Cole 2018

Journal of Autism and Developmental Disorders
https://doi.org/10.1007/s10803-018-3492-2
ORIGINAL PAPER
Investigating Mirror System (MS) Activity in Adults with ASD When

Inferring Others’ Intentions Using Both TMS and EEG
Eleanor J. Cole1 · Nick E. Barraclough1 · Peter G. Enticott2
© The Author(s) 2018. This article is an open access publication
Abstract
ASD is associated with mentalizing deficits that may correspond with atypical mirror system (MS) activation. We investigated
MS activity in adults with and without ASD when inferring others’ intentions using TMS-induced motor evoked potentials
(MEPs) and mu suppression measured by EEG. Autistic traits were measured for all participants. Our EEG data show, high
levels of autistic traits predicted reduced right mu (8–10 Hz) suppression when mentalizing. Higher left mu (8–10 Hz) sup-
pression was associated with superior mentalizing performances. Eye-tracking and TMS data showed no differences associ-
ated with autistic traits. Our data suggest ASD is associated with reduced right MS activity when mentalizing, TMS-induced
MEPs and mu suppression measure different aspects of MS functioning and the MS is directly involved in inferring intentions.
Keywords Autism spectrum disorder (ASD) · Mirror system (MS) · Mentalizing · Transcranial magnetic stimulation
(TMS) · Electroencephalography (EEG) · Intentions
Introduction of autistic traits. Individuals without an ASD diagnosis but

who display relatively high levels of autistic traits have also
Experimental evidence and anecdotal reports suggest that been shown to exhibit mentalizing deficits (Gökçen et al.
individuals with autism spectrum disorder (ASD) diagnoses 2014, 2016).
display difficulties inferring the thoughts, feeling and beliefs The ‘broken mirror’ theory of ASD suggests that dys-
of others, collectively known as ‘mentalizing’ (Baron-Cohen function in brain areas known collectively as the mirror
et al. 1997; Castelli et al. 2002; Jolliffe and Baron-Cohen system (MS) underlie some of the social communication
1999; Kana et al. 2014; Senju et al. 2009). ASD is a term difficulties experienced by individuals with ASD (Iacoboni
used by the most recent edition of the Diagnostic and Sta- and Dapretto 2006; Oberman and Ramachandran 2007). The
tistical Manual of Mental Disorders (DSM-5) to describe main components of the human MS are considered to be the
a number of neurodevelopmental disorders characterised inferior frontal gyrus (IFG) and the inferior parietal lobe
by difficulties in social communication as well as restricted (IPL; Rizzolatti and Craighero 2004; Rizzolatti and Sini-
and repetitive behaviours (American Psychiatric Associa- gaglia 2010). Areas of the MS are active during the per-
tion 2013). Due to the spectral nature of ASD, individuals formance of an action as well as the observation of similar
with and without ASD diagnoses display varying degrees actions (di Pellegrino et al. 1992; Rizzolatti et al. 1996). It is
thought that by displaying similar activation patterns during
Electronic supplementary material The online version of this the observation of actions as when performing actions, the
article (https://doi.org/10.1007/s10803-018-3492-2) contains MS simulates observed actions in the observer’s own motor
supplementary material, which is available to authorized users. system to facilitate action understanding (Rizzolatti and
Craighero 2004). This is known as the motor resonance the-
* Eleanor J. Cole
[email protected] ory (Agnew et al. 2007; Landmann et al. 2011; Leslie et al.
