa-
tients with schizophrenia had normal volumes. This finding further buttresses the
position that depression in schizophrenia is distinct from primary negative symp-
toms. Our earlier studies have shown that deficit patients with schizophrenia have
smaller temporal lobe volumes than nondeficit patients (Turetsky et al., 1995).
Furthermore, in the current sample, the more depressed group had lower ratings
on alogia and larger temporal lobe volumes. The association of depression with
normal temporal lobe volumes in schizophrenia suggests that some integrity of
the temporal lobe is necessary for the experience of depression, consistent with
evidence for the role of the temporal lobe in emotional experience.
In the subsample of patients who had FDG-PET measures of cerebral glucose
metabolism, the patient group with higher depression ratings had reduced left lat-
eralization of metabolism in the anterior cingulate (Fig. 17.6). Whereas healthy
subjects show relatively higher left hemispheric metabolism in this region, this
gradient is somewhat diminished in the high depression group and increased in
the low depression group. Thus, depression in schizophrenia seems associated
with a relative decrease in left compared with right cingulate activity. This is
consistent with evidence for greater right hemispheric involvement in dysphoric
states in lesion studies (Gainotti, 1972; Robinson et al., 1984; Ross & Mesulam,
1979; Sackeim et al., 1982), as well as in studies of healthy people (Davidson et
al., 1990; Davidson & Tomarken, 1989; Natale, Gur, & Gur, 1983; Sackeim,
Figure 17.6. Laterality of 18-fluorodeoxuglucose (FDG) PET metabolism by depression

group (high depression, N = 19; low depression, N = 18). Depressed schizophrenia pa-
tients have relative hypometabolism in the left anterior cingulate. DM, dorsal medial pre-
frontal; DL, dorsal lateral prefrontal; IF, inferior frontal; OF, orbital frontal; RG, rectal
gyrus; ST, superior temporal; MT, midtemporal; IT, inferior temporal; AC, anterior cin-
gulate; CN, caudate nucleus; TH, thalamus. (Reprinted with permission from Kohler et
al., 1998b.)
Gur, & Saucy, 1978). The cingulum and mesial temporal regions form the lim-
bic lobe (Broca, 1878), the instrumental part of the neural circuitry responsible
for emotional processing (Papez, 1937). Our findings indicate that the neurobi-
ology of depression in schizophrenia has features in common with major
depression and depression associated with other brain disorders. Specifically,
this involves altered function of frontal regions as measured by lateralized
metabolism.
SUMMARY
In this chapter, we provide a historical overview of the concepts of emotional

processing; clinical features of expression, experience, and recognition of emo-
tions; and treatment interventions with a focus on affective states in the illness
of schizophrenia. Although schizophrenia has been traditionally considered a dis-
order of cognition, disturbed affect has been implicated from the outset, and there
is increased evidence for its major role. To the extent that disturbed affect is a
core negative symptom, its presence in a patient is an ominous sign, foreboding
poor course and treatment response. On the other hand, disturbed affect in the
form of depression or, less frequently, manic symptoms may indicate a more pal-
liable form of psychosis. To this extent we describe similarities in cognition and
brain metabolism of depression in schizophrenia compared with idiopathic de-
pression as well as depression in other brain-related disorders and link the pres-
ence of depression in schizophrenia with preserved temporal lobe volume, indi-
cating preserved anatomy of limbic structures.
In the future, research in the area of emotional expression may include at-
tempts at amelioration of affective flattening via rehabilitation and pharma-
cotherapy that target serotonergic neural substrates. Future investigations in emo-
tional experience in schizophrenia may include further evaluation of whether
depression during different phases of acute and chronic schizophrenia will more
favorably respond to atypical rather than to typical antipsychotic or perhaps an-
tidepressant medication. Conversely, it is not known whether mood stabilizers
may ameliorate symptoms of mania in schizophrenia. With respect to emotion
recognition, research may be directed at further investigations on the controver-
sial concept of a specific emotion recognition deficit in schizophrenia by devel-
oping a visuospatial control task that differs in the component of emotion recog-
nition only. Another question is whether deficits in emotional processing
represent a stable deficit in schizophrenia or whether such deficits can be ame-
liorated via treatment of positive or negative symptoms of schizophrenia. Finally,
neurobehavioral probes evaluating neuronal activation during emotional pro-
cessing may further elucidate the question of whether emotion recognition rep-
resents a specific impairment in the illness of schizophrenia.
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18
Therapeutic Brain Interventions in Mood
Disorders and the Nature of Emotion
SARAH H. LISANBY AND HAROLD A. SACKEIM
The introduction of convulsive therapy (ECT) in the 1930s and psychotropic

medications in the 1950s changed the face of therapeutics in psychiatry. Be-
fore the development of these somatic treatments, the predominant view was
that the major forms of psychopathology reflected irreversible structural de-
generation of the brain and that little could be done to ameliorate symptoms.
The discovery of effective somatic therapies did more than undo this thera-
peutic nihilism. It provided fertile ground for nosological refinement and for
the generation of hypotheses regarding the mechanisms of action of the treat-
ments and the underlying pathophysiology of specific disorders (Fink, 1979;
Klein et al., 1980).
We attempt to summarize the implications of the knowledge gained in the
treatment of mood disorders for theories about the neurobiological regulation of
emotion. The four brain interventions examined include: (7) psychopharmaco-
logical treatments, (2) ECT, (3) functional neurosurgery, and (4) repetitive trans-
cranial magnetic stimulation (rTMS). These interventions have mood-altering ef-
fects but differ in their mechanisms of action and degree of anatomical specificity.
Other brain interventions, including light therapy and sleep deprivation, have
contributed to our understanding of mood systems but are beyond the scope of
this chapter.
456
Therapeutic Brain Interventions in Mood Disorders 457
PSYCHOPHARMACOLOGICAL TREATMENTS
Pharmacological Dissection
The differential efficacy of pharmacological treatments has been fundamental in

subtyping mood disorders and generating a refined nosology. The first distinction
was between unipolar and bipolar disorders. Traditional antidepressant medica-
tions, such as tricyclic antidepressants (TCAs), monoamine oxidase inhibitors
(MAOIs), and selective serotonin reuptake inhibitors (SSRIs), effectively treat the
depressed phase of bipolar disorder but may provoke hypomania or mania. These
agents rarely provoke these reactions in patients with an established unipolar course.
Mood-stabilizing agents, principally lithium carbonate, and/or a variety of anti-
convulsant medications (e.g., carbamazepine and sodium valproate) are effective
antimanic agents (Goodwin & Jamison, 1990). Other research confirmed that unipo-
lar and bipolar disorders differ in familial transmission, onset, and clinical course
(Angst, Felder, & Frey, 1979; Gershon et al., 1982). These findings provided prima
facie evidence that the pathophysiologies of depressed and manic states were dis-
tinct. Additionally, bipolar and unipolar patients differ in key symptomatic mani-
festations during the depressed phase. For example, psychomotor retardation is
more common in bipolar than in unipolar depression (Sobin & Sackeim, 1997).
Differential pharmacological response has been used to subtype unipolar de-
pression. Patients with delusional or psychotic depression respond poorly to
monotherapy with antidepressant medications (TCAs, MAOIs, or SSRIs) (Chan
et al., 1987; Glassman, Kantor, & Shostak, 1975). Such patients also have a poor
response to monotherapy with antipsychotic medication (Spiker et al., 1985) but
show robust rates of response to combination treatment with an antidepressant
and antipsychotic medication (Perry et al., 1982; Spiker et al., 1985) or ECT
(Sobin et al., 1996). This distinction between delusional and nondelusional de-
pression is supported by differences in other aspects of phenomenology, family
history, and suicide rate (Glassman & Roose, 1981; Roose et al., 1983). The phar-
macological evidence implies that abnormalities in dopaminergic systems are
more central to delusional than to nondelusional depression.
Among nondelusional depressed patients, further distinctions may be drawn.
Atypical depression presents with increased sleep (hypersomnia), increased ap-
petite (hyperphagia), marked fatigue ("leaden paralysis"), and/or rejection sensi-
tivity. These patients respond well to MAOIs and perhaps to SSRIs, but have
low response rates to TCAs (Liebowitz et al., 1984,1988; Quitkin, 1992; Quitkin
et al., 1988). This suggests that noradrenergic dysregulation is less relevant to
atypical than to typical major depression, and the former may have more promi-
nent abnormalities in serotonin and/or dopamine transmission.
Finally, there is evidence to distinguish melancholic or severe depression from
nonmelancholic or less severe presentations (for review, see Rush & Weis-
senburger, 1994). Melancholic, endogenous, or vegetative features among inpa-

tients have predictive value regarding response to TCAs (Abou-Saleh & Cop-
pen, 1983; Gibbons, Clark, & Davis, 1982; Kiloh, Ball, & Garside, 1962; Reisby
et al., 1977). Presently there is controversy as to whether SSRIs are inferior to
TCAs in the treatment of severe, melancholic depression (Roose et al., 1994). In
part because of this controversy and its neurobiological implications, newer an-
tidepressant agents, such as venlafaxine and mirtazapine, were designed to tar-
get multiple neurotransmitter systems (e.g., norepinephrine and serotonin) in an
attempt to be more effective for a broader range of depressed patients than the
SSRIs.
These examples of pharmacological dissection illustrate that the pathophysi-
ology of mood disorders is likely to be heterogeneous. It is hazardous to claim
that the mechanisms involved in a treatment intervention are necessarily related
to the etiology or pathophysiology of the disorder being treated. For example, no
one contends that depressed patients respond to ECT because the lack of a seizure
is intrinsic to their pathophysiology. Individuals sharing certain phenomenolog-
ical features, however, often respond to different pharmacological regimens. In
some cases, there are also established differences in familial transmission, clin-
ical course, and associated biological abnormalities.
Given the heterogeneous pathophysiology of affective disorders, the general-
izability of neurobiological studies of normal variation in mood to clinical sam-
ples becomes tenuous. A central aim of mood provocation studies in normal
samples is to relate biological effects to global descriptors of mood, such as de-
pression, anxiety, and elation. Given the likely heterogeneity of depressed pa-
tient groups, the relevance of such data and the models they generate for under-
standing mood disorders are highly inferential.
Phases of Mood Disturbance
A key principle in the biological treatment of mood disorder is that effective so-
matic treatments suppress symptom manifestations but have little impact on the
underlying disorder. This perspective originally emanated from study of the phar-
macological prevention of relapse and recurrence. A classic set of studies demon-
strated that approximately 50% of patients will relapse within a 6-month period
if antidepressant medication or ECT is discontinued at the point of clinical re-
sponse (Imlah, Ryan, & Harrington, 1965; Kay, Fahy, & Garside, 1970; Mind-
ham, Howland, & Shepherd, 1973; Seager & Bird, 1962). Among medication-
resistant patients who respond to ECT, our ongoing placebo-controlled research
suggests that this relapse rate actually may be closer to 85% in the absence of
continued somatic therapy. In contrast, there is overwhelming evidence that con-
tinuing the antidepressant regimen that produced remission reduces the 6-month
relapse rate to about 20%.
These and related findings call for a distinction among three treatment phases:
acute, continuation, and maintenance (Frank et al., 1990). Acute phase treatment
aims to relieve symptoms. Continuation phase treatment, typically defined as
from 6 to 12 months following symptomatic response, aims to suppress symp-
toms until the underlying episode spontaneously remits (Prien & Kupfer, 1986).
The presumption is that the average duration of episodes is approximately 6 to
9 months, but this is subject to considerable individual variation. Maintenance
treatment aims to prevent the recurrence of a new episode after the original
episode has resolved (Frank et al., 1991).
Robust evidence from pharmacological trials supports these distinctions. Ap-
proximately 50% or more of patients with unipolar major depression will expe-
rience a recurrence within their lifetime. Long-term maintenance treatment with
antidepressant regimens that produced the acute phase clinical response are ef-
fective in preventing recurrence (Frank et al., 1990; Prien et al., 1984). The ef-
ficacy of lithium carbonate in preventing episodes of both depression and mania
is, in many respects, more impressive than its efficacy as acute treatment, par-
ticularly for depression (Calabrese, Bowden, & Woyshville, 1995).
The differential activity of psychopharmacological agents in the different
phases of treatment suggests that attention be paid to the neurobiological distur-
bances (state, episode, and trait markers) specific to these phases. Distinctions
may be made among the neural alterations associated with acute affective symp-
toms (state), the vulnerability to manifest symptoms through a sustained, but self-
limited, period (episode), and the vulnerability to experience affective episodes
(trait). During acute phase treatment, medications act on neural substrates re-
sponsible for symptom expression (state). A more fundamental biological dis-
turbance, however, goes unabated despite treatment, only to resolve sponta-
neously (episode). Finally, another class of biological disturbance triggers single
or recurrent episodes (trait).
Neurobiological investigations are only beginning to make these distinctions
and to outline candidate markers for the distinct phases of mood disturbance. For
example, measures of the activity of the hypothalamic-pituitary-adrenal axis or
hypothalamic-pituitary-thyroid axis commonly show dysfunction during the
state of major depression (Carroll, 1982; Prange, Garbutt, & Loosen, 1987). There
is evidence that while most patients show normalization in some of these mea-
sures following response to acute phase treatment, continued abnormality is pre-
dictive of relapse (Holsboer, 1995). Consequently, such measures have some sen-
sitivity as episode markers. Potential episode or trait markers include global and
topographic disturbances in regional cerebral blood flow (rCBF), which in some
cases have been found to persist independent of remission status (Nobler et al.,
1994; Sackeim et al., 1990). There is evidence that specific neuropsychological
profiles also characterize mood disorder patients independent of symptomatic sta-
tus and are seen in children of bipolar probands before the onset of affective
episodes (Decina et al., 1983; Sackeim et al., 1992a). These likely reflect trait
markers.
It is common in basic emotion research to distinguish between state and trait
neurobiological factors. For example, among normal individuals, Davidson
(1995) has associated persistent lateralized electroencephalographic (EEG) pat-
terns to individual differences in emotional reactivity to provocations, thus link-
ing a lateralized trait phenomenon to a propensity for specific affect states.
Effects of Pharmacological Agents on the Regulation of Emotion
Antidepressant agents are not euphoriants. Normal subjects administered TCAs,

