Background

Anxious youth have shown altered behavioral performance on the dot-probe task, but neural activation patterns provoked by the task remain poorly understood. In particular, neural mechanisms of threat disengagement, a clinically relevant construct, have been inadequately explored.

Method

During fMRI acquisition, 121 youth (ages 9-13; 90 with Generalized Anxiety Disorder, Separation Anxiety Disorder, and/or Social Phobia; 31 nonanxious controls) completed a dot-probe task, which required participants to identify the location of a dot replacing either a neutral or fearful face in a pair containing both faces. We assessed neural substrates of threat disengagement by comparing congruent trials (in which the dot replaces the fearful face) to incongruent trials (in which the dot replaces the neutral face).

Results

Across subjects, decreased rostrodorsal anterior cingulate cortex (rdACC) activity was observed specifically during incongruent trials. Nonanxious youth showed a convergent pattern in bilateral parahippocampal and hippocampal regions, whereas anxious youth showed an opposing pattern in these limbic areas, suggesting less integration of response across cortical and limbic areas relevant to threat appraisal. Reduced functional connectivity between rdACC and left parahippocampus/hippocampus was associated with greater anxiety.

Conclusions

In the largest dot-probe fMRI sample to date, both anxious and nonanxious youth showed a neural pattern consistent with successful disengagement of threat reactivity in the rdACC. However, anxious youth showed evidence of abnormal disengagement in bilateral parahippocampal/hippocampal clusters when attention was directed away from threat. Early interventions targeting neural mechanisms of threat disengagement may be beneficial, for example, by increasing integration across rdACC and limbic regions.

Anxious youth are at heightened risk for subsequent development of depression; however, little is known regarding which anxious youth are at the highest prospective risk. Biased attentional patterns (e.g., vigilance and avoidance of negative cues) are implicated as key mechanisms in both anxiety and depression. Aberrant attentional patterns may disrupt opportunities to effectively engage with, and learn from, threatening aspects of the environment during development and/or treatment, compounding risk over time. Sixty-seven anxious youth (ages 9-14; 36 female) completed a dot-probe task to assess baseline attentional patterns provoked by fearful-neutral face pairs. The time course of attentional patterns both during and after threat was assessed via eye-tracking and pupilometry. Self-reported depressive and anxiety symptoms were assessed 2 years after the conclusion of a larger psychotherapy treatment trial. Eye-tracking patterns indicating threat avoidance predicted greater 2-year depression scores, over and above baseline and posttreatment symptoms. Sustained, postthreat pupillary avoidance (reflecting preferential neural engagement with the neutral relative to the previously threatening location) predicted additional variance in depression scores, suggesting sustained avoidance in the wake of threat further exacerbated risk. Identical eye-tracking and pupil indices were not predictive of anxiety at 2 years. These biobehavioral markers imply that avoidant attentional processing in the context of anxiety may be a gateway to depression across a key maturational window. Excessive avoidance of threat could interfere with acquisition of adaptive emotion regulation skills during development, culminating in the broad behavioral deactivation that typifies depression. Prevention efforts explicitly targeting avoidant attentional patterns may be warranted.

Vigilance and avoidance of threat are observed in anxious adults during laboratory tasks, and are posited to have real-world clinical relevance, but data are mixed in anxious youth. We propose that vigilance-avoidance patterns will become evident in anxious youth through a focus on individual differences and real-world strategic avoidance. Decreased functional connectivity between the amygdala and prefrontal cortex (PFC) could play a mechanistic role in this link. 78 clinically anxious youth completed a dot-probe task to assess vigilance to threat while undergoing fMRI. Real-world avoidance was assessed using Ecological Momentary Assessment (EMA) of self-reported suppression and distraction during negative life events. Vigilance toward threat was positively associated with EMA distraction and suppression. Functional connectivity between a right amygdala seed region and dorsomedial and right dorsolateral PFC regions was inversely related to EMA distraction. Dorsolateral PFC-amygdalar connectivity statistically mediated the relationship between attentional vigilance and real-world distraction. Findings suggest anxious youth showing attentional vigilance toward threat are more likely to use suppression and distraction to regulate negative emotions. Reduced PFC control over limbic reactivity is a possible neural substrate of this pattern. These findings lend ecological validity to laboratory vigilance assessments and suggest PFC-amygdalar connectivity is a neural mechanism bridging laboratory and naturalistic contexts.