2004; Rizzolatti et al. 2002). According to the broken mir-
1
The Department of Psychology, The University of York, ror theory, atypical MS activation in individuals with ASD
Heslington, York, North Yorkshire YO10 5DD, UK results in reduced understanding of the actions of others,
2
Cognitive Neuroscience Unit, Faculty of Health, Deakin which in turn underlies some of the social communication
University Burwood Campus, 221 Burwood Highway,
Melbourne, VIC 3125, Australia
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Vol.:(0123456789)
difficulties these individuals experience (Iacoboni and atypical in adults with ASD when the mentalizing system is
Dapretto 2006; Oberman and Ramachandran 2007). engaged. Therefore, it is possible that reduced MS activity
Although the broken mirror hypothesis is an attractive during mentalizing tasks may contribute to the mentalizing
theory, the literature supporting the possibility of atypi- difficulties these adults experience.
cal MS activation in individuals with ASD is limited, par- Despite numerous studies providing evidence for a role
ticularly in adults. A number of behavioural studies, fMRI of the MS in mentalizing, some fMRI studies have not
studies and studies using electromyographic recordings have found higher levels of MS activity during mentalizing tasks
shown children with ASD display both behavioural impair- compared to non-mentalizing tasks in typically develop-
ments and atypical MS activity during tasks typically associ- ing participants (Castelli et al. 2000, 2002; Gallagher et al.
ated with MS functioning such as imitation (Dapretto et al. 2000; Spunt et al. 2011; White et al. 2014). Differences in
2006; Hobson and Hobson 2008; Rogers et al. 2003; Wil- the stimuli used are likely to have contributed to inconsist-
liams et al. 2004), action planning (Cattaneo et al. 2007; encies in the existing literature. fMRI studies have shown
Dowd et al. 2012; Fabbri-Destro et al. 2009) and gestural that different brain areas are active during mentalizing tasks
performance (Dewey et al. 2007). In contrast, adults with depending on the stimuli used (Gobbini et al. 2007; Schurz
ASD generally display typical behavioural performances et al. 2014), higher MS activation is elicited when dynamic
on tasks traditionally associated with MS functioning (Bird stimuli are used rather than static stimuli and when stimuli
et al. 2007; Avikainen et al. 2003) and the majority of depict bodies rather than faces (Schlochtermeier et al. 2015).
neuroimaging studies (fMRI, EEG and TMS) have shown The majority of mentalizing tasks that have not elicited MS
that adults with ASD display typical levels of MS activity activation have used simplistic cartoons, still images or pas-
(Avikainen et al. 1999; Dinstein et al. 2010; Enticott et al. sages of text as stimuli (Castelli et al. 2000, 2002; Gallagher
2013b; Marsh and Hamilton 2011). Only a limited number et al. 2000; White et al. 2014). If MS functioning is atypi-
of studies have provided evidence to suggest MS activation cal in adults with ASD during mentalizing tasks then these
is atypical during these tasks in adults with ASD (Bernier individuals may display more prominent differences in brain
et al. 2007; Enticott et al. 2012; Honaga et al. 2010; Mar- activation and greater behavioural impairments on mental-
tineau et al. 2010) and adults with high levels of autistic izing tasks that typically elicit greater levels of MS activity.
traits (Cooper et al. 2013; Lepage et al. 2010; Puzzo et al. Transcranial magnetic stimulation (TMS) and electroen-
2009). Therefore, evidence to support general dysfunction of cephalography (EEG) are two techniques that have often
the MS in ASD, particularly in adults, is limited (Hamilton been used to non-invasively obtain indirect indices of MS
2013). activity, but it is unknown precisely how these two indices
Despite the limited evidence suggesting atypical MS of MS activity relate to each other. TMS involves adminis-
activity in adults with ASD during tasks traditionally tering brief magnetic pulses through a magnetic coil placed
associated with MS functioning (e.g. imitation and action on the scalp in order to induce transient changes in activity
planning), fMRI studies have found reduced MS activation in the underlying region of the cortex (Hallett 2000). When
(IFG and IPL) in adults with ASD during mentalizing tasks single TMS pulses are applied to the primary motor cortex
compared to control participants (Baron-Cohen et al. 1999; (M1), the resulting increases in corticospinal activity can