MAOIs, SSRIs, or other effective antidepressants do not experience elation. This
is supported by the fact that such medications are rarely the objects of abuse.
Furthermore, euphoriants or stimulants, like amphetamine, have only a minor
role in the treatment of major depression (Hare, Dominian, & Sharpe, 1962; Thase
& Rush, 1995). Only in the case of bipolar disorder is there a propensity for an-
tidepressant agents to trigger hypomania or mania. Similarly, antimanic agents,
such as lithium and anticonvulsants, do not elicit depressed mood in normal
subjects.
One implication of these observations is that the systems subserving the states
of depression and mania in clinical samples are not, in ordinary circumstances,
mutually inhibitory. In unipolar depression, suppressing symptoms with antide-
pressant medication does not provoke euphoria, regardless of the intensity of
treatment. This would contradict one version of the original valence hypothesis,
at least with respect to mood disorders. This hypothesis suggested that mutually
inhibitory neural systems regulate the expression of positive and negative mood
states (Sackeim et al., 1982). The evidence from pharmacology is that, for the
most part, one class of symptoms can be suppressed without provoking the other.
The effect of antidepressant and antimanic agents on normal variations in mood
has received surprisingly little attention. Anecdotal evidence suggests that anti-
depressant medications do not seem to interfere with the normal dysphoric
response to negative life events. Likewise, there is no evidence that mood-
stabilizing agents, such as lithium or the anticonvulsants, reduce the normal range
of happiness or sadness. These observations imply that psychotropic medications
effective in the treatment of mood disorder act at a neurobiological level re-
sponsible for symptom manifestation, leaving the neural systems responsible for
normal mood reactivity intact. In turn, this suggests that there are fundamental
differences in the neural systems that regulate normal variation in mood and that
are dysregulated during the state of major depression and mania. This implies
that studies of physiological alterations during normal states of sadness and hap-
piness are of limited relevance to understanding the pathophysiology of major
depression and mania (and vice versa). It is noteworthy that the initial tomo-
graphic brain imaging studies of mood provocation in normal people and of the
resting state in major depression and mania have yielded dramatically different
profiles of rCBF effects (for a review of clinical studies, see George et al., 1995a;
Pardo, Pardo, & Raichle, 1993; Sackeim & Prohovnik, 1993; Schneider et al.,
1994).
A number of pharmacological interventions can induce euphoria in normal
subjects. These are the most common drugs of abuse and include stimulants, co-
caine, and opioids. Barbiturates and alcohol are classified as central nervous sys-
tem depressants but are commonly abused, like benzodiazepines, due to their
anxiolytic properties. As reviewed elsewhere (Sackeim, 1986), there have been
concerted attempts for several decades to identify pharmacological agents that
reliably induce clinical depression or simply depressed mood state in normal sub-
jects. These efforts have mostly failed. This would suggest a fundamental, as yet
unidentified, difference in the substrates regulating depressed and elated mood
states in normal individuals.
Mechanisms of Action and the Pathophysiology of Mood Disturbance
Antidepressants differ widely in their intrinsic pharmacological properties. TCAs,

MAOIs, SSRIs, and a variety of newer compounds, however, possess roughly
equivalent efficacy for nonpsychotic, nonatypical, major depression (Burke &
Preskorn, 1995). Although there are numerous examples of patients who respond
to one but not another type of antidepressant within or outside of the same class,
this is the exception rather than the rule. Does this suggest that there is a com-
mon mode of action across these agents despite differing pharmacological pro-
files, or are there multiple avenues to relieve symptoms?
The possibility of a common mode of antidepressant action, despite differ-
ences in pharmacological effects, should not be discounted. Almost all effective
antidepressants share a similar time course of action and result in a common set
of neurobiological changes, such as downregulation of the postsynaptic /32-adren-
ergic receptor and/or upregulation of the postsynaptic serotonin 5HT2 receptor
and the gamma-aminobutyric acid (GABA) GABAb receptor (Gerner & Bunney,
1986; Heninger & Charney, 1987; Lloyd, Morselli, & Bartholini, 1987). The ma-
jor neurotransmitter systems implicated in the treatment of mood disorders, no-
radrenergic, dopaminergic, serotonergic, and GABAergic, strongly interact. Cere-
brospinal fluid studies of transmitter metabolite levels have shown considerable
overlap in the effects of different classes of pharmacological agents (Potter &
Manji, 1993).
Nonetheless, there is also compelling evidence to support specificity in the
mode of action of pharmacological treatments in achieving antidepressant re-
sponse. Dietary tryptophan depletion rapidly decreases brain levels of tryptophan
(precursor to serotonin), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA, a
metabolite of serotonin). In formerly depressed patients who were successfully

treated with an SSRI, tryptophan depletion results in rapid, transient relapse
(Bremner et al., 1997; Delgado et al., 1990). Tryptophan depletion also disrupts
the response to light therapy in seasonal affective disorder (Neumeister et al.,
1997). It does not, however, appear to worsen symptoms in untreated depressed
patients (Delgado et al., 1994), nor does it provoke relapse in patients who have
responded to a TCA (Heninger, Delgado, & Charney, 1996) or ECT (Cassidy et
al., 1997). There is initial evidence for a double dissociation between serotoner-
gic and noradrenergic manipulations; transient relapse in patients who responded
to a TCA, but not to an SSRI, may be provoked by depleting noradrenergic stores
(Delgado et al., 1993).
This experimental reversal of therapeutic effects contingent on the form of
treatment that produced the response provides impressive evidence for specificity
in mechanisms of action. It suggests that SSRIs differ from TCAs and ECT in
how antidepressant effects are accomplished. In turn, this suggests that multiple
neurobiological substrates (or nodes within a network) can be altered to suppress
depressive symptoms. Given this diversity in the modes of therapeutic action,
one must entertain the possibility that multiple physiological alterations may re-
sult in a unitary presentation of depressed mood in normal individuals and/or
clinical depression.
ELECTROCONVULSIVE THERAPY
Convulsive therapy involves the deliberate induction of a generalized, grand mal

seizure for therapeutic purposes and is the biological treatment with the longest
history of continuous use in psychiatry. Indications include major depression,
acute mania, and schizophrenia (Weiner et al., 1990). It is generally acknowl-
edged that convulsive therapy is the most potent antidepressant treatment and
that a substantial number of patients with medication-resistant depression show
considerable benefit from its use (Prudic et al., 1996). Similarly, the short-term
efficacy of convulsive therapy in mania is well established and may equal or ex-
ceed its potency as an antidepressant (Mukherjee, Sackeim, & Schnur, 1994).
Given the substantial evidence implicating dysregulation of distinct neurobio-
logical systems in major depression and mania, the efficacy of ECT in both con-
ditions requires consideration (Post et al., 1986).
When convulsive therapy was introduced in the mid-1930s, seizure induction
was accomplished through systemic injection of proconvulsant agents. Electro-
convulsive therapy involves the application to the scalp of a time-varying elec-
trical stimulus of sufficient intensity to produce a generalized seizure. Electro-
convulsive therapy replaced chemical induction because of its greater medical
safety and control over the timing and likelihood of seizure. In the 1950s, it was
appreciated that application of the electrical stimulus to the left or right hemi-
sphere (i.e., left unilateral [LUL] or right unilateral [RUL] ECT), resulted in dis-
tinct short-term cognitive sequelae (Sackeim, 1992). For example, each form of
ECT results in a material-specific amnestic syndrome, with greater verbal loss
following LUL ECT and greater nonverbal memory loss following RUL ECT
(Sackeim, 1992). The magnitude and consistency of the differences in transient
neuropsychological effects between LUL and RUL ECT are sufficiently robust
that the nature and direction of language lateralization can be reliably determined
on a patient-by-patient basis (Geffen, Traub, & Stierman, 1978; Pratt & War-
rington, 1972). Bilateral (BL) ECT, with symmetrical placement of stimulating
electrodes over frontotemporal areas, results in the cognitive deficits associated
with both forms of unilateral ECT, perhaps to a more severe and persistent de-
gree (Sackeim, 1992; Sackeim et al., 1993b). The capacity to manipulate the site
of brain stimulation by the positioning of extracranial electrodes in ECT offers
one method to investigate the neural systems dysregulated in mood disorders.
Efficacy of Electroconvulsive Therapy: Generalized or

Localized Effects?
For decades, the field of ECT held the view that a generalized seizure was nec-
essary and sufficient to treat major depression. How the seizure was produced
was considered irrelevant (Small, 1974). Furthermore, it was thought that the
quantity of electricity used to produce the seizure did not impact on efficacy but
did contribute to cognitive side effects (Sackeim, Devanand, & Nobler, 1995).
A large body of literature had shown that markedly suprathreshold electrical stim-
ulation intensifies side effects without additional benefit (Ottosson, 1960; Scott
et al., 1992; Weiner et al., 1986b).
Competing hypotheses have been put forth to explain the view that generalized
seizure activity is central to the therapeutic effects of ECT. One hypothesis was
that for therapeutic effects to be achieved, widespread, generalized changes in brain
neurochemistry were necessary. The alternative hypothesis was that localized brain
systems were involved, but their neurobiology could only be altered with ECT by
engagement of a generalized seizure. Drawing a link between hypothalamic dys-
function and the vegetative symptoms of melancholic depression (sleep and ap-
petite disturbance, diurnal variation, reduced libido), many theorists argued that the
ultimate source of ECT's therapeutic effects resulted from neurochemical changes
in the diencephalon (Abrams, 1997; Abrams & Taylor, 1976; Fink, 1990).
There is substantial evidence that a generalized seizure is critical in obtaining
therapeutic effects with ECT. A series of studies contrasted "sham ECT" (the re-
peated administration of general anesthesia) with real ECT. This work established
that in the treatment of major depression (for review, see Sackeim, 1989) or acute
mania (Sikdar et al., 1994), real ECT is considerably more effective than sham.
This type of study controls for psychological factors surrounding ECT, includ-
ing the high expectations for remission, and indicates that the passage of elec-
tricity and/or the production of a seizure are central to efficacy. Other work went
a step further and compared ECT with subconvulsive electrical stimulation, which
was found to be substantially less effective (Fink, Kahn, & Green, 1958; Ulett,
Smith, & Glesser, 1956). Ottosson (1960) provided one of the most influential
pieces of evidence that the generalized seizure is critical. He found that pre-
treatment with lidocaine, which reduced seizure expression, resulted in inferior
clinical outcome. Finally, electrical and chemical seizure induction appeared to
have equal efficacy, suggesting that methods of seizure elicitation are irrelevant
to beneficial effects (Small, 1974).
Despite this wealth of evidence, recent research has challenged the view that
a generalized seizure is both necessary and sufficient for antidepressant effects
(Sackeim et al., 1993b). This research implies that the current paths traversed by
the electrical stimulus, and the current density within those paths, fundamentally
impact on the efficacy of the treatment (Sackeim, 1994a). Consequently, there is
now convincing evidence for neuroanatomical specificity in the neural systems
that must be altered for ECT to exert antidepressant effects.
Technical Factors and the Efficacy of Electroconvulsive Therapy
Until recently, standard ECT practice involved administering the same electrical
dosage to all patients. Methods to quantify the threshold for a generalized seizure
were only developed in the last decade (Sackeim et al., 1987c). The field also
lacked information on the extent of individual differences in seizure threshold
and the factors that determine this variability (Sackeim et al., 1994; Sackeim,
Devanand, & Prudic, 1991; Weiner et al., 1990).
It is now evident that there are marked individual differences in seizure thresh-
old (Lisanby et al., 1996; Sackeim et al., 1994; Sackeim, Devanand, & Prudic,
1991). Fixed dosage regimens often result in grossly suprathreshold stimulation
and increased cognitive side effects. Another consequence of this practice was a
failure to appreciate that, combined with electrode positioning, electrical dosage
could have a profound effect on efficacy.
The first study to address this issue used a double-blind, randomized design
in which patients with major depression were treated with either BL or RUL
ECT, with electrical intensity maintained just above seizure threshold (Sackeim
et al., 1987a). The surprising outcome of this work was that RUL ECT given just
above threshold was notably deficient as an antidepressant. Seventy percent of
patients randomized to BL ECT were classified as responders, whereas only 28%
of RUL ECT patients were so classified. These findings led to the hypothesis
that the efficacy of RUL ECT was highly sensitive to dosage. Robin and de Tis-
sera (1982) raised the possibility that electrical dosage impacts on speed of clin-
ical response. A subsequent study tested both propositions. Patients with major
depression were randomized to receive either BL or RUL ECT with stimulus in-
tensity just above seizure threshold (low dose) or stimulus intensity 2.5 times the
seizure threshold (high dosage) (Sackeim et al., 1993b). Only 17% of patients
receiving RUL ECT at low intensity responded, but increasing the stimulus in-
tensity of RUL ECT markedly unproved the response rate. This work also demon-
strated that speed of response is enhanced with higher stimulus intensity for both
BL and RUL ECT. In ongoing research at Columbia University, the dose-
response function for RUL ECT is being more carefully defined.
Why Is Low Dosage Right Unilateral Electroconvulsive

Therapy Ineffective?
Research has established that dramatic differences in antidepressant effects are

obtained by varying electrode positioning and stimulus dosage. This implies that
the current paths traversed by the ECT stimulus determine rates of response, im-
plicating specificity in the anatomy of the neural systems involved in the thera-
peutic effects of ECT. It is possible to induce generalized seizures that reliably
lack efficacy. Thus, while a generalized seizure may be necessary, it is not suf-
ficient. Exploring why alterations of stimulus intensity impact on the efficacy of
RUL ECT provides a new approach to elucidate the mechanisms of action of
ECT. Three hypotheses, discussed below, have been offered to account for the
effects of stimulus intensity on the efficacy of RUL ECT (Sackeim, 1994a).
Bilateral seizure generalization

In unilateral ECT, current density is relatively evenly distributed across the
anterior two-thirds of the stimulated hemisphere and approximately three times
greater in the stimulated than nonstimulated hemisphere (Weaver, Williams, &
Rush, 1976). Although LUL and RUL ECT both produce bilaterally generalized
seizures, EEG seizure expression is often greater on the side of stimulation (d'Elia
& Penis, 1970). Other physiological indices are compatible with a profound
asymmetry in functional brain activity. Following unilateral ECT, there is a
marked decrease in rCBF in anterior regions on the side of stimulation, with lit-
tle or no change in the opposite hemisphere (Nobler et al., 1994; Silfverskiold
& Risberg, 1989). Similarly, there is an increase in delta activity in the resting
EEG, most marked over the stimulated hemisphere (Sackeim et al., 1996).
Deficits in learning and memory largely reflect disruption of processing in the
stimulated hemisphere (Sackeim, 1992; Sackeim et al., 1993b).
Some have taken the position that the efficacy of RUL ECT is enhanced at
higher stimulus intensity because the increased electrical dosage results in greater
bilateral seizure generalization, making RUL more like BL ECT (Weiner & Cof-
fey, 1986). A critical implication of this view is that bilateral neurobiological al-
terations are necessary to achieve antidepressant effects, contradicting ideas that

lateralization in the regulation of emotion has relevance for therapeutics, at least
in the context of ECT. This position predicts that physiological and neuropsy-
chological asymmetries are reduced when the stimulus intensity of RUL ECT is
increased. The available evidence does not support these predictions. In fact, EEC
asymmetries during and following seizure induction appear to be somewhat en-
hanced at high relative to low intensity RUL ECT (Krystal et al., 1993; Krystal,
Weiner, & Coffey, 1995; Sackeim et al., 1996). Left-sided neglect in the acute
postictal period, an indicator of right hemisphere disruption, is more consistent
and profound with high intensity than low intensity RUL ECT (Sackeim et al.,
1992b). High intensity RUL ECT does not result in greater acute or short-term
retrograde amnesia for verbal material but increases the amnesia for nonverbal
information (Sackeim et al., 1993b).
Stimulation of deep subcortical structures