The dot-probe task has been widely used in research to produce an index of biased attention based on reaction times (RTs). Despite its popularity, very few published studies have examined psychometric properties of the task, including test-retest reliability, and no previous study has examined reliability in clinically anxious samples or systematically explored the effects of task design and analysis decisions on reliability. In the current analysis, we used dot-probe data from 3 studies in which attention bias toward threat-related faces was assessed at multiple (≥5) time-points. Two of the studies were similar (adults with social anxiety disorder, similar design features) whereas 1 was more disparate (pediatric healthy volunteers, distinct task design). We explored the effects of analysis choices (e.g., bias score formula, outlier handling method) on reliability and searched for convergent findings across the 3 studies. We found that, when concurrently considering the 3 studies, the most reliable RT index of bias used data from dot-bottom trials, comparing congruent to incongruent trials, with rescaled outliers, particularly after averaging across more than 1 assessment point. Although reliability of RT bias indices was moderate to low, within-session variability in bias (attention bias variability; ABV), a recently proposed RT index, was more reliable across sessions. Several eyetracking-based indices of attention bias (available in the pediatric healthy sample only) showed reliability that matched the optimal RT index (ABV). On the basis of these findings, we make specific recommendations to researchers using the dot-probe, particularly those wishing to investigate individual differences and/or single-patient applications.

BACKGROUND:Vigilant attention to threat is commonly observed in anxiety, undergoes developmental changes in early adolescence, and has been proposed to interfere with sleep initiation and maintenance. We present one of the first studies to use objective measures to examine associations between vigilant attention to threat and difficulties initiating and maintaining sleep in an early adolescent anxious sample. We also explore the moderating role of development (age, puberty) and sex. METHODS:Participants were 66 peripubertal youth (ages 9-14) with a primary anxiety disorder and 24 healthy control subjects. A dot-probe task was used to assess attentional bias to fearful relative to neutral face stimuli. Eye-tracking indexed selective attentional bias to threat, and reaction time bias indexed action readiness to threat. Sleep was assessed via actigraphy (e.g. sleep onset delay, wake after sleep onset, etc.), parent report (Children's Sleep Habits Questionnaire), and child report (Sleep Self-Report). The Pediatric Anxiety Rating Scale assessed anxiety severity. RESULTS:Eye-tracking initial threat fixation bias (β = .33, p = .001) and threat dwell time bias (β = .22, p = .041) were positively associated with sleep onset latency. Reaction time bias was positively associated with wake after sleep onset (β = .24, p = .026) and parent-reported sleep disturbance (β = .25, p = .019). Anxiety (severity, diagnosis) was not associated with these outcomes. Sex (β = -.32, p = .036) moderated the relation between initial threat fixation bias and sleep onset latency, with a positive association for males (p = .005), but not for females (p = .289). Age and pubertal status did not moderate effects. CONCLUSIONS:Vigilant attention to threat is related to longer sleep onset and reduced sleep maintenance. These associations are not stronger in early adolescents with anxiety. Implications for early intervention or prevention that targets vigilant attention to threat to impact sleep disturbance, and vice versa, are discussed.

During adolescence, youth may experience heightened attention bias to socially relevant stimuli; however, it is unclear if attention bias toward social threat may be exacerbated for adolescents with a history of anxiety. This study evaluated attentional bias during the Chatroom-Interact task with 25 adolescents with a history of anxiety (18F, Mage = 13.6) and 22 healthy adolescents (13F, Mage = 13.8). In this task, participants received feedback from fictional, virtual peers who either chose them (acceptance) or rejected them (rejection). Overall, participants were faster to orient toward and spent longer time dwelling on their own picture after both rejection and acceptance compared to non-feedback cues. Social feedback was associated with greater pupillary reactivity, an index of cognitive and emotional neural processing, compared to non-feedback cues. During acceptance feedback (but not during rejection feedback), anxious youth displayed greater pupil response compared to healthy youth, suggesting that positive feedback from peers may differentially influence youth with a history of an anxiety disorder.

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5-90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.