Holt et al. 2014; Kana et al. 2014). A wide body of neuro- be measured by recording increased activity in contralat-
imaging literature has provided evidence for MS involve- eral hand muscles via electromyography (EMG; Aziz-Zadeh
ment in mentalizing in typically developing adults: higher et al. 2002; Fadiga et al. 2005). These increases in muscle
MS activity has been shown during mentalizing tasks than activity induced by TMS (known as motor evoked poten-
non-mentalizing tasks (fMRI; Adams et al. 2010; Centelles tials; MEPs) are larger when individuals view hand actions
et al. 2011; de Lange et al. 2008; Schurz et al. 2014; PET; compared to when TMS is applied at rest and therefore
Brunet et al. 2000). Additionally, both fMRI and TMS stud- these increases in MEP sizes during action observation are
ies have found higher MS activation during the observa- regarded as an index of MS activity (Fadiga et al. 2005;
tion of actions with social context compared to non-social Patuzzo et al. 2003; Strafella and Paus 2000). In contrast, mu
actions even in the absence of mentalizing tasks (Bucchioni rhythm; large amplitude oscillations in the alpha frequency
et al. 2013; Ciaramidaro et al. 2014; Enticott et al. 2013b; band (8–12 Hz) over sensorimotor cortex detected by EEG,
Iacoboni et al. 2004). Lesions to IFG, both in brain damaged is suppressed during action observation as well as the per-
patients (Besharati et al. 2016; Dal Monte et al. 2014) and formance of actions and thereby provides another index of
when temporary functional lesions are induced via direct MS activity (Fox et al. 2016; Frenkel-Toledo et al. 2014;
current stimulation in patients undergoing surgery to treat Oberman et al. 2007). Two previous studies that have com-
epilepsy (Herbet et al. 2014), have been shown to impair bined EEG and single-pulse TMS to measure MS activity in
mentalizing performances. Collectively, these data show that typically developing populations have shown that although
MS has a role in mentalizing and that MS functioning is measurements from both these techniques are sensitive to
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motor resonance mechanisms, they are not correlated with reduced task-related changes in MS activity and that lower
each other (Andrews et al. 2015; Lepage et al. 2008). There- levels of MS activity would be related to poorer mentalizing
fore, it is possible that these measurements reflect different performances.
aspects of MS functioning. It is important to note that these
indices of MS activity also differ in their spatial and tempo-
ral properties; EEG measures the sum of post-synaptic neu- Methods
ronal activity over a large area, and an index of mu suppres-
sion is typically taken over a relatively long time period (i.e., Participants
> 1 s). By contrast, TMS measures brief induced increases
in corticospinal activity from peripheral muscles (Andrews Forty-three adults were recruited for this study, of which 13
et al. 2015; Pineda 2005; Rossini et al. 1994). Using both had a formal diagnosis of either Asperger’s disorder (11)
of these non-invasive measures of MS activity simultane- or ASD. All of the participants with a diagnosis met the
ously allows a more complete picture of MS functioning to DSM-5 criteria for ASD and none of the participants had
be collected. any existing learning difficulties or experienced delayed
This study aimed to investigate whether adults with diag- language development. Participants without an ASD diag-
noses of ASD display atypical MS activity when mentalizing nosis were recruited based on the level of autistic traits they
and whether levels of MS activation correspond to mental- displayed as measured by the Autistic Spectrum Quotient
izing performance. In this study, participants watched hand (AQ; Baron-Cohen et al. 2001). The average AQ score in the
action videos, and after each video they had to either make general population is 16.94 (Ruzich et al. 2015). Individuals
decisions about the intention of the actor (mentalizing task) were excluded from the study if they had AQ scores between
or the success of the action (non-mentalizing task). The 16 and 19. Participants with scores between 0 and 15 were
video stimuli used showed different actors performing natu- assigned to the ‘low AQ’ group and participants with AQ
ralistic hand actions to ensure the stimuli were sufficiently scores of 20 or higher were assigned to the ‘high AQ’ group.