At equivalent electrical intensity, BL ECT results in substantially greater cur-
rent density in diencephalic regions than RUL ECT (Weaver et al., 1976). In-
creasing the stimulus intensity of RUL ECT results in greater current density and
perhaps seizure expression in deep subcortical regions. In agreement with clas-
sic views emphasizing hypothalamic effects, it has been argued that this effect
accounts for the increased efficacy of higher dosage RUL ECT (Abrams, 1986,
1997).
Assessment of this possibility is difficult due to the absence of direct markers
of electrical stimulation or seizure propagation to the diencephalon. Nonetheless,
some indirect measures of hypothalamic activity have been examined. ECT re-
sults in an acute surge of plasma hormones, such as prolactin, oxytocin, and va-
sopressin, whose release is mediated by the hypothalamus. Manipulations of elec-
trode placement and stimulus intensity impact on the magnitude of the release
of specific hormones (Devanand et al., 1998; Lisanby et al., 1998a; Zis et al.,
1996). Variations in the magnitude of these hormone surges may not, however,
correlate with efficacy (Devanand et al., 1998; Lisanby et al., 1998a). Likewise,
ECT produces consistent short-term changes in measures of the hypothala-
mic-pituitary-adrenal axis, and these changes are also unrelated to efficacy (De-
vanand et al., 1987, 1991). One could hypothesize that the development of
transcortical slow wave (delta) activity in the interictal EEG reflects an effect on
thalamic pacemakers. This has also, however, been found to be unrelated to ef-
ficacy (Sackeim et al., 1996).
Anticonvulsant action and functional activity in prefrontal cortex

It is well established that ECT is a powerful anticonvulsant (Post et al., 1986;
Sackeim et al., 1983a). Repeated treatment with ECT results in a progressive rise
in seizure threshold and a reduction in both seizure duration and intensity of
seizure expression (Sackeim et al., 1987b). Electroconvulsive therapy results in

acute and short-term topographically distributed changes in functional brain ac-
tivity. There is a decrease in cortical rCBF and regional cerebral metabolic rate
for glucose and a marked increase in slow wave activity in the EEG (Ackermann,
Engel, & Baxter, 1986; Nobler et al., 1994; Weiner et al., 1986a).
Electroconvulsive shock in animal models of epilepsy has shown marked an-
ticonvulsant properties equaling or exceeding numerous anticonvulsant medica-
tions (Babington & Wedeking, 1975; Post et al., 1986) and has been used occa-
sionally in the clinical treatment of seizure disorders (Caplan, 1946; Sackeim et
al., 1983a; Schnur et al., 1989). Electroconvulsive shock increases concentrations
of specific inhibitory neurotransmitters and peptides on a regional basis. The most
likely candidates underlying the anticonvulsant action of ECT include GABA,
endogenous opioid, adenosine, and neuropeptide Y (Sackeim, Devanand, &
Nobler, 1995; Woldbye et al., 1996).
One theory posits that the anticonvulsant effects of ECT underlie both its an-
tidepressant and antimanic properties (Post et al., 1986; Sackeim et al., 1983a).
Unlike conventional antidepressant medications, some anticonvulsants have es-
tablished antimanic properties and some degree of antidepressant effects. Elec-
troconvulsive therapy has marked efficacy in both conditions.
A version of the anticonvulsant hypothesis focuses on the topographic distri-
bution of the increase in inhibitory neurotransmission and the reduction in func-
tional brain activity that accompany ECT. This theory argues that the spatial dis-
tribution of these effects is determined more by the sites of seizure initiation than
by seizure propagation. It is claimed that at low dosage, RUL ECT results in
seizures that initiate in the motor cortex. At higher dosages, prefrontal cortical
regions are more likely to be sites of seizure initiation with RUL ECT (Sackeim
& Mukherjee, 1986). Reduction in functional activity in prefrontal regions is con-
sidered essential to the therapeutic effects of ECT in mood disorders (Sackeim,
1994a).
The known variability in seizure threshold across cortical regions may explain
the finding that manipulation of the stimulus intensity of RUL ECT alters the
sites of seizure initiation. Within the cortex, the primary motor area has the low-
est threshold for seizure induction (Sackeim & Mukherjee, 1986). Because cur-
rent density with RUL ECT is relatively evenly distributed over the anterior two-
thirds of the stimulated hemisphere, primary motor cortex is the likely site of
seizure initiation when minimal dosage is used. With a large enough increase in
dose, current density should be sufficient to trigger self-sustaining seizure activ-
ity from prefrontal regions. In contrast, current density with BL ECT is greatest
near the prefrontal pole and drops sharply along the anteroposterior dimension
(Hayes, 1950). The fact that seizures are initiated with BL ECT in prefrontal re-
gions regardless of the stimulus intensity may explain why electrical intensity
has little impact on the efficacy of BL ECT.
Recent brain imaging studies support the theory that reduction of functional
activity in prefrontal cortical regions is linked to the efficacy of ECT. The rCBF
reductions seen acutely and 1 week following ECT typically show an antero-
posterior gradient, with greatest reductions at the prefrontal pole. Most impor-
tantly, this topographic alteration appears to be strongly correlated with thera-
peutic response in both major depression and mania (Nobler et al., 1994).
Likewise, the development of slow wave EEG activity in prefrontal sites shows
topographic specificity in relation to antidepressant effects (Sackeim et al., 1996).
Furthermore, relative to high dosage RUL ECT, low dosage RUL ECT is con-
siderably less likely to enhance prefrontal slow wave activity. Based on such ev-
idence supporting the importance of frontal changes, one group has attempted to
concentrate current density in prefrontal regions, using a bifrontal electrode place-
ment. Preliminary findings suggest that bifrontal ECT may be more effective than
the traditional frontotemporal BL placement and may also result in reduced
amnestic side effects (Lawson et al., 1990; Letemendia et al., 1993).
In summary, the available evidence supports the idea that ECT exerts antide-
pressant, and possibly antimanic, effects through its anticonvulsant properties,
particularly the reduction of functional activity in prefrontal cortical regions. The
emphasis on the role of prefrontal regions is a top-down perspective, suggesting
that functional suppression in prefrontal areas modulates activity in limbic, stri-
atal, thalamic, and hypothalamic regions (Sackeim, 1994a). It should be noted,
however, that anticonvulsant theories, and the specific formulation emphasizing
effects in prefrontal regions, are far from proven. The relevant evidence is largely
correlational, showing associations between the topographic changes in post-ECT
brain imaging measures of functional activity and manipulations of treatment
technique and clinical outcome.
To more directly test these views, key experiments are needed. It may be pos-
sible to block the anticonvulsant properties of ECT with pharmacological ma-
nipulations (Tortella & Long, 1985, 1988). If therapeutic efficacy is unaltered
under such conditions, the anticonvulsant theory would be compromised. It
should also be possible to develop powerful devices that elicit localized seizure
activity with rTMS (Sackeim, 1994b) and at the same time use rTMS to limit
seizure propagation, protecting specific brain systems. Comparing efficacy in pa-
tients randomized to different sites of seizure provocation/inhibition could be a
powerful tool to further define the anatomy of the neural systems subserving the
profound therapeutic effects of ECT.
The Efficacy of Electroconvulsive Therapy and

Lateralization in the Regulation of Emotion
A large body of evidence has documented a special role for right hemisphere
mechanisms in the expression and reception of emotion (e.g., Borod et al., 1986;
Heilman, Scholes, & Watson, 1975; Sackeim, Gur, & Saucy, 1978). Various ver-
sions of the valence hypothesis (Sackeim et al., 1982) suggest that euphoric and
dysphoric mood states reflect alteration of distinct lateralized systems (David-
son, 1995; Liotti & Tucker, 1995; Robinson et al., 1988; Sackeim, 1991). Uni-
lateral ECT results in marked asymmetries in measures of brain activity, neuro-
logical signs (Kriss et al., 1978), and neuropsychological changes indicative of
disruption of lateralized neural systems (Sackeim, 1992). Consequently, the com-
parison of LUL and RUL ECT in antidepressant and antimamc effects is of con-
siderable interest.
LUL ECT results in considerably more prolonged postictal disorientation than
RUL ECT (Daniel & Crovitz, 1982). This fact, and the view that patients prefer
the nonverbal memory deficits following RUL ECT relative to the verbal deficits
of LUL ECT, led to the virtually exclusive use of RUL ECT for unilateral treat-
ment (Weiner et al., 1990). It was not differential efficacy that led to this practice.
A small group of studies compared LUL and RUL ECT in therapeutic prop-
erties (Abrams, Swartz, & Vedak, 1989; Cohen, Penick, & Tarter, 1974; Costello
et al., 1970; Cronin et al., 1970; Decina et al., 1985; Deglin, 1973; Fleminger et
al., 1970; Halliday et al., 1968; Small et al., 1993; Sutherland, Oliver, & Knight,
1969). Most of these studies used nonoptimal ECT technique and were charac-
terized by other methodological problems. The overriding impression from this
work is that both LUL and RUL ECT exert marked antidepressant effects. Al-
though the evidence is inconsistent (Abrams, Swartz, & Vedak, 1989), there are
some indications that RUL ECT may be somewhat superior to LUL ECT in the
treatment of major depression (Cohen, Penick, & Tarter, 1974; Cronin et al.,
1970; Fleminger et al., 1970; Halliday et al., 1968; Small et al., 1993). This would
be compatible with the idea that suppression of functional activity within ante-
rior regions of the right hemisphere has antidepressant effects (Sackeim et al.,
1982).
Whether there is a difference between LUL and RUL ECT in acute mania is
less certain. Initial studies suggested that RUL ECT leads to a worsening of manic
symptoms (Small et al., 1985,1993). In a large retrospective study, however, Black,
Winokur, and Nasrallah (1987) found no difference between RUL and BL ECT.
In a small random-assignment trial, Mukherjee, Sackeim, and Lee (1988) found
that LUL, RUL, and BL ECT were equally effective in medication-resistant manic
patients.
As summarized above, recent research indicates that the spatial distribution of
current density in the brain strongly determines the efficacy of ECT (Sackeim et
al., 1993b). Brain imaging studies examining the topography of changes in rCBF
and EEG slow wave activity have linked reductions in functional activity in bi-
lateral prefrontal regions to the efficacy of ECT for both major depression and
acute mania (Nobler et al., 1994; Sackeim et al., 1996). Studies contrasting LUL
and RUL ECT generally indicate that both exert marked antidepressant effects
yet produce qualitative differences in the nature of cognitive side effects. This
pattern of findings leads to two alternative hypotheses about the role of lateral-
ized mood systems in the pathophysiology of mood disorders and the mecha-
nisms of therapeutic action of ECT.
The first hypothesis is perhaps the most straightforward. Despite a wealth of
evidence concerning lateralization in the regulation of normal mood and in the
precipitation of mood disturbance following brain damage (for review, see Sack-
eim, 1991), the pathophysiology of major mood disorders may not have signif-
icant lateralized components. Indeed, it is conceivable that depression may ini-
tiate with some degree of asymmetry in patterns of functional brain activity but
that, once these states have become autonomous, chronic, and/or severe, the fun-
damental disturbances are bilateral. It is noteworthy that in large-scale studies of
patients receiving ECT, rCBF abnormalities reflected dysregulation of bilateral
networks involving prefrontal, superior temporal, and anterior parietal cortical
regions (Sackeim et al., 1990, 1993a). More generally, tomographic resting stud-
ies of mood disorders have repeatedly demonstrated abnormalities in prefrontal
regions, but findings of frontal asymmetry have been more the exception than
the rule (Sackeim & Prohovnik, 1993). Effective forms of ECT, unilateral or bi-
lateral, may initiate seizures in prefrontal cortex, and it may be that, despite an
asymmetrical initiation with unilateral ECT, tight coupling between left and right
prefrontal regions invariably leads to intense bilateral prefrontal expression of
seizures and subsequent bilateral reduction in functional activity. This hypothe-
sis accounts for the findings of asymmetry in physiological and neuropsycho-
logical measures by noting that such asymmetries largely reflect asymmetrical
impact on more posterior areas. For example, it is generally thought that the ma-
terial-specific amnesia observed following LUL and RUL ECT reflects ipsilat-
eral disruption of medial temporal lobe structures. This hypothesis suggests that
lateralization in the regulation of emotion has little to do with the pathophysiol-
ogy of major mood disorders or their treatment with ECT.
As discussed below, the initial research on nonconvulsive rTMS suggests that
this intervention has antidepressant properties that may depend on the brain re-
gion stimulated. Indeed, there are suggestions that dysregulated lateralized sys-
tems play a key role in the therapeutic effects of rTMS (Pascual-Leone et al.,
1996b). If subsequent research confirms these observation, the tenability of the
hypothesis just offered will be questionable. This is not to say that there is over-
lap in the mechanisms of action of rTMS and ECT. Instead, it is quite likely that
these interventions differ in how they modulate functional brain activity (Sack-
eim, 1994b). The lesson from rTMS, however, may be that it is a more focal in-
tervention capable of selectively altering functional activity in prefrontal regions,
with less impact on homologous, contralateral cortex. A second hypothesis would
stipulate that functional suppression in right prefrontal regions may be necessary
and sufficient to produce antidepressant effects with ECT (and perhaps in left
prefrontal regions for antimanic effects). Present forms of unilateral ECT, be-
cause of patterns of current shunting and intrinsic coupling of prefrontal regions,
produce bilateral effects in the critical regions and misleadingly suggest that lat-
eralization of function is unimportant with respect to therapeutics. Testing these
two rival hypotheses is of considerable theoretical and practical importance and
may become possible with the development of methods to deliver more focal
forms of ECT.
FUNCTIONAL NEUROSURGERY
Overview
Functional neurosurgery is directed at altering the physiology of specific neural

systems for the treatment of psychopathology (Diering & Bell, 1991). This goal
should be distinguished from the surgical resection of abnormal tissue, such as
a tumor, which may produce secondary psychiatric symptoms (Lisanby et al.,
1998b). Previously referred to as psychosurgery, functional neurosurgery is find-
ing new applications for mood, anxiety, and other psychiatric disorders (Yudof-
sky & Ovsiew, 1990). Although originally used extensively for schizophrenia,
functional neurosurgery has generally been found to be more effective for ma-
jor depression and obsessive compulsive disorder (Ballantine & Giriunas, 1979).
History of Functional Neurosurgery for Psychiatric Disorders
Early studies by Papez (1937) identified limbic circuits (regions of the frontal
lobes, cingulate cortex, and subcortical structures) as central to emotion regula-
tion, and it is these limbic structures that are the targets of most neurosurgical
approaches to psychiatric disorders.
First performed by Moniz (1936), frontal leukotomy was introduced in the
United States by Freeman and Watts (1942) (reviewed by Diering & Bell, 1991;
Swayze, 1995). The original procedure involved blind ablation of white matter
tracts underlying prefrontal cortex, whereas the Lyerly (1939) bilateral leukotomy
involved ablation of white matter under direct visualization. Other techniques in-
volved selective ablation of Brodmann's areas 9, 10, and 46 ("topectomy"; Pool
et al., 1949, 1956) and the severing of fibers connecting these areas with the cin-
gulate gyrus (Scoville, 1949). Efficacy was difficult to determine due to method-
ological limitations, such as the lack of stereotactic guidance (May, 1974).
Technical refinements led to more focal lesions (Fulton, 1951) and stereotac-
tic procedures (Spiegel, Wycis, & Freed, 1950). More targeted procedures in-
cluded the thalamotomy (Spiegel, Wycis, & Freed, 1950), cingulotomy (Cassidy,
Ballantine, & Flanagan, 1965; Livingston, 1953; Whitty et al., 1952), subcaudate
tractotomy (Knight, 1965), and limbic leukotomy (combination of cingulotomy

and subcaudate tractotomy; Kelly, Richardson, & Mitchell-Heggs, 1973). Sev-
eral of these early procedures represent precursors of techniques used today (Bal-
lantine & Giriunas, 1979; Ballantine et al., 1987).
Postsurgical Affective Symptoms
Affective symptoms have been described following surgical ablation of limbic

structures for the treatment of nonpsychiatric, as well as psychiatric, conditions.
Apathy and lack of initiative are well-described aspects of frontal lobe syndromes
following frontal leukotomy (Hakola et al., 1993). Depressive symptoms fol-
lowing temporal lobectomy for epilepsy may relate to degeneration of subcorti-
cal structures secondary to deafferentation (Parashos, 1993). Davidson et al.
(1996) reported distinct alterations in emotional arousal following right and left
temporal lobectomy. Transient depression has been reported following thalamo-
tomy (especially left-sided) in the treatment of movement disorders, supporting
the role of thalamolimbic connections in mood symptoms (Angelini et al., 1982;
Broggi, Angelini, & Giorgi, 1980).
Modern Stereotactic Neurosurgical Procedures for