complex and optimally activated the MS. TMS-induced This resulted in three participant groups: low AQ (n = 15),
MEPs and mu suppression were both used as indices of MS high AQ (n = 15) and ASD (n = 13). Participants without an
activity. A preliminary TMS study carried out on typically ASD diagnosis were grouped into low and high AQ groups
developing individuals, using the same stimuli, identified due to findings of subtler versions of the behavioural and
higher MS activation during a mentalizing task compared neural characteristics associated with ASD in individuals
to a non-mentalizing task once the actors’ intentions had without a diagnosis but relatively high levels of autistic traits
been revealed (Cole and Barraclough 2017). Therefore, in (Best et al. 2015; Di Martino et al. 2009; Lindell et al. 2009;
our study, single-pulse TMS was applied to the primary Ridley et al. 2011; van Boxtel and Lu 2013). AQ scores were
motor cortex (M1) at the end of each hand action when the used to group these individuals initially and further psycho-
outcome of the action or the intention of the actor had been logical assessments were later used to quantify the level of
revealed. Simultaneous EEG recordings were made through- autistic traits displayed in more detail (see Psychological
out the experiment. Participants without a diagnosis were Assessments). The participant groups did not significantly
grouped based on low or high levels of autistic traits. It was differ in age, verbal IQ, gender or years of formal education
predicted that larger TMS-induced MEP sizes and greater and all participants had verbal IQ scores within the normal
levels of mu suppression would be found during the men- range (> 70; see Table 1).
talizing task compared to the non-mentalizing task, indi- All participants were screened for symptoms of psychi-
cating higher levels of MS activity. It was also predicted atric disorders using the Mini-International Neuropsychi-
that high levels of autistic traits would be associated with atric Interview (MINI) (Sheehan et al. 1998). Individuals
Table 1 Demographic Low AQ High AQ ASD p ηp2

information; group mean (SD)
values N 15 15 13
Age 23.40 (6.82) 24.13(4.68) 28.30 (9.40) 0.16 0.09
Gender (m:f) 8:7 7:8 9:4 0.47 (X2) /
Years of formal 15.60 (1.64) 16.20 (1.66) 15.38 (1.45) 0.37 0.05
education
Verbal IQa 109.67 (14.09) 113.00 (9.22) 111.62 (14.98) 0.78 0.01
p values were obtained from one-way MANOVA unless otherwise stated

a
The verbal IQ scores were measured using the test of pre-morbid functioning
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Table 2 Medication information for participants in the ASD group Table 3 Participants’ psychological test scores; group mean (SD) val-
ues
Participant Medication (daily dosage)
Low AQ High AQ ASD p ηpb
1 Dexamphetamine (20 mg),
Zoloft (150 mg) AQ 8.80 (4.38) 24.07 (4.27) 32.00 (6.67) < 0.001 0.79
2 Dexamphetamine (20 mg) EQ 53.07 (11.82) 42.60 (13.61) 27.23 (12.09) < 0.001 0.43
3 Ritalin (30 mg) TASITa 58.73 (3.10) 54.07 (4.13) 52.38 (5.49) 0.001 0.30
4 Valium (5 mg when needed) ADOS-2 1.40 (0.99) 4.67 (1.40) 8.54 (3.28) < 0.001 0.78
5 Zoloft (50 mg) SRS-2b 27.87 (15.70) 58.60 (19.10) 101.46 < 0.001 0.69
6 Zoloft (50 mg) (26.00)
a
The TASIT scores were obtained from part 3 (social inference test)
b
The reported SRS-2 scores are the unstandardized, raw scores,
were not eligible to take part if they were diagnosed with where scores above 60 indicate some social impairment and scores
above 75 reflect severe social impairment
any psychiatric disorders or were identified by the MINI
as displaying symptoms of any psychiatric disorders. An
exception was made for mood disorders, anxiety and ADHD separate date to the TMS session and both sessions were
in the participants with ASD due to the high prevalence of completed within a 2 week time frame.
these comorbidities (Matson et al. 2013; Matson and Wil-
liams 2014). In the ASD group, six participants were taking Experimental Set‑Up
psychotropic medication to treat ADHD, depression or anxi-
ety (see Table 2). None of the participants without an ASD Participants sat 600 mm away from an Eyelink 1000 plus
diagnosis were taking psychotropic medication. eye-tracker (SR Research, Ontario) placed in front of a
Participants were also screened for contraindications for 24″ LED computer monitor. Single EEG electrodes were
TMS; history of seizures, serious head injuries, brain related placed at locations FCz, F3 and F4 according to the inter-
conditions, severe headaches, implanted metal or medical national 10–20 system of electrode placement. Typically,
devices, family history of epilepsy and current pregnancy EEG recordings are taken from central electrodes (C3, C4,
(Rossi et al. 2009). Cz) when investigating MS activity. However, due to the
This research project was approved by the Human placement of the TMS coil over the primary motor cortex
Research Ethics Committee at Deakin University and was (M1) EEG recordings were taken from frontal electrodes
performed in accordance with the ethical standards laid (F3, F4, FCz) to reduce TMS-induced artefacts, and to allow
down in the 1990 Declaration of Helsinki. All participants sufficient contact between the TMS coil and the scalp. It has
provided signed informed consent. previously been shown that mu suppression can be measured
across the entire scalp when observing and imitating hand
Psychological Assessments actions and ASD participants have been shown to display
differences in mu power over frontal regions (Dumas et al.
All participants completed the Autism Spectrum Quotient 2014). Reference electrodes were placed on the left and right
(AQ), Autism Diagnostic Observation Schedule (ADOS- mastoid bones and the ground electrode was placed on the
2), The Awareness of Social Inference Test (TASIT), Social forehead. Electrooculogram (EOG) electrodes were placed
Responsiveness Scale (SRS-2) and Empathy Quotient (EQ). above and below the left eye to in order to identify EEG arte-
The AQ and ADOS-2 are designed to measure the level of facts caused by blinking. EEG signals were recorded using
autistic traits displayed, the SRS-2 and TASIT measure Curry Neuroimaging Suite 7 (Compumetics Ltd, Australia).
social functioning and the EQ provides a measure of empa- EEG signals were amplified using NeuroScan SynAmps RT
thy. The three groups significantly differed from each other (NeuroScan SynAmps, Compumedics Ltd.) and digitised at
on all these measures (see Table 3). These psychological 1 kHz. All electrode impedances were below 5 KΩ. EEG
tests have been shown to display good psychometric proper- analyses and bandpass filtering were conducted offline.
ties (Allison et al. 2011; Hurst et al. 2007; McDonald et al. TMS was administered using a Magstim BiStim2 stimula-
2006; Oosterling et al. 2010). The AQ was administered in tor (Magstim Company Ltd., Carmarthenshire, Wales, UK).
the form of an online questionnaire before the participants Firstly, the location of the primary motor cortex (M1) was
took part in the experiment. The other assessments were identified in each participant by measuring the position on
administered at the Cognitive Neuroscience Unit at Deakin the scalp five centimetres lateral and 1 cm anterior to Cz
University as a 2-h session prior to the TMS testing session. (according to the international 10–20 system of electrode
Psychological assessment sessions always took place on a placement). TMS pulses were then applied to this position
on the scalp using a standard figure of eight 70 mm coil
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held tangentially over the scalp at a 45° angle to the mid- their left hand. In the mentalizing task, participants watched
line. An initial intensity of 40% stimulator output was used videos that either showed an actor accidentally dropping a
and then the intensity of TMS stimulation was increased in poker chip and therefore failing to pass the poker chip to
5% increments until MEPs were produced. Stimulation was the other player (‘clumsy’ action) or an actor deliberately