Psychiatric Disorders
Modern Stereotactic approaches have reduced morbidity and produce only tran-
sient effects on attention, without reported long-term effects on neurological sta-
tus, higher brain functions, or personality (Corkin, Twitchell, & Sullivan, 1979;
Maxwell, 1993). Three of the more common procedures (cingulotomy, subcau-
date tractotomy, and anterior capsulotomy) are described below (for review, see
Mindus & Jenike, 1992). Other procedures include amygdalotomy, hypothalam-
otomy, thalamotomy, and various combinations of limbic structures (Ballantine
& Giriunas, 1979).
Anterior cingulotomy
Anterior cingulotomy refers to the bilateral severing of the anterior supracal-
losal fibers of the anterior cingulate, thereby altering connections within the lim-
bic system. This procedure has been reported to have therapeutic effects in mood
disorders (Ballantine et al., 1967, 1987), anxiety disorders (Jenike et al., 1991),
and pain (Foltz & White, 1962). Efficacy is generally higher in major depres-
sion (about 60%) than in obsessive compulsive disorder, and appears after con-
siderable postsurgery delay. Ballantine et al. (1977) reported that 75% of 154 pa-
tients with mood disorder were improved after bilateral cingulotomy. A
retrospective review by Jenike et al. (1991) found that 25%-30% of obsessive
compulsive disorder patients benefitted substantially from cingulotomy. This ben-

efit in obsessive compulsive disorder is thought to be due to interruption of ab-
normal fronto-striatal-thalamic activity, as suggested by positron emission to-
mography (PET) studies (Martuza et al., 1990). The claim that destruction of the
anterior cingulate is associated with antidepressant effects is compatible with
findings from sleep deprivation (Wu et al., 1992), ECT (Scott et al., 1994), and
pharmacological treatment (Bench et al., 1995) indicating reduced functional ac-
tivity in this region concomitant with antidepressant response.
Stereotactic subcaudate tractotomy

Stereotactic subcaudate tractotomy (SST) transects the subcaudate region of
the orbital gyrus, thereby interrupting thalamo-anterior cingulate fibers (Bartlett,
Bridges, & Kelly, 1981; Bridges, 1994; Broseta et al., 1979; Burrows 1994;
Sramka et al., 1992). Knight's procedure (1965, 1969, 1973) involved the im-
plantation of radioactive yttrium (90y) beads. About 70%-80% of depressed pa-
tients were improved, with success rates of around 50% in anxiety disorders
(Broseta et al., 1979; Corkin, Twitchell, & Sullivan, 1979; Martuza et al., 1990).
Bridges et al. (1994) reviewed the results in over 1300 SST procedures and sug-
gested that unipolar depression and a history of good response to ECT were as-
sociated with good SST outcome.
Anterior capsulotomy
Anterior capsulotomy transects the anterior limb of the internal capsule, sev-
ering thalamo-orbitofrontal fibers (Hay, 1993). This may be accomplished via
radiofrequency heat lesions (Bingley et al., 1973) or Stereotactic gamma irradi-
ation (Leksell & Backlund, 1979; Rylander, 1979). Improvement in obsessive
compulsive disorder has been reported (Bingley et al., 1973) with about a 70%
success rate (Martuza et al., 1990). There is some evidence of personality change,
lack of initiative, and mood elevation following capsulotomy (Hay, 1993; Mar-
tuza et al., 1990; Sachdev 1995), and concern about long-term distal effects in
cortex, following large lesions produced with gamma irradiation.
Conclusions
The literature on the use of surgical ablation to treat mood disorders is small,
and, because all procedures other than gamma irradiation involve breaching the
skull, there has been little opportunity for sham controlled comparisons. The ret-
rospective nature of the clinical reports limits certainty about the claims of ther-
apeutic properties. At the same time, it should be recognized that reports of sig-
nificant improvement in a substantial percentage of treatment-refractory patients
deserves attention.
In general, the literature on functional neurosurgery in mood disorders sup-

ports the role of limbic structures in the regulation of emotion. Although the spe-
cific anatomical targets for the various neurosurgical approaches have varied, all
the procedures affect limbic networks, directly or indirectly. This may result in
alterations in the relative activity (e.g., neurophysiological or neurochemical) of
various nodes in this network. In addition, transection of frontolimbic and thal-
amocingulate connections may alter serotonergic and dopaminergic transmission
at sites remote from the lesion (Corkin, Twitchell, & Sullivan, 1979). The asso-
ciation between the time course of mood changes and the appearance of thala-
mic atrophy following frontal leukotomy supports the importance of distal
effects.
Neuroimaging studies may help establish links between the modulation of dis-
ordered networks and the clinical efficacy of stereotactic functional neurosurgery
for mood disorders as has been demonstrated in the case of pallidotomy for
Parkinson's disease (Eidelberg et al., 1996, 1997). Such work may provide an-
other means to isolate the relevant circuits dysregulated in major depression and
may help to select patients likely to respond to particular surgical interventions.
Recently, chronically indwelling electrical stimulators have been used in lieu of
neurosurgery to achieve functional alteration of networks for therapeutic benefit
in central pain syndromes and movement disorders. This approach has been ap-
plied to psychiatric disorders in the past (Escobedo, Fernandez-Guardiolo, &
Solis, 1973) and may have future applications.
REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION
Overview
Many of the current tools used to study the neurobiology of emotion are limited
in their ability to establish causal links among changes in regional brain func-
tion and mood. Repetitive transcranial magnetic stimulation (rTMS) holds
promise as a new paradigm to examine the nature of the neural systems regulat-
ing emotional processes and to identify their functional interrelations. The abil-
ity of rTMS to stimulate brain areas noninvasively is a significant advance be-
yond techniques that require the invasive method of direct cortical or transcranial
electrical stimulation. Evidence suggests that rTMS may have focal excitatory or
inhibitory cortical effects, offering the capacity to probe both the anatomical lo-
calization and the neurophysiological alterations that result in mood change. Re-
search with this new tool has contributed to our understanding of the neural
organization of emotion and has potential in the clinical treatment of mood
disorders.
Description of the Technique
Magnetic stimulators capitalize on the ability of time-varying magnetic fields to

induce eddy currents in biological tissue via the principle of electromagnetic in-
duction. The magnetic stimulator stores electrical current and then discharges it
in brief pulses through a stimulating coil. Each pulse produces a magnetic field
around the coil. When the resultant magnetic field is adjacent to a conducting
medium, such as nervous tissue, an electrical current is induced that results in
neuronal depolarization. This technique has been used to stimulate peripheral
nerves (Bickford & Fremming, 1965; Poison, Barker, & Freeston, 1982) and
more recently the central nervous system (Barker, 1985, 1987). Early magnetic
stimulators delivered single magnetic pulses at limited repetition rates ( 0.3 Hz),
referred to as single pulse TMS. Stimulation frequencies above 1 Hz available
with the new generation of stimulators are referred to as repetitive TMS.
Magnetic fields pass through scalp and skull without the impedance encoun-
tered by direct electrical stimulation, permitting enhanced control over the site
and intensity of stimulation. The focality of stimulation with rTMS depends on
coil design and orientation relative to neuronal fibers (Amassian et al., 1992; Co-
hen et al., 1990; Maccabee et al., 1993). The most focal coils have a resolution
of about 0.5 cm, as demonstrated in selective stimulation of the cortical repre-
sentation of neighboring muscle groups in the motor strip (Brasil-Neto et al.,
1992). The strength of the magnetic field falls off rapidly with increasing dis-
tance from the coil. Depth of stimulation, even at high intensity, is estimated to
be 2 cm below the scalp, reflecting stimulation of the underlying cortex near the
gray-white junction (Rudiak & Marg, 1994). This does not mean that rTMS does
not have remote or transsynaptic effects. For example, George et al. (1996) found
an increase in thyrotropin stimulating hormone following dorsolateral prefrontal
cortex (DPLFC) rTMS, suggesting subcortical effects. Acquiring 15O-PET dur-
ing rTMS, Paus et al. (1997) reported that rTMS to the frontal eye field resulted
in dose-dependent distal effects in superior parietal and medial parieto-occipital
regions, consistent with visual system connectivity.
Mood Effects in Normal Volunteers
There is preliminary evidence for regionally specific mood effects of rTMS in

normal subjects. Three studies found that rTMS of the left DLPFC transiently
induced dysphoria, whereas right DLPFC rTMS elevated mood in normal vol-
unteers (Dearing et al., 1996; George et al., 1996; Pascual-Leone, Catala, & Pas-
cual, 1996a). Dearing et al. (1996) found significant effects as early as 20 min-
utes post-stimulation, whereas George et al. (1996) found the peak mood change
at 5-8 hours. The mood changes in normal volunteers have been small in mag-
nitude and not well replicated. For example, in a recent study of 50 normal vol-
unteers receiving rTMS to the left DLPFC, Nedjat et al., (1998) reported three
cases of transient hypomania, highlighting the complexity of the topic but also
supporting potential mood-modulatory effects of rTMS.
Clinical Effects of Repetitive Transcranial Magnetic

Stimulation in Mood Disorders
Recent trials suggest that rTMS has therapeutic properties for major depression.
Four studies found that single pulse TMS reduces depressive symptoms (Gris-
aru et al., 1994; Hoflich et al., 1993; Kohbinger et al., 1995; Padberg et al., 1998).
Although left DLPFC rTMS is reported to induce transient sadness in normal
volunteers, recent studies show notable antidepressant effects when rTMS is de-
livered to the left DLPFC in depressed patients. Initial open-trial studies (Catala,
Rubio, & Pascual-Leone, 1996; George et al., 1995b) have been replicated in
two blinded, sham-controlled studies. Pascual-Leone et al. (1996b) reported that
5 days of left DLPFC rTMS had marked antidepressant effects in 11 of 17 med-
ication-resistant patients with psychotic depression. In another blinded, sham-
controlled, crossover trial, George et al. (1997) found that daily left DLPFC rTMS
had significant but modest antidepressant effects in outpatients with major de-
pression. The optimal laterality and frequency of stimulation are not presently
known. Evidence suggests that slow frequencies of rTMS (1 Hz) applied to the
right DLPFC may also be therapeutic (Klein et al., 1999).
The time course and laterality of rTMS-induced mood effects in patients and
normal volunteers differ. The mood effects of rTMS in normal volunteers have
been observed acutely following a single rTMS session, whereas therapeutic ben-
efit in patients with major depression has been reported following 1-2 weeks of
daily stimulation. The acute effects of a single rTMS session in 11 patients with
major depression has recently been examined. Left prefrontal rTMS appeared to
elevate mood acutely, whereas right-sided stimulation acutely worsened mood in
one case (B.D. Greenberg, personal communication, August 1997).
There is preliminary evidence that right but not left prefrontal rTMS may be
of benefit in mania (Grisaru et al., 1998), suggesting that the antimanic effects
show a laterality opposite to the antidepressant effect. Right DLPFC rTMS has
also been reported to improve mood in obsessive compulsive disorder (Green-
berg et al., 1997).
The Effects of Repetitive Transcranial Magnetic

Stimulation on Mood
The preliminary suggestions that slow TMS and rTMS have antidepressant prop-
erties have generated considerable interest in the clinical and research commu-
nities. The finding that rTMS may produce rapid antidepressant effects in se-
verely ill patients may result in the development of new treatment options. The
side-effect profile of nonconvulsive rTMS is more benign than that of ECT. To
date, the only major identified risk of rTMS is the possibility of seizure induc-
tion (Wassermann, 1998). Considerable work needs to be done, however, before
rTMS can be claimed to have clinical utility. For example, the evidence from the
initial studies suggests that the antidepressant effects are short-lived (Pascual-
Leone et al., 1996b). It is unknown whether more sustained effects can be
achieved by use of this intervention as a continuation treatment or in combina-
tion with antidepressant medications.
Regardless of ultimate clinical utility, the initial findings are striking in sug-
gesting that repetitive stimulation of a specific lateralized cortical area results in
antidepressant effects, whereas stimulation with similar parameters over the same
area in normal subjects transiently induces dysphoria. If confirmed, the inter-
pretation of this seeming paradox will be contingent on understanding of the lo-
cal and distal physiological effects of rTMS in illness and in health.
rTMS physiological effects demonstrate some degree of frequency depen-
dency, which has yielded new information about dynamic changes in the ex-
citability of motor pathways. For example, manipulations of frequency and in-
tensity produce distinct patterns of facilitation and inhibition of motor responses
with distinct time courses (Jennum, Winkel, & Fuglsang-Fredericksen, 1995;
Pascual-Leone et al., 1994; Wassermann et al., 1996). Ten minutes of 1 Hz rTMS
has been shown to inhibit corticospinal excitability, whereas higher frequencies
( 5 Hz) enhanced excitability for up to 30 minutes (Pascual-Leone & Tormos,
1997). These neurophysiological effects may relate to clinical applications of dif-
ferent rTMS frequencies. Frequency-dependent phenomena are seen in other ar-
eas (e.g., long-term potentiation and long-term depression in hippocampal slice
preparations) and result in differing physiological consequences. The possibility
of selectively producing post-stimulation excitation (disinhibition) or inhibition
in focal areas has remarkable potential for the mapping of brain-behavior rela-
tions and for developing targeted treatments.
The very preliminary evidence suggesting that both high frequency rTMS to the
left DLPFC and slow TMS to the right DLPFC have antidepressant properties raises
a new hypothesis regarding the role of lateralized neural systems in therapeutics,
at least in the context of rTMS. The hypothesis that high frequencies enhance ac-
tivity and low frequencies inhibit functional brain activity is far from proven.
Nonetheless, one may speculate that enhanced functional activity in left or sup-
pressed activity in right prefrontal areas may reduce depressive symptoms. Alter-
ing the lateralized balance of functional activity in a specific direction may be more
at issue than whether the particular intervention is inhibitory or excitatory.
Finally, the initial rTMS studies call for caution when generalizing from stud-
ies of therapeutics to discussions of the neural bases of normal variations in mood.
Stimulation with the same parameters over the same cortical site appears to have
differing effects on mood in normal and clinical samples. Key here will be the
determination of whether the physiological consequences of rTMS differ in de-
pressed and normal subjects or whether the mood effects are opposite in direc-
tion despite similar alterations of neurophysiology. The first possibility would
suggest that the neurophysiological disturbances accompanying the depressed
state provide a fundamentally different substrate for rTMS effects. The latter may
suggest intrinsic differences between depressed patients and healthy individuals
in neural systems that regulate mood.
CONCLUSIONS
By their nature, the various somatic treatments for mood disorders differ in their
likelihood of addressing anatomical or biochemical aspects of mood regulation.
Physical interventions, like ECT, neurosurgery, and rTMS, allow for experimental
manipulations that further understanding of the neuroanatomical bases of
therapeutic effects. The fact that the most recent antidepressant medications were
designed to target one or more chemical systems indicates a degree of neuro-
chemical specificity in this approach to therapeutics.
Across these interventions, it is now clear that there is anatomical and bio-
chemical specificity in how neural systems can be altered to suppress the symp-
toms of major depression and acute mania. It is also evident from much of this
work that therapeutic effects may be achieved by either intervention at different
nodes of a complex mood regulatory system or modulation of distinct networks.
Furthermore, while links may be sought between the mechanisms of action of
these therapeutic interventions and the pathophysiology of the disorders, the ne-
cessity of such linkage is not obvious. Effective treatments do not necessarily act
on or reverse the underlying pathological abnormalities (e.g., Nobler et al., 1994;
Sackeim et al., 1996). While the study of therapeutics is rich in offering hy-
potheses regarding the basic regulation of emotional processes, it is also evident
that caution is needed in generalizing from one arena to the other. The possibil-
ity that different neurophysiological alterations are associated with clinical dis-
orders and normal variation in mood and/or that patients with mood disorders
have distinct patterns of neural representation of affective processes requires se-
rious consideration.
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Index
AB (Aprosodia Battery), 84t, 88-89 heart rate and, 329, 331