also applied around the estimated location of M1 in order to not passing the poker chip (‘spiteful’ action). After each
confirm that this was the optimal scalp location to produce video, participants indicated whether they thought the action
MEPs in muscles of the right hand. MEPs were measured was ‘clumsy’ or ‘spiteful’. In the non-mentalizing block,
from the first dorsal interosseous (FDI) and abductor digiti participants watched videos in which actors either success-
minimi (ADM) muscles using Ag/AgCl surface electrodes. fully passed the poker chip to the other player (successful
EMG signals were amplified using PowerLab 4/35 (with action) or accidentally dropped the poker chip (unsuccess-
dual BioAmp; AD Instruments, Colorado Springs, CO). ful action). After each video, participants had to indicate
Once the optimal location for stimulation had been iden- whether the action was ‘successful’ or ‘unsuccessful’. The
tified, the intensity of the TMS stimulation was adjusted unsuccessful actions shown in the non-mentalizing block
in order to find the participants’ resting motor threshold were the same as the ‘clumsy’ actions shown in the mental-
(RMT). Participants’ RMT was defined as the minimum izing block. Before each block, participants were told which
stimulation intensity needed to induce MEPs with an average decision they would be required to make after each video in
peak-to-peak magnitude of 1 mV over 5 consecutive trials. the upcoming block (the instructions given to participants
Twenty MEPs induced by stimulation at RMT were used as are available in the supplementary material). Participants
a measure of baseline corticospinal excitability (CSE). also completed 16 practice trials (8 mentalizing trials) before
the main experiment so that they knew what the tasks would
Experimental Task entail. The actors shown in the practice trials were not shown
in the main experiment to avoid any preconceptions about
The experiment comprised of two blocks; a mentalizing the actors influencing decisions made in the main experi-
task and a non-mentalizing task. In both tasks, participants ment. The videos shown in this experiment are a subset
watched short videos (4 s) of actors passing or attempting of the videos used in a previous study (Cole et al. 2017).
to pass a poker chip through slots in a wooden board to Grasping and pushing actions were shown; grasping actions
another person on the other side of the board (who was out involved actors grasping a poker chip and placing it through
of view; see Fig. 1). After each video, participants were a slot at head height, pushing actions involved pushing the
asked to make a decision about the action; either about the poker chip with the index finger through a slot that was level
intention of the actor (mentalizing task) or the success of the with the table in front of them (see Fig. 1). Twenty actors (10
action (non-mentalizing task). Participants indicated their male) were shown performing each action (clumsy grasp,
response by pressing buttons on the computer keyboard with clumsy push, spiteful grasp, spiteful push, successful grasp,
Fig. 1 Screenshots depicting the final frame of the video stimuli for (successful grasp). d Accidentally not passing a poker chip through
one actor. The videos depict an actor: a Accidently dropping a poker the bottom slot (clumsy push). e Deliberately not passing a poker
chip (clumsy grasp). b Deliberately dropping a poker chip (spiteful chip through the bottom slot (spiteful push). f Passing a poker chip
grasp). c Passing a poker chip through the higher slot in the board through the bottom slot (successful push)
13
successful push) resulting in 80 action videos in each of the were removed from the analysis (4.02% of all MEPs were
two blocks (clumsy actions were seen in both blocks). Two excluded). Two participants in the high AQ group were
types of actions (grasping and pushing) were used in order removed from the analyses for having only 50% or fewer
to make the stimuli more varied and these particular actions valid FDI MEPs for either task. This resulted in 35 partici-
were chosen as they both utilise the FDI muscle. pants (15 low AQ, 11 high AQ and 9 ASD) being included
A single TMS pulse at 1 mV RMT was delivered at the in the EMG analysis.