Abulia impulsive-emotional, 320, 325
apathy and, 341 biological vs. psychological/
behavioral therapy for, 355 environmental factors, 334
Acoustical analysis, computerized, 89, 95 hormones, 332t
Activation, 397 neurobiological effects, 333
Activities of daily living (ADL), in post- neurochemistry, 332t
stroke depression, 248, 249/ neuropsychology, 331-333, 332t
Affect norepinephrine and, 326
definition of, 47 psychophysiology, 332t
disorders of. See Affective disorders stressful life events and, 333-334
expression of, 426 neurobiological influences, 321
flattening of, 436 neuropsychology, 321, 325
positive, 269-270 brain imaging studies, 323-324
positive vs. negative, 145 brain lesion studies, 323
states/traits, 139, 140f-141f tests, 322-323
Affective Auditory Verbal Learning Test, 97 psychophysiology
Affective deficits electroencephalogram, 330, 331
rehabilitation for, 426-427 heart rate and, 329, 331
Affective disorders. See also specific affective reactive, definition of, 322
disorders risk factors, 321-322
basal ganglia dysfunction and, 385 testosterone and, 326-327
in neurological conditions, 426 types
Age, changes with, 19, 91 affective/defensive vs. predatory,
Aggression 320-321
amygdala and, 219 neurobiological variables, 321
controlled-instrumental, 13, 320 reactive vs. proactive, 320-321
cortisol and, 327 validity of, 321
epilepsy and, 377 Agitations, 40, 41
493
494 INDEX
Agnosia, 47, 197 expression of, 424

Akinetic mutism, 344, 347, 352 frustration and, 180
Alcoholic violence, cortisol and, 327 stress reduction and, 424
Alexia, left hemisphere cortical dysfunction Anger behavior cycle, 425
and, 369 Angular gyrus, deficits, in violent behavior,
Alzheimer's disease 324
apathy in Anterior asymmetry, 12
decreased right temporal perfusion in, 345 Anterior capsulotomy, 473
methylphenidate for, 353-354 Anterior cingulotomy, 472-473
emotional deficits, 420 Antidepressants. See also specific
end-stage, amantadine for, 353 antidepressants
Amantadine, for apathy, 352-353, 354 for bipolar disorder, 457
Amnesia, 68 for depression, 457
Amphetamines, for apathy, 352 after traumatic brain injury, 261-262
Amygdala in schizophrenia, 443-444
ablation, 376, 393 mechanisms of action, 461-462
activation, 184 for mood disorders, 460-461
anatomy, 197 repetitive transcranial magnetic stimulation
atrophy, in Huntington's disease, 382 as, 124-125
consolidation effect and, 173 tricyclic. See Tricyclic antidepressants
cortices, 197 Antimanic agents, for mood disorders,
emotion-cognition connection and, 460-461
219-220 Antisocial behavior, temporal lobe deficits
lesions, 170, 197-198 and, 324
apathy and, 344 Anxiety
emotional communication and, 374—375 anxious apprehension, 12
facial expression recognition and, anxious arousal, 12
204-205 classification, 298
neural connections, 44, 63, 197 cognitive biases, 310-312
norepinephrine in, 170 cognitive impairments, 312-313
role, 197-198 cognitive studies, 310-313
in aggression, 219, 377 lesion studies, 308-310
in conditioning, 203-204 neuropsychological studies, 302-308,
in depression, 393 305t-307t
in development, 204 behavioral paradigms for, 306-308
in emotional experience, 198 electrophysiological paradigms for,
in encoding, 170, 183 303-306, 305f, 306f
in facial expression processing, 375 hemodynamic paradigms for, 303-306
in facial expression recognition, in Parkinson's disease, 380
198-200, 199/-201f, 202-203 prevalence, 298
in fear conditioning, 376 state vs. trait, 300-301
in learning, 170, 204 stress and, 301-302
in social judgment, 197-198 treatment
in secondary mania, 242 behavioral, 423
stimulation cognitive, 423
electrical, 218-219 relaxation, 423
rage and, 376 systematic desensitization, 423-424
visceral feedback hypothesis and, 388-390 types of, 299-301, 300t, 313
Amytal injection. See Wada test vs. panic, 62
Anagenesis, 48 Apathy
Anencephaly, 56 abulia and, 341
Anger in Alzheimer's disease, 345, 353-354
behavioral therapy for, 424-425 causes of, 342, 343t
cognitive therapy for, 424 dementia, 345
Index 495
localized brain dysfunction, 342-345 Assessment, emotional, 96-97. See also

psychiatric disorders, 345-346 Arousal; Emotional experience;
characteristics of, 340, 425 Expression; Perception
definitions of, 13, 340-342, 356 literature review, 81-82, 83t-85t, 86-93
diagnosis of, 425-426 neuroimaging
executive baseline for, 126-127
forms of, 348 statistical analysis for, 127
pharmacotherapy for, 352 study design for, 127
extreme. See Akinetic mutism test batteries and related studies, 83t-85t
social, 350 Association, reminiscence effect and,
states, conceptualizations of, 346-351 173
comparison of, 350-351 Attention
in disturbed arousal, 347 automatic capture, by emotion, 166-167
in frontal system dysfunction, 347-350 biases, in anxiety, 311
treatment, 351, 356 mediation of, 394
behavioral, 355-356 in schizophrenia, 441f
pharmacotherapy, 351-355 Atypical neuroleptics, for apathy, 352
rehabilitative, 355-356, 425-426 Augmentative and Alternative
Aphasia Communication systems, 426
depression in, 249-250 Automatic evaluation effect, 166-167
left hemisphere cortical dysfunction and, Autonomic arousal, 3, 4, 8, 89
368-369, 369 Avoidance behaviors, frontal lobe and,
Appraisals 398
components of, 165-166 Awareness, 46, 50
conscious/controlled, 168
current Background and general techniques, 4-7
bias content of emotional memories and, BAS (Behavioral Approach System), 269
179 Basal ganglia
missing information and, 179-181 in depression, 393
in depression, 169 diseases, 377, 399. See also Huntington's
dispositional attributions in, 169 disease; Parkinson's disease
fast/automatic, 166, 171 emotional communication in, 384
encoding and, 167-168 emotional experience in, 385
separate processing pathway for, 170 emotional perception in, 92
frontal lobe and, 170-171 progressive supranuclear palsy, 383
functions, 164 striatonigral degeneration, 384
of self-relevance, 165-166 Wilson's disease, 383-384
slow, 166 emotional expression and, 223
of stimulus, viewing time and, 167 lesions
Appraisal theory, 153-154 affective disorders and, 385
Apprehension, anxious, 299-301, 300t apathy from, 343-344, 350
Approach-avoidance, modular theory of Basic emotion models, 147-148
emotional expression and, 7-8, 396-398 Basotemporal cortex
Aprosodia Battery (AB), 84t, 88-89 lesions, mania and, 242
Aquinas, Thomas, 33 in secondary mania, 242
Aristotle, 33, 52, 142 Battery of Emotional Expression and
Arousal Comprehension (BEEC), 89-90
anxious, characteristics of, 300-301, 300t Beck Depression Inventory, 81, 380
assessment tools for, 89 BEEC (Battery of Emotional Expression and
control, hemispheric asymmetrical, 8, 396 Comprehension), 89-90
disturbed, apathy in, 347 Behavior, emotional, 398
modular theory of emotional expression Behavioral Approach System (BAS), 269
and, 394-396 Behavioral Inhibition System (BIS), 269
peripheral autonomic, assessment of, 396 Behavioral studies, of anxiety, 306-308
496 INDEX
Behavioral therapy regional function studies, inconsistencies

for anger, 424-425 in, 298-299
for anxiety, 423 structure
for apathy, 355-356 abnormal, vs. dysfunction, 109-110
for depression, 422-423 computed tomography, 112
for post-traumatic stress disorder, 423 subcortical. See Subcortical structures
stategies, 422-423 Brain lesion method, 3, 5
Between-group analysis, 107 Brain stem
Biases, cognitive, in anxiety, 310-312 circuitry, 57-58
Biology vs. culture debate, 143 integrative mechanisms, in emotional
Bipolar disorder processing, 61-62
after stroke pontine, 56
diagnosis of, 245-246 pontine level, 56
lesion location in, 245, 246t subsystems, in emotional processing,
cerebral glucose metabolism in, 283-286, 60-61
285f 286f Brief Psychiatric Rating Scale, 96
mania, 10 Broca's aphasia, 226
pharmacotherapy, 383 Bromocriptine
BIS (Behavioral Inhibition System), 269 for akinetic mutism, 352
Blood flow, regional cerebral. See Regional for apathy, 353
cerebral blood flow Buck slides, 94
Blood oxygen level-dependent functional
magnetic resonance imaging (BOLD), Capgras syndrome, 350
119-120 Capsulotomy, anterior, 473
Bodily processes, 47 Caregiver participation, in rehabilitation,
BOLD (blood oxygen level-dependent 416
functional magnetic resonance Cartesian impasse, 33, 40, 41, 52
imaging), 119-120 Catastrophic reaction, 239-240
Brain. See also specific brain structures Category error, 40
in anxiety vs. depression, 305-306 Caudality
basal lateral circuits, 376 anterior vs. posterior brain structures, 4
blood flow. See Regional cerebral blood Center-Periphery debate, 143-144
flow Central details, 167, 168
dysfunction, vs. structural abnormality, Cerebellar diaschisis, 112
109-110 Cerebral blood flow. See Regional cerebral
hemispheres. See also Left hemisphere; blood flow
Right hemisphere Cerebral cortex dysfunction, 399
anterior/posterior dimensions in, 272 Cerebral glucose metabolism. See Glucose
asymmetry of. See Hemispheric metabolism, cerebral
asymmetry Cerebral inactivation, 271-273
laterality of. See Laterality Cerebral metabolism, methodological issues,
imaging studies. See also specific imaging 278-279
methods Cerebrospinal fluid (CSF)
in aggression, 323-324 norepinephrine, in antisocial behavior,
of ECT efficacy, 469-470 325-326
injury serotonin, in antisocial behavior, 325-326
evaluation of emotional experience in, volumes, in depression with schizophrenia,
91 445-446, 446f
traumatic. See Traumatic brain injury Cerebrovascular disease, 11
lesions, aggression and, 323 Channels of emotional communication
localized dysfunction, apathy and, 342-345 facial, 4, 81, 95, 426
metabolism, positron emission tomography general, 4, 90, 95, 426, 427
of, 118 gestural, 4, 81, 95
processing levels, 42-43, 56 lexical/verbal, 4, 81, 95, 426
Index 497
postural, 4, 81 deficits
prosodic/intonational, 4, 81, 95, 426 in left hemisphere cortical dysfunction,
quantification of features, 95 368-369
scenic, 6, 81 in right hemisphere cortical dysfunction,
Chimeric Faces Task (CFT), 307-308 370-372
Chorea, Huntington's, 382-383 disorders, mechanisms of, 385-387
Cingulate gyms, 215-216, 349 in Huntington's disease, 382
Cingulotomy, anterior, 472-473 limbic system dysfunction and, 374-375
Circuit models, 146-147 in Parkinson's disease, 378-380
Citalopram, for post-stroke depression, Compensation training, 415
253-254 Componential approach to emotional
Clinical implications, 3-4, 14-17 processing, 4, 6, 10, 16, 81, 82, 90,
Clonidine, for secondary mania, 244 427
Clozaril, for schizophrenia negative Componential models
symptoms, 444 profile of, 15If
Cognition synthesis with other models, 150-152
affective, 47-48, 49f, 50 types of, 149-150
in anxiety, 310-313 Comprehension
brain processing disorders, in right hemisphere cortical
levels of, 42-43 dysfunction, 370-371
speed of, 43-44 left hemisphere cortical dysfunction and,
corticolimbic mechanisms of, 66-68 368-369
definition of, 46 Computed tomography (CT), 112
domains. See Emotion Computerized Speech Laboratory, 95
impairments, in anxiety, 312-313 Conditioning, amygdala role in, 203-204
motivation and, 45 Consciousness, 51-52
philosophical conceptualizations, 33-42 Convulsive therapy. See Electroconvulsive
rational, 47-48, 49f, 50 therapy
syncretic vs. analytic, 47-48 Corpus callosum deficits, in violent behavior,
vs. emotion, 42, 97-98 324
Cognition-emotion debate, 142 Cortical/subcortical, 4
Cognition system, vs. emotional system, Cortical systems
220-221, 222t anatomy/physiology of, 65-69
Cognitive functions, emotional stimuli and, dysfunction, and emotional deficits
97-98 left hemisphere, 368-370
Cognitive knowledge, 42 right hemisphere, 370-374
Cognitive psychology, memory and, in post-stroke mood disorders, 252
165 Corticobulbar dysfunction, 374
Cognitive rehabilitation, 414-416 Corticolimbic evolution, archicortical/
functional skills training, 414 paleocortical routes of, 65-66
process approach, 414—416 Cortisol, violence and, 327
Cognitive systems, emotional systems and, Crying, pathological, 240
218-220 CSF. See Cerebrospinal fluid
Cognitive therapy CT (computed tomography), 112
for anger, 424 Cues
for anxiety, 423 affective, bias from, 174-175
for depression, 422 for retrieval process, 174
for post-traumatic stress disorder, 423 Cultural issues, 21
principles, 422
Cognizance, 50 Dacrystic epilepsy, emotional changes in, 377
Communication, emotional Darwin, Charles, 143, 147
in basal ganglia diseases, 384 Darwinists, 34
channels of. See Channels of emotional Dementia. See also Alzheimer's disease
communication apathy in, 345
498 INDEX
Depression Diaschisis, 242

akinetic, 437 Dichotic listening, 5
apathy in, 345-346 Diencephalic theories, of emotional
appraisals in, 169 expression, 390-391
after brain injury. See Traumatic brain Diencephalon, 57. See also Hypothalamus;
injury, depression after Thalamus
with comprehension deficits, diagnosis of, Differential Emotions Scale, 96
248-249 Dimensional emotion models
delusional vs. nondelusional, 457 modular theory and, 391
in elderly, 276 multidimensional, 145-146
emotional expression and perception, 93 profile of, 15If
after functional neurosurgery, 472 synthesis with other models, 150-152
internal expression assessment in, 96 unidimensional, 145
left frontal activity and, 270 vs. discrete model, 4, 7
melancholic vs. severe, 457-458 Discourse production, 17, 371
negative ruminative self-evaluation and, Discrete emotion models
172 description of, 146-148
neurobiology profile of, 15If
electroencephalogram studies, 273-277 synthesis with other models, 150-152
evoked potential studies, 277-278 vs. dimensional model, 4
glucose metabolism in, 283-286, 285f Dopamine reduction, in Parkinson-associated
286f depression, 381
physiologic brain changes, 393 Dopaminergic drugs, for apathy, 352,
regional abnormalities, 286-288 353-354
regional cerebral blood flow, 281-283 Dorsal circuit, 67
in Parkinson's disease. See Parkinson's Dorsolateral prefrontal circuit, in apathy,
disease, depression in 348-349
pharmacogenic, 436-437 Dorsomedial thalamic nucleus, damage,
postpsychotic, 435 apathy and, 344
sadness and, 180 Drives
scales for evaluating, 96 definition of, 48
in schizophrenia. See Schizophrenia, limbic mechanisms, 71-73
depression in Drugs. See also specific drugs or classes of
self-concept and, 175-176 drugs
after stroke. See Stroke, depression after memory-impairing, 170
after traumatic brain injury. See Traumatic Dualism, 33-34
brain injury, depression after Dysphoria, in Parkinson's disease, 381
treatment, 422
behavioral interventions for, 422-423 Ecological realism, 46
cognitive therapy for, 422 Ecological validity, 97
electroconvulsive, 462 Ecphoric process, 174-175
repetitive transcranial magnetic ECT. See Electroconvulsive therapy
stimulation for, 476-478 EEG. See Electroencephalography
vegetative symptoms, 435 Elation, 11,240-242
Descartes, Rene, 33, 142-143 Elderly depression, EEG patterns in, 276
Development, amygdala role in, 204 Electroconvulsive therapy (ECT)
Developmental-evolutionary perspective, 5 anticonvulsant effects, 466-468
Dewey, John, 36, 37 bilateral seizure generation in, 465-466
Dextroamphetamine, for post-TBI depression, efficacy
262 in deep subcortical structures, 466
Diagnostic and Statistical Manual of Mental generalized vs. localized effects,
Disorders (DSM-III-R), 245 463-464
Diagnostic and Statistical Manual of Mental lateralization in emotional regulation
Disorders (DSM-IV), 298 and, 468-471
Index 499
of low dosage right unilateral method, influence

465-468 on memory, 164, 165, 184-185
in prefrontal cortex, 468 on subjective experience of
technical factors and, 464-465 remembering, 181-182
historical aspects, 456, 462-463 information
indications, 462 postevent elaboration/consolidation of,
left unilateral, 463, 469 172-174
for mood disorder, 458 retrieval, neural mechanisms in,
for post-TBI depression, 262 182-184
right unilateral knowledge of, 42, 196-197. See also
low dosage, inefficacy of, 465-468 Appraisals
nonverbal memory deficits after, 469 environmental factors and, 208-209
vs. left unilateral, 463 neural structures in, 208
Electroencephalography (EEG) somatosensory cortices and, 205-206,
aggression/violence, 330, 331 207f, 208
in anxiety, 304-305, 305f 306f memory and, hierarchic anatomy of, 70-71
of depression, 274-277 motivation and, 45
of induced sadness, 274 negative, right hemisphere and, 217
methodological issues, 273-274 neuroimaging. See Neuroimaging of emotion
quantitative, 112, 113t, 114 neuropsychological theories. See
Elicitation of emotional expression Neuropsychological theories
procedures for, 94 perception, tests of, 97
research on, 153-154 philosophical conceptualizations, 33-42
Eliminative materialists, 111 positive, 7, 20, 21
Emotion psychological functions and, 155-156
automatic capture of attention by, 166-167 psychological models. See also
brain processing system. See Emotional Dimensional emotion models;
processing systems Discrete emotion models
cerebral hemispheric specialization current, description of, 144-150
theories, evidence for, 3-4 historical aspects of, 142-144
communication. See Communication, recognition, in schizophrenia, 441-442, 442f
emotional recollective experience and, 182
continuum, terminology for, 145 regulation, by pharmacologic agents,
control, descending projections for, 460-461
68-69 rehabilitation, 4—14
current, evaluations of past episodes and, retrieval process and, 174-184
175-182 social, 20, 21
definition of, 3, 18, 80, 138-139 somatic changes from, 195
delimitation of, 139, 140f-141f, 142 subcortical bases, 60-64, 69-70, 215-216
descriptions of, 367 subjective experience of. See Affect
differentiation subject matter of, 195
endogenous viewpoint, 153-154 survival value of, 195
exogenous viewpoint, 153 systems-level theory, 195
dimensions and emotion type, 7 theoretical models, 21
dimensions vs. discrete emotions, 10 treatment of, 418-427
domains, 139, 398. See also Emotional valence, 7
experience vs. cognition, 10, 42, 97-98, 142
episodic nature of, 137-138 vs. feelings, 139, 143
expression of. See Expression withdrawal-related, frontal asymmetry and,
function of, 20 8, 270-271
global neural processing mode changes Emotional disorders, 11-14. See also specific
and, 195 emotional disorders
guidance of encoding, 165-172 with brain damage, historical aspects of,
historical aspects of, 31 239-240
500 INDEX
Emotional disorders (continued) multiple, via multiple channels, 84t-85t,

with common neurological disorders, 89-93
419-421 multiple, via single channel, 84t, 88-89
treatment of, 418-421 single, via multiple channels, 82,
Emotional experience. See also Affect 83t-84t, 86-88
appraisals. See Appraisals somatosensory cortices and, 205-206,
assessment tools for 207f 208
New York Emotion Battery, 90-91 speed of, 43-44
related studies, 89, 91 neural mechanisms/substrates, 3, 18
brain disorders and, 367-368 neurological assessment. See Assessment,
constructive processes in, 164 emotional
defects, 399 neuropsychological studies
duration of, 180, 367 background, 4-7
evaluation of subjective experience, 91, brain organization and, 4
95-96 general techniques, 4-7
extended, memory for, 180 parameters of, 4
left hemisphere cortical dysfunction and, processing modes, 4, 427
370 vs. cognition system, 220-221, 222t
limbic system dysfunction and, 375-377 Emotional situations/scenes, assessment of,
mechanisms, 387 84t, 89
central theories, 390-398 Emotional states, 138
feedback theories, 387-390 Emotional Stroop Task, 97
mediation, limbic circuits and, 368 Emotive knowledge, 32
negative Empiricism, 33-34
recall of, 176 Encephalitis, limbic, 376
rehearsal of, 172 Encephalization, 57, 59
positive, recall of, 176 Encoding
in psychological disorders. See under amygdala and, 183
specific psychological disorders amygdala function in, 170
recreating, importance of, 163-164 duration of emotional events, 180
in right hemisphere cortical dysfunction, 372 frontal lobe and, 170-171
self-defining, control over, 178 guidance, by emotion, 165-172
significance, reevaluation of, 178-179 of memories, 164-165
theories, 399-400 neural mechanisms of, 169-171
Emotional incontinence, 240 schema-guided, 168-169
Emotional labililty, 240 vividness of memory and, 181-182
Emotional memory system English neorealism, 37-38
deficits, neuropsychological mechanisms Environmental factors, knowledge of emotion
of, 373 and, 208-209
implicit, 44 Epilepsy
in right hemisphere cortical dysfunction, aggression and, 377
372-373 aggression in, 219
Emotional processing systems mood disturbances in, 271
cognitive systems and, 218-220 violence and, 323
common language, need for, 21 Epinephrine, 389
componential nature of, 221-224, 222f. Epistemics, 32
See also Componential approach to Epistemology, 32
emotional processing Event-related potentials (ERPs)
hierarchical organization of, 224-227, 427 in aggression/violence, 330, 331
lateralization of, 206 in anxiety, 304
levels of, 42-43 Evoked potentials
modalities, 4 depression studies, 277-278
modes. See also Arousal; Emotional methodological issues, 277
experience; Expression; Perception Experimental affect battery, 93
Index 501
Experimental studies, 3 facial expression, impaired recognition of,

Expression 198, 201f
assessment tools for, 88-93 Feedback theories, of emotional expression,
Aprosodia Battery, 88-89 387-390
Battery of Emotional Expression and Feelings. See also Affect;
Comprehension, 89-90 Emotional experience
experimental affect battery, 93 knowledge-by-acquaintance, 46
New York Emotion Battery, 90-91 subjective, 95-96, 155
related studies, 88, 91-93 vs. emotions, 40, 139, 143
deficits, in right cortical dysfunction, Flattening of affect, 436
371-372 Florida Affect Battery (FAB), 87
elicitation. See Elicitation of emotional Fluency tests, 98
expression Fluvoxamine, for schizophrenia negative
evaluation procedures, 94-96 symptoms, 444-445
external, observations of, 94-95 fMRI. See Functional magnetic resonance
facial. See Facial expression imaging
left hemisphere cortical dysfunction and, Formalization, of language, 44-45
369 Friedes Neuropsychological Personality
literature on, 83t-84t, 88 Survey, 96
rating procedures for, 90-91 Frontal leukotomy, 471
in schizophrenia, 434-436 Frontal lobe
subcortical structures and, 91-92, 215-216 affective appraisals and, 170-171
The Expression of Emotion in Man and asymmetry, withdrawal-related emotions
Animals (Darwin), 143, 147 and, 270
attentional-arousal systems and, 395
FAB (Florida Affect Battery), 87 avoidance behaviors and, 398
Facial Action Coding System (FACS), 92, 95 bilateral cortical dysfunction, 373-374
Facial asymmetry, 5 dementia, apathy in, 345
Facial expression dorsolateral, 397
deficits glucose metabolism, violent behavior and,
frontal lobe damage and, 224 324
in Parkinson's disease, 378-379 intentional control of emotion and, 223-224
in right hemisphere cortical dysfunction, left, inactivation, depression and, 272
371 lesions
in schizophrenia, 434—436 aggression and, 323-324
in stroke, 223 apathy and, 342-343, 347-350, 355
discrimination defects, right hemisphere episodic memory retrieval and, 183
damage and, 386 facial emotional expressions and, 224
of fear, amygdala and, 375 manual grasp response and, 398
knowledge of emotion and, 196 memory deficits in, 73-74
processing Frontal lobe syndrome, 323, 325
in Huntington's disease, 382 Frontotemporal lobar dysfunction, apathy in,
somatosensory cortices and, 205-206, 345
207f 208 Frustration, anger and, 180
recognition Functional communication, 97
amygdala and, 198-200, 199/-201f Functional imaging
202-203 of blood flow and energy metabolism, 110
amygdala damage and, 204-205 brain structural abnormality, vs.
in schizophrenia, 441-442, 442f dysfunction, 109-110
unilateral facial manipulation, 94 information from multiple conceptual
Facial feedback hypothesis, 387-388 levels, 109
"Faculty" doctrines, 142 interpretation of, 110-111
Fear paradigms, 106-109
conditioning, amygdala and, 63, 203-204 problems, common, 125-127
502 INDEX
Functional imaging (continued) Hemispheres

techniques, 22, 112, 127. See specific interhemispheric, 4
functional imaging techniques intrahemispheric, 4
with transcranial magnetic stimulation, Hemispheric asymmetry
125, 126f in anxiety, 304-305, 305f 306f
Functionalists, 111 arousal control and, 5, 396
Functional magnetic resonance imaging in depression, EEG studies of, 275-277
(fMRI) in emotional expression, 226-227
blood oxygen level-dependent, 119-120 cortical structures and, 227-229
inversion recovery, 119 subcortical structures and, 227-229
serial perfusion technique, 120-121, in emotional representation, 7, 216-218,
121f 219
serial perfusion, 120-121, 121f prosodic, 370
spin labeling, 119, 120 in regional cerebral blood flow, in induced
vs. other imaging methods, 112, 113t mood states, 279-281
Functional neurosurgery right-hemispheric specialization for
definition of, 471 emotion, theoretical basis for, 7
historical aspects, 471-72 valence, pharmacotherapy and, 393-394
in mood disorders, 473-474 Hemispheric valence hypothesis, 7, 393
postsurgical affective symptoms, 472 Herpes simplex infection, emotional changes
stereotactic procedures for, 472-473 in, 376
Functional skills training, 414 5-HIAA. See Serotonin
Hierarchic integration, Jacksonian, 57, 58
GAD (generalized anxiety disorder), 301, 303 Hippocampus
Gelastic seizures, 20 anticipatory functions, 63, 64
Gender differences, 19-20, 117-118, 117f in emotional expression, 215-216
Generalization of treatment, 418 memory and, 182, 183
Generalized anxiety disorder (GAD), 301, HMPAO, 114
303 Hormones, violence and, 326-328
Geriatric Depression Screening Scale, 96 Huntington's disease
Gestures, in right hemisphere cortical emotional communication in, 382
dysfunction, 371 emotional experience in, 382-383
"Ghost in the machine," 48, 49f 50 Hypoglycemia, violence and, 327-328
Gibson, James J., 46 Hypothalamus
Glucogen, violence and, 328 in autonomic components of emotion,
Glucose metabolism, cerebral 223
in depression in emotion, 220
bipolar vs. unipolar, 283-286, 285f, 286f in emotional expression, 215-216
with schizophrenia, 445, 446-447, 447f emotional expression and, 390-391
electroconvulsive therapy and, 467 functions, 62, 197
in Huntington's disease, 383 ventromedial, 62
Grieving process, for depression after brain
injury, 423 LAPS (International Affective Picture
Guilt, shame and, 180 System), 94
Inclinations, 40
Haloperidol, for schizophrenia negative Indifference, treatment of, 425-426
symptoms, 444 Indifference reaction, 240. See also Apathy
Halstead-Reitan Neuropsychological Test Individual differences, 19-20
Battery, 322 Inflammatory disease, emotional changes in,
Hamilton Depression Rating Scale scores 376
in post-stroke depression, 253-254, 254f Instincts, 48
in schizophrenia, 436 Insulin, violence and, 327-328
Heart rate, violence and, 329, 331 Interceptors, 46-47
Hemiparkinson's disease, 92-93, 380-381 Interhemispheric factor, 4. See Laterality
Index 503
Interictal phenomenon, emotional changes in, Levodopa, for depression in Parkinson's