end of each video. A light sensor was used in order to time Preliminary analyses were carried out on the EMG data
lock the TMS pulses to the timing of the videos. A black in order to clarify that RMTs were not significantly different
square was added to the top left corner of the videos and between groups, that the experiment did not alter partici-
this black square was replaced with a white square for the pants’ resting corticospinal activity and that the number of
last three frames in each video. The light sensor detected this excluded MEPs did not significantly differ across tasks or
change and sent a 5 V TTL pulse to the TMS stimulator via participant groups. Group differences in RMTs were inves-
a BNC cable which triggered a single TMS pulse to be fired. tigated using a one-way ANOVA. Changes in corticospinal
The TMS machine subsequently sent a trigger to a PowerLab activity as a result of the experiment were investigated by
4/35 (ADInstruments Pty Ltd) to trigger EMG recording. first calculating median MEP sizes (peak-to-peak amplitude
EEG was continuously recorded throughout both the men- [mV]) for both the 20 single TMS pulses given before the
talizing and non-mentalizing tasks but triggers were sent experiment and after the experiment for both muscles. Then,
to the EEG machine at the start of each trial to record the separate mixed-model ANOVAs were performed for each
type of action being shown. The order in which mentalizing muscle investigating the influences of group (low AQ, high
and non-mentalizing blocks were completed was counter- AQ, ASD) and time point (before or after the experiment)
balanced across all participants and within each participant on MEP sizes. The data regarding the number of excluded
group. Once participants had completed both the mentaliz- MEPs violated the assumption of normality even after a log
ing and the non-mentalizing task, twenty single TMS pulses transformation was applied so non-parametric tests were
were administered at RMT in order to compare baseline cor- used. An independent-samples Kruskal–Wallis test was used
ticospinal excitability before and after the experiment. to investigate group differences and a related-samples Wil-
coxon signed rank test was used to investigate differences in
Behavioural Analysis the number of MEPs excluded between tasks.
For the main TMS data analyses, median MEP values
First, the ADOS-2, AQ, EQ, SRS-2 and TASIT scores were were calculated for both the FDI and the ADM muscles for
calculated and a one-way MANOVA was used to identify each participant and each task (mentalizing/non-mentaliz-
group differences in these scores. Then, the numbers of cor- ing). Median baseline MEP values were also calculated for
rect responses on the mentalizing and non-mentalizing tasks both muscles for each participant by combining MEPs from
were calculated for each participant. Data screening identi- both pre- and post-experiment baseline measures. The raw
fied that the behavioural data were not normally distributed median MEP values for each task were then converted into
and therefore a log transformation was applied. The log motor resonance values by computing the relative MEP sizes
transformed data still violated the assumption of normality in comparison to MEP sizes at baseline:
so non-parametric analyses were conducted. Potential group [
MR = (median MEP during task − median MEP at baseline)∕
differences in behavioural performances were explored using
a Kruskal–Wallis test and a possible task-related difference median MEP at baseline] ∗ 100
in performances across all participants was examined using
Data screening found that the motor resonance data for
a Wilcoxon signed rank test.
both FDI and ADM muscles violated the assumption of nor-
mality so a log transformation was used. This transformation
EMG Analysis
cannot be performed on negative values so a constant of 100
was added to each motor resonance value prior to trans-
TMS was not performed on two participants in the high
formation to ensure that all values were positive. After the
AQ group and four participants in the ASD group; two par-
log transformation, the distribution of the FDI data did not
ticipants in the ASD group and one participant in the high
significantly differ from a normal distribution but the ADM
AQ group found TMS too uncomfortable and the remain-
data still violated the assumption of normality. Therefore,
ing three participants had motor thresholds deemed too
parametric analyses were used for the log transformed FDI
high to continue (> 75% stimulator output). Trials in which
data, but non-parametric analyses were conducted on the log
muscle activity (± 0.1 mv) was identified within a 200 ms
transformed ADM muscle data.
time window before the TMS pulse or trials in which FDI
peak to peak MEP amplitudes were smaller than 0.2 mV
13
The FDI motor resonance data were analysed using were conducted. A Kruskal–Wallis test was used to investi-
a mixed-model ANOVA to investigate the influences of gate group differences in the number of epochs excluded and
group (low AQ, high AQ, ASD) and task (mentalizing/non- a Friedman’s ANOVA was used to identify differences in the
mentalizing) on MEP sizes. Potential group differences in number of excluded epochs across experimental conditions.
the ADM motor resonance data were investigated using a A Fast Fourier Transform (FFT) was used to calculate mu
Kruskal–Wallis test and potential differences in motor res- power in both the low alpha frequency range (8–10 Hz) and
onances across experimental tasks were explored using a high alpha frequency range (10–12 Hz) during all epochs.
Wilcoxon signed rank test. The majority of previous studies investigating MS activity
using EEG have used activity in the entire alpha frequency
band (8–12/13 Hz) as a measure of mu power (Andrews et al.
EEG Analysis 2015; Oberman et al. 2005, 2008; Perry et al. 2011; Ulloa
and Pineda 2007). However, there is accumulating evidence
Offline analyses of the EEG data were performed using to suggest that lower (8–10 Hz) and higher (10–12 Hz) alpha
Curry 7 Neuroimaging Suite software (Compumetics Ltd, bands reflect different processes and should therefore be ana-
Australia). Epochs of EEG data were created for videos lysed separately (Dumas et al. 2014; Frenkel-Toledo et al.
shown in each task (mentalizing and non-mentalizing). 2014; Neuper et al. 2009; Pfurtscheller et al. 2000). Addi-
Although, the action videos were 4000 ms long, the last tionally, a previous study found reduced mu suppression in
350 ms of each epoch was removed in order to eliminate the the 10–12 Hz range over frontal regions in adults with ASD
artefact created by the TMS pulse. Therefore, each video but not the 8–10 Hz range when observing hand movements
epoch was 3650 ms long and 80 epochs of each type were (Dumas et al. 2014). Consequently, lower and higher mu
created for every participant. EEG data collected when frequency bands were analysed separately in this study.
participants were viewing a fixation cross were used as a Average mu power in both frequency bands was then cal-
baseline measure. There were 160 fixation cross epochs (80 culated for each epoch type (four epoch types: mentalizing
for each task), each 1500 ms long. The first 500 ms of each videos, non-mentalizing videos, mentalizing fixation and
fixation cross epoch were removed from the analysis because non-mentalizing fixation) for every participant. The degree
the fixation cross was shown directly after participants were of mu suppression during each experimental condition was
required to make a response and therefore removing the calculated by comparing average mu power during the video
first 500 ms reduced the possibility of increased mu power epochs compared to the fixation epochs in the same condi-
during fixation as a result of participants moving their left tion: [(fixation-video)/fixation]*100. Larger values indicated
hand back to a resting position after they had made their greater degrees of mu suppression. The mu suppression data
responses. This resulted in 160 fixation epochs for each par- for both frequency bands violated the assumption of nor-
ticipant that were each 1000 ms long. mality so the data were log transformed. Log transforma-
EEG data were baseline corrected and band-pass filtered tions cannot be carried out on negative values so a con-
(1–30 Hz). Blink artefacts were detected by scanning the stant of 1300 was added to each data point to ensure that all
data from the EOG electrodes for voltages greater than 100 values were positive before the log transformation. After
or − 100 µV. Once the blink artefacts were detected, these the log transformation was applied, the data still violated
were corrected using covariance analysis (Curry Neuroimag- the assumption of normality and therefore non-parametric
ing Suite 7, Compumetics Ltd, Australia). Any epochs that analyses were conducted. Kruskal–Wallis tests were used to
still contained non-cerebral artefacts (> 75 µV) were identi- investigate group differences in mu suppression and related-
fied and removed from the analysis. Two participants were samples Wilcoxon signed rank tests were carried out to
removed from the analysis (one participant from the high investigate task-related changes in mu suppression. Analyses
AQ group and one participant from the ASD group) because were carried out separately for both frequency bands.
62.5% or less of the epochs were valid for one or more of
the individual conditions (mentalizing videos, non-men- Eye‑Tracking Analysis
talizing videos, fixation crosses in the mentalizing block,
fixation crosses in the non-mentalizing block). Excluding The eye-tracking data were analysed using EyeLink Data-
these participants, only 5.6% of epochs were invalid across Viewer software (SR Research Ltd., Ontario, Canada). Three
all participants. Preliminary analyses were carried out on dynamic rectangular regions of interest (ROIs) were created
the EEG data in order to clarify that the number of epochs for each action video individually. These ROIs corresponded
that were excluded did not significantly differ between par- to the head of the actor, the actor’s hand and the poker chip
ticipant groups or experimental conditions. The numbers of (see Fig