376-377 disease, 381
International Affective Picture System Lexical models, 148
(LAPS), 94 Lexical/verbal emotion, 4. See also Channels
Interrater reliability, 95 of emotional communication
Intrahemispheric factor, 4 Limbic system
back projections, 72-73
Jacksonian hierarchic integration, 57, 58 drive mechanisms, 71-73
James, William, 34, 35-36, 37, 143-144 dysfunction, 399
James-Lange theory, 139 emotional communication and, 374-375
Kltiver-Bucy syndrome, 344 emotional experience and, 375-377
Knowledge emotional functions of, 216
of emotion, 196-197 forward projections, 72-73
hierarchy, 50 mechanisms of, 70
levels of, 50-52 structures. See also Amygdala;
Knowledge-by-acquaintance, 46, 48, 50 Hippocampus
Knowledge-by-description, 46, 48, 50 anticipatory, 63-64
integrative influences on emotion and
Labeling, of emotional states, 148 cognition, 61-62
Language surgical ablation of, affective symptoms
formalization of, 44—45, 52 after, 471
left hemisphere cortical dysfunction and, "Logical atoms," 38
368-369 Luria-Nebraska Neuropsychological Battery,
ordinary, analysis of, 39-42 322
role of, 50-51
"Language games," 39—40 Magnetic resonance imaging (MRI)
Laterality. See also Hemispheric asymmetry of amygdala damage, 198, 199f
definition of, 4 BOLD technique, 108
electroconvulsive therapy efficacy and, conventional, 112
468-471 functional. See Functional magnetic
experimental behavioral techniques, 5 resonance imaging
in parkinsonian motor symptoms, 92-93, within-individual analysis, 108
380-381 Magnetic resonance spectroscopy (MRS),
Lateralization, in emotional regulation, 4, 121-122
468-471 Mania
Laughing, pathological, 240 bipolar disorder, and, 11
Learning, amygdala role in, 170, 204 electroconvulsive therapy for, 462
LeDoux resolution, of Zajonc-Lazarus debate, in schizophrenia, 439-441
43-44 after stroke. See Stroke, mania after
Left hemisphere after traumatic brain injury. See Traumatic
cortical dysfunction, 368-370 brain injury, mania after
deficits Maximally Discriminative Facial Movement
in aggression, 323 Coding System, 95
in violent behavior, 324 Meaning, pragmatic theory of, 35
emotion production and, 217, 269 Meaning oriented models
lesions description of, 148-149, 15 1t
anxiety and, 308-310 synthesis with other models, 150-152
catastrophic-depressive reaction, 392 Melodic Intonation Therapy, 415
emotional communication and, 386 Memory
emotional disorders in, 240 of action vs. appearance, 168
emotional expression and, 183 of central details, 168
emotional reactivity in, 226-227 circuits, 67
with stroke-related depression, 248 construction process, emotion and,
unilateral neglect syndrome and, 228-229 175-176
504 INDEX
Memory (continued) repetitive transcranial magnetic stimulation

corticolimbic mechanisms of, 66-68 effects on normal volunteers, 475-476
declarative or explicit, 44 in right hemisphere cortical dysfunction, 372
deficits, in frontal lobe lesions, 73-74 vs. emotion, 47
distortions/biases, 165 Mood and Anxiety Symptom Questionnaire,
emotional, current appraisals and, 179 305, 307f
emotional influences on, 164, 165, Mood disorders
184-185 bipolar. See Bipolar disorder
field perspective, 181 with brain injury, 262-263
improved, viewing time and, 167 mania. See Mania
norepinephrine and, 170 neurobiology of, 459-460
observer perspective, 181 pathophysiology of, 458, 461-462
of peripheral details, 168 phases of, 458-460
reference/procedural or associative, 64 post-stroke, cortical vs. subcortical lesions
rehearsal and, 172-173 in, 252
reminiscence effect and, 173 psychiatric populations, 17
retrograde deficits, in right hemisphere psychopharmacology
cortical dysfunction, 372-373 mechanisms of action, 461-462
of schema-relevant information, 168 neurobiological studies of, 459
usefulness of, 163-164 repetitive transcranial magnetic stimulation
vividness, 181-182 for, 476-478
working/declarative or configural, 64 treatment interventions, 478
Mesencephalic reticular formation (MRF), unipolar. See Depression
395-396 Mood induction procedures, 94, 98
Mesencephalon, 57 Motivation
Methylphenidate definition of, 45-46
for apathy, 353-354 emotion, cognition and, 45
for post-TBI depression, 262 intrinsic, 74-75
Mind-body debate, 142-143 ventral medial frontal and orbital frontal
Minnesota Multiphasic Inventory (MMPI), cortices, 171
81, 392 Motivational-emotional system, 45-46
MMPI-2, 95 Motive persistence, 73-74
Modal emotions, 149-150 Motor activation, modular theory of
Modular theory of emotional expression, emotional expression and, 15,
391-398 396-398
approach-avoidance and, 396-398 Motor direction, 7
approach and withdrawal, 7-8 MRF (mesencephalic reticular formation),
arousal and, 8, 394-396 395-396
motor activation and, 396-398 MRI. See Magnetic resonance imaging
motor direction, 7-8 MRS (magnetic resonance spectroscopy),
valence and, 7, 391-394 121-122
Monism, 33-34 Multidisciplinary approach to rehabilitation,
Monoamine oxidase inhibitors 15, 416
for bipolar disorder, 457 Multiple sclerosis, emotional deficits,
for depression, 457 420-421
for Parkinson-associated depression, 381 Murderers, brain imaging studies, 324
Mood Mutism
as emotional component, 40 akinetic, 344, 347, 352
laterality in parkinsonian motor symptoms model of, 351
and, 380-381
left hemisphere cortical dysfunction and, Naturalistic observation approach, 88
370 Negative affect, 269-270
regulation, retrieval and, 177-179 Neglect of the left half of space, 240
Index 505
Neocortical, 4 Neurosurgery, functional. See Functional

Neural mechanisms neurosurgery
in emotional information retrieval, 182-184 Neurotransmitters, in apathy, 352
in emotional processing, 3, 81 New York Emotion Battery (NYEB), 90-91
Neurobehavioral Rating Scale, 96 Noetic approach, for cognitive rehabilitation,
Neuroanatomy, evolutionary, 57-59 415-416
Neurobiological studies. See under specific Norepinephrine
disorders cerebrospinal fluid levels, in antisocial
Neurobiological systems-level theory of behavior, 325-326
emotion, 9-10 memory and, 170
Neurochemistry, of violence, 325-326 in Parkinson's disease, 381
Neuroimaging of emotion, 106 Normative data, 81-93
baseline for, 126-127 Nortriptyline, for post-stroke depression, 253,
functional. See Functional imaging 254f
statistical analysis for, 127 Nucleus basalis, 70
study design for, 127 NYEB (New York Emotion Battery), 90-91
techniques, common problems of, 125-127
Neuroleptics Observation
for apathy, 354 of external expression, 94-95
atypical, for depression treatment, in of internal states and dispositions, 95-96
schizophrenia, 444 Obsessive-compulsive disorder (OCD)
Neurological epistemology, 32 anxious apprehension in, 301
Neuromotor programs, 147 with depression, rCBF in, 303
Neuropharmacology, of Parkinson's disease, Occupational therapist, role on rehabilitation
381-382 team, 4l7t
Neuropsychological tests Olanzapine, for schizophrenia negative
for aggression, 322-323 symptoms, 444
compendium of, 80, 81-93 Orbitofrontal cortex
for emotional processing, 81-93 lesions
Neuropsychological theories of emotion, 7-11 mania and, 242
current, 218-229, 222f. See also Cognitive motivational deficits and, 171
systems; Emotional processing systems in secondary mania, 242-243
componential nature of emotional Orbitofrontal lobotomy, 349
processing system, 221-224, 222t. See
also Componential approach to PAG (periaqueductal gray), 61
emotional processing Pain
distinction between emotional and cues, retrieval bias from, 175
cognition systems, 220-221, 222t past, memories of, 177-178
hierarchical organization of emotional PANAS model, 145
system, 224-227 Panic
left/right and cortical/subcortical regional cerebral blood flow in, 303-304
dichotomies in emotion and, 4, 227-229 survival value of, 298
relationship of emotional and cognition vs. anxiety, 62
systems, 97-98, 218-220 Parameters of emotional processing, 4
historical development, 214-218 Parkinson's disease (PD)
Neuropsychologist, role on rehabilitation depression in, 254-255, 262, 380
team, 417t diagnosis of, 380
Neuroscientists mechanism of, 257-258
compendium of, 80, 81-93 prevalence of, 255, 255f
eliminative materialists, 111 relationship to cognitive impairment,
for emotional processing, 81-93 256-257, 256f
functionalists, 111 treatment of, 258
reductive materialists, 111 emotional communication in, 378-380
506 INDEX
Parkinson's disease (PD) (continued) Positron emission tomography (PET)

emotional deficits, 420 blood flow studies, 116-118, 117f
emotional experience in, 380-382 brain metabolism studies, 118
emotional expression and perception in, coincidence detection, 116
92-93, 223 vs. other imaging methods, 112, 113t
neuropharmacology, 381-382 vs. SPECT, 116
unilateral hemispheric pathology in, 92-93 Post-Stroke Depression Rating Scale, 96
Pathological emotionalism, 240 Post-traumatic stress disorder
Pathological laughing or crying, 240 behavioral therapy for, 423
PD. See Parkinson's disease cognitive therapy for, 423
Peirce, C.S., 35 relaxation training for, 423
Pemoline, for post-TBI depression, 262 systematic desensitization for, 423-424
Perception Pragmatics, 17, 96, 417, 426
assessment tools for, 87-88 Pragmatism, 34-37
Aprosodia Battery, 88-89 Pragnosia, 96
Battery of Emotional Expression and Prefrontal cortex
Comprehension, 89-90 in depression, 393
experimental affect battery, 93 functional activity, electroconvulsive
New York Emotion Battery, 90-91 therapy and, 468
Perception of Emotions Test, 86 Primary affects, 47, 48
Profile of Nonverbal Sensitivity, 82, 86 Primes, 46, 48
related studies, 87, 88, 91-93 Process approach, for cognitive rehabilitation,
Victoria Emotion Perception Test, 86 414-416
disorders, in right hemisphere cortical Processing modes, 4, 81-82
dysfunction, 370-371 Profile of Nonverbal Sensitivity (PONS), 82,
emotional, 4, 81 86
motivated, physiology of, 72-73 Progressive supranuclear palsy (PSP), 383
right hemisphere and, 269 Prosody
subcortical lesion effects on, 91-92 assessment tools for
Perception of Emotions Test (POET), 86 Aprosodia Battery, 88-89
Periaqueductal gray (PAG), 61 Battery of Emotional Expression and
Peripheral autonomic arousal, assessment, 3% Comprehension, 89-90
Peripheral details, 167, 168 experimental affect battery, 93
Perisylvian lesions, catastrophic-depressive Florida Affect Battery, 87
reaction in, 392 New York Emotion Battery, 90-91
Personality Assessment Inventory, 95 Perception of Emotions Test, 86
PET. See Positron emission tomography Profile of Nonverbal Sensitivity, 82. 83
Pharmacotherapy. See also specific related studies, 87, 91-93
pharmacotherapeutic agents Victoria Emotion Perception Test, 86
for mood disorders. See under specific emotional
mood disorders left hemisphere damage and, 386
for regulation of emotion, 460-461 right hemisphere damage and, 386-387
Physiatrist, role on rehabilitation team, 417t in Parkinson's disease, 92-93, 379-380
Physical abuse, impulsive-emotional positron emission tomography of, 118
aggression and, 333-334 Pseudobulbar affect, 240
Physical therapist, role on rehabilitation team, PSP (progressive supranuclear palsy), 383
417t Psychiatric disorders, apathy in, 345-346
Plato, 33, 142 Psychiatrist, role on rehabilitation team, 417t
POET (Perception of Emotions Test), 86 Psychic akinesia, 343-344
PONS (Profile of Nonverbal Sensitivity), 82, Psychological functions, emotional effects on,
86 155-156
Portland Adaptability Inventory, 96 Psychological models of emotion, 144, 156
Positive emotions, 20, 21 componential, 149-150
Positivism, 37-39, 41-42 dimensional, 145-146
Index 507
discrete, 146-148 for apathy, 355-356

meaning oriented, 148-149 assessment techniques, 416-417
research foci, current, 153-156 caregiver participation in, 416
synthesis of, 150-152 cognitive, approaches for, 414-416
Psychometrics, 21-22, 82, 97 cognitive remediation, 414
Psychomotor seizures, emotional changes in, communication abilities, 417
376-377 for emotional deficits, 427
Psychopharmacological treatment, of generalization strategies for, 418
emotional disorders, 421 multidisciplinary treatment, 15, 416, 417t
Psychopharmacological treatments, in mood process approach to, 414
disorders, 457-462 team, professional roles in, 416, 41 7t
Psychosis, schizo-affective, 438 Rehearsal, of emotional information, 172-173
Psychostimulants, for post-TBI depression, Relative judgment theory, 351
262 Relaxation training, 423
Psychosurgery. See Functional neurosurgery Relevance detectors, 138
Psychotherapist, role on rehabilitation team, Remediation. See Rehabilitation
417t Remembering, subjectivity of, 181-182
Remember/know procedure, 182
Quantification of features in evaluation of Reminiscence effect, 173
emotion Repetitive transcranial magnetic stimulation
computerized voice analysis, 95 (rTMS), 470, 474. See also TMS
discourse analysis, 95 clinical effects in mood disorders,
facial muscle action units, 95 476-478
description of, 475
Rabies, emotional changes in, 376 mood effects, on normal volunteers,
Radical empiricism, metaphysics of, 35 475-476, 476-478
Rating procedures for emotional expression, Research
94-95 future directions for, 18-21
Rationalism, 33-34 research considerations, 18-21
rCBF. See Regional cerebral blood flow Reserpine
Reaction modalities, patterning of, 154—155 for dysphoria in Parkinson's disease, 381
"Reaction triad" of emotion, 8, 138 for schizophrenia, 436
Recall Retraining, 415
bias, from ecphoric processes, 174-175 Retrieval
depression and, 169 bias in, 184
remember/know procedure, 182 of emotional knowledge, 196-197, 200,
reminiscence effect and, 173 202f
Recreational therapist, role on rehabilitation of knowledge, 195
team, 417t of memories, 164—165
Reductive materialists, 111 as mood regulation, 177-179
Reflexes, 48 neural mechanisms in, 182-184
Regional cerebral blood flow (rCBF) as self-regulation, 176-177
in depression, 281-283 Right hemisphere
with obsessive compulsive disorder, 303 activity
electroconvulsive therapy and, 467 in anxiety, 308
energy metabolism and, 110 in panic disorder, 304
in induced sadness states, 279-281 cortical dysfunction
methodological issues, 278-279 bilateral frontal lobe, 373-374
in panic disorder, 303-304 communication deficits in, 370-372
positron emission tomography for, corticobulbar, 374
116-118, 117f dominance for emotion, 7, 216-217
Region of interest analysis, 107 emotion and, 217
Rehabilitation in emotional behavior, 226
for affective deficits, 426-427 emotional processing and, 7, 205
508 INDEX
Right hemisphere (continued) emotional expression in, 93, 434-436, 448

lesions, 205 emotional processing, neurobiological
anxiety and, 308-310 studies of, 445-447, 445-448, 446f
emotional communication and, 386 447f
emotional disorders in, 240 mania in, 439-441
emotional expression and, 183 neuropsychological features in, 440f
secondary mania and, 243 neuropsychological functioning deficits in,
in motor activation, 397-398 432-433
perception and, 269 phenomenology of, 433
stroke lesions, 250-251 recognition of emotion in, 93, 441-442,
Rorschach test, 95 442f
rTMS. See Repetitive transcranial magnetic suicide in, 436, 437
stimulation symptoms
Russell, Bertrand, 37-38, 42 clinical ratings of, 435-436
Ryle, Gilbert, 40-41 cognitive deficits, 432
hierarchical schema of, 441
SAD (seasonal affective disorder), 284, 462 negative, 434, 444—445
Sadness. See also Depression positive, 433-434, 444
depression and, 180 primary, 433
electroencephalogram studies psychotic or positive, 432
in induced states, 274 secondary, 433
methodological issues, 273-274 treatment, 442-443
induced, regional cerebral blood flow in, for depression, 443-444
279-281 of negative symptoms, 444—445
left frontal activity and, 270 of positive symptoms, 444
Scene, 6, 81 Seasonal affective disorder (SAD), 284, 462
Schemas, emotional, memory of, 168 Seizures
Schizophrenia emotional changes in, 376-377
apathy in generalized, in electroconvulsive therapy,
behavioral therapy for, 355 463-464
diagnosis of, 345-346 violence and, 323
attention in, 441f Selective serotonin reuptake inhibitors
clinical characteristics, with depression, (SSRIs)
438-439, 438t, 439t for bipolar disorder, 457
clinical features, 434-442 for depression, 457
"continuum model," 441 for Parkinson-associated depression, 381
demographics, with depression, 438-439, Self-attribution theory of emotion, 42-43
438t Self awareness, in pharmacotherapy for
depression in, 436-439, 438t, 439t, 443-444 apathy, 354
akinetic, 437 Self-concept
cerebral blood flow in, 445 in emotional appraisals, 169
cerebrospinal fluid volumes in, 445-446, memory retrieval and, 176-177
446f positive, building/maintaining, 177
glucose metabolism in, 445, 446-447, Self-evaluation, negative ruminative cycle of,
447f 172
negative symptoms and, 435, 444-445 Senile dementia of Alzheimer's disease,
pharmacogenic, 436-437 treatment of, 420
treatment of, 437-438, 443-444 Septal lesions, emotional experience and, 376
emotional deficits in, 16, 93 Serotonin (5-HIAA)
emotional disorders in, 434-436 cerebrospinal fluid levels
emotional experience in in antisocial behavior, 325-326
intensity of, 436, 437f in Parkinson's disease-associated
neuropsychology of, 436-441, 437f depression, 257
438t, 439t, 440f 44 1f in Parkinson's disease, 381
Index 509
Serotonin-reuptake inhibitors (SSRIs) SST (stereotactic subcaudate tractotomy), 473

for Huntington's disease, 383 STAI (State-Trait Anxiety Inventory), 304,
for post-stroke depression, 253-254 307
Sex differences. See Gender differences Startle response, 68-69
SFE (Social Functioning Examination), State-Trait Anxiety Inventory (STAI), 304,
259-260, 259f 307
Shame, guilt and, 180 Statistical analysis, for neuroimaging of
Single-case study, 107 emotion, 127
Single photon emission computed Stereotactically normalizing, 107
tomography (SPECT) Stereotactic subcaudate tractotomy (SST), 473
ligand, 114-115 Stimulus
in manic patients, 114-115 automatic classification, 167-168
perfusion, 115, 115f evaluation, 166
radiotracers, 114 Stress
vs. other imaging methods, 112, 113t anxiety and, 301-302
vs. PET, 116 definition of, 301
Single pulse transcranial magnetic reduction, anger and, 424
stimulation, 475 right-hemispheric processing in, 308
Skin conductance, violence and, 328-329, sources, 301-302
331 Stress inoculation approach, 425
SMA damage (supplementary motor area), Striatonigral degeneration, 384
apathy in, 348 Stroke
Social affordances, 46 bipolar disorder after, 245-246, 246f
Social apathy, 350 depression after, 246-247, 262
Social awareness, in pharmacotherapy for lesion location and, 241-242, 24 If,
apathy, 11, 354 250-252, 250/ 25 1f, 272
Social cognitive neuroscience approach, 165 longitudinal course of, 247
Social constructivist models, 149 mechanisms of, 252-253
Social emotions, 10, 20, 21 prevalence of, 247
Social functioning, 20-21 relationship to impairment, 248-250,
Social Functioning Examination (SFE), 249f
259-260, 259f severity, 272
Social functioning inventories, 81 treatment of, 253-254, 254f
Social psychology, memory and, 165 emotional changes in, 392-393
Social skills training, 14, 20, 97 emotional deficits, treatment of, 419-420,
Social worker, role on rehabilitation team, 426-427
417t lesion location
Sociocultural issues, 10 bipolar disorder and, 245, 246f
Sociopaths, aggression in, 219 depression and, 241-242, 24 1f
Somatic anxiety (anxious arousal), mania after, 240-241, 262
characteristics of, 300-301, 300t lesion location and, 241-242, 241f
Somatosensory cortices, 9, 205-208 mechanism of, 242-243
facial expression processing and, 205-206, risk factors for, 242, 243
207f, 208 treatment of, 243-244
Soul mood disorders after, cortical vs.
conceptualization of, 33, 52 subcortical lesions in, 252
tripartite, 142 unilateral right-hemisphere basal ganglia,
SPECT. See Single photon emission 92
computed tomography vocal/facial expression defects in, 223
Speech language pathologist, role on Stroop paradigm, 166-167
rehabilitation team, 417t Structured Assessment of Depression in
Speech-language therapy, approaches for, Brain-Damaged Individuals, 96
. 414-416 Study design, for neuroimaging of emotion,
SSRIs. See Serotonin-reuptake inhibitors 127
510 INDEX
Subcortical structures Theoretical perspectives, 7-11

deep, electroconvulsive stimulation of, 466 "Tick-rate" hypothesis, 173
in emotional expression, 215-216 Transcranial magnetic stimulation (TMS),
lesions, emotional expression/perception 108-109. See also rTMS
and, 91-92 electromagnetic coil, 122-123
in post-stroke mood disorders, 252 with functional imaging, 125, 126f
Subcortical (diencephalic) theories, of induced changes in normal mood, 123-124
emotional expression, 390-391 repetitive, as antidepressant, 124—125
Subjective experience. See Emotional Traumatic brain injury (TBI)
experience apathy in, pharmacotherapy for, 352
Subjective feelings depression after, 263
definition of, 155 grieving process for, 423
measurement of, 95-96, 155 impairment variables and, 260-261
Subtyping in clinical disorders, 19, 21 lesion location and, 260, 26 1f
Suicide, in schizophrenia, 436, 437 longitudinal course of, 258-259
Superior parietal gyrus, deficits, in violent risk factors for, 259-260, 259f
behavior, 324 treatment of, 261-262
Supplementary motor area damage (SMA), depression in, 258
apathy in, 348 impairment variables and, 260-261
Survival, evolutionary, 166 lesion location and, 260, 26 1f
Symptom Check List-90, 81 longitudinal course of, 258-259
Systematic desensitization, 423-424 risk factors for, 259-260, 259f
Systems-level theory of emotion, 9, 195 treatment of, 261-262
emotional deficits, 419
Tachistoscopic viewing, 5 mania after
Talairach atlas, 107 impairment variables and, 244
TBI. See Traumatic brain injury lesion location and, 245
Techniques, general, 4-7 mechanism of, 245
Telencephalon. See also Basal ganglia prevalence of, 244
evolutionary neuroanatomy, 57, 58 Trazodone, for post-stroke depression, 253
network architecture of, 59 Tricyclic antidepressants
Temporal lobe for bipolar disorder, 457
in depression with schizophrenia, 445-446, for depression, 457
446f for Parkinson-associated depression, 258,
dysfunction, violence and, 323 381
lesions for schizophrenia-associated depression,
in aggression, 323-324 443
antisocial behavior and, 324 Trihexyphenidyl, for schizophrenia negative
Temporal lobectomy, 173, 393 symptoms, 444
Temporal lobe epilepsy Truth, pragmatic theory of, 35-36
emotional changes in, 91, 376-377 Tryptophan depletion, dietary, 461-462
limbic drive mechanisms, 71-73
questionnaire, 96 Unilateral neglect syndrome, 228
'Tender-minded" philosophies, 34
Test batteries, 81-93 Valence model
Test reliability, 97 description, 7-8, 216-217
Test validity, 97 modular theory of emotional expression
Testosterone, violent behavior and, 326-327 and, 391-394
Thalamus reversed valence effect, 17
in depression, 393 transcranial magnetic stimulation studies,
emotional expression and, 390-391 123-124
intralaminar nuclei of, 397 Ventral circuit, 67
modality-specific sensory systems, 394 Ventral medial frontal cortex lesions,
Thematic Apperception Test, 95 motivational deficits and, 171
Index 511
Ventral pallidum, 223 event-related potentials, 330, 331

Ventral striatum, 223 heart rate, 329, 331
Ventromedial frontal cortices, 197 prospective research, 330-331
Verbal labels, of emotional states, 150 skin conductance, 328-329, 331
VERT (Victoria Emotion Perception Test), 86 Viral disease, emotional changes in, 376
Vertical integration, 57, 69, 74 Visceral feedback hypothesis, 388-390
Verticality Vocational counselor, role on rehabilitation
cortical vs. subcortical/limbic brain team, 417?
structures, 4 Voluntary call initiation, 69
Victoria Emotion Perception Test (VERT),
86 Wada test
Vienna Circle, 38-39 hemispheric differences in, 392
Violence left hemisphere, 271
aggressive. See Aggression in secondary mania, 243
controlled-instrumental, 320 "Weapon focus," 167, 168
hormones and, 326-328, 332t Whitehead, Alfred North, 37-38
cortisol, 327 Wilson's disease, 383-384
glucogen, 328 Wisconsin Card Sorting Task, in Parkinson
insulin, 327-328 Disease-associated depression,
testosterone, 326-327 256-257, 256f
hypoglycemia and, 327-328 Within-group analysis, 107-108
impulsive-emotional, 320 Within-individual analysis, 108
neurochemistry, 325-326, 332t Wittgenstein, Ludwig, 38, 39-40
neuropsychology, 325, 331-333, 332t
pervasiveness of, 320 Zajonc-Lazarus debate
psychophysiology, 332t arguments in, 43
description of, 328-331 LeDoux resolution of, 43-44
electroencephalogram, 330, 331 Zung Depression Inventory, 380

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The Neuropsychology of Emotion

SERIES IN AFFECTIVE SCIENCE

THE NATURE OF EMOTION

Copyright © 2000 by Oxford University Press, Inc.

Published by Oxford University Press, Inc.,

Library of Congress Cataloging-in-Publication Data

retical implications for a range of neuropsychiatric disorders, focusing on two

I am most grateful to Jeffrey House, Vice President at Oxford University Press,

Fifth, I am grateful to my mentors and colleagues who taught me so much

September 1999 J.C.B.

Part II Background and General Techniques

5. Neuroimaging Approaches to the Study of Emotion, 106

Part III Theoretical Perspectives

Part IV Emotional Disorders

Part V Clinical Implications

16. Rehabilitation of Emotional Deficits in Neurological Populations:

RALPH ADOLPHS, PH.D. DAWN BOWERS, PH.D.

RONALD L. BLOOM, PH.D. GREGORY P. CRUCIAN, PH.D.

JOAN C. BOROD, PH.D. ANTONIO R. DAMASIO, M.D.

DOUGLAS DERRYBERRY, PH.D. TlM A. KlMBRELL, M.D.

GUIDO GAINOTTI, M.D. CHRISTIAN G. KOHLER, M.D.

MARK S. GEORGE, M.D. CHRISTOPHER C. LIBERATOS, B.S.

WENDY HELLER, PH.D. PHAN Luu, PH.D.

JEFFREY HENRIQUES, PH.D. NANCY K. MADIGAN, PH.D.

TERRENCE A. KETTER, M.D. FACUNDO MANES, M.D.

GREGORY A. MILLER, PH.D. HAROLD A. SACKEIM, PH.D.

DONALD T. STUSS, PH.D. DON M. TUCKER, PH.D.

JOAN C. BOROD AND NANCY K. MADIGAN

Several critical parameters or factors must be considered in neuropsychologi-

BACKGROUND AND GENERAL TECHNIQUES

Part II provides background information about the neuropsychological study of

of performance on tasks involving emotional processing (for reviews, see Borod,

Part III, "Theoretical Perspectives," includes four chapters: Chapter 6, an over-

dimension, motor direction, suggests that withdrawal-related emotions (e.g., fear)

and cortical/subcortical distinctions. A case is made for both "top-down" (i.e.,

Part IV, "Emotional Disorders," features a spectrum of basic emotional response

orders, using electroencephalography, event-related potential, and blood flow

mental events." In support of their hypotheses, the authors provide compelling

"an absence of responsiveness to stimuli as demonstrated by a lack of self-initi-

FUTURE DIRECTIONS AND RESEARCH CONSIDERATIONS

Borod, J. (1996). Emotional disorders/emotion. In J.G. Beaumont, P. Kenealy, & M.

The overwhelming question in neurobiology today is the relation

Emotions have traditionally been regarded as extras in psychol-

Contemporary investigators interested in the relationship between mind and

philosophy.1 The chapter outlines the history of philosophical conceptualiza-

EPISTEMOLOGY AND NEUROBIOLOGY

Epistemology is the theory of the origin, structure, and validity of knowledge

Classical Roots: Monism and Dualism

C.S. Peirce is regarded by many as the founder of pragmatism. In his prag-

Peirce's pragmatic theory of meaning was borrowed and modified by William

physical universe as if it could be described in terms similar in form to those in

The Vienna Circle

The Analysis of Ordinary Language

Wittgenstein eventually abandoned the attempt to develop an ideal artificial

Gilbert Ryie: The ghost in the machine

EMOTIONAL AND COGNITIVE KNOWLEDGE

Level of Brain Processing

In 1927, Bertrand Russell anticipated a major contemporary theory of emotion

Speed of Brain Processing

The Zajonc-Lazarus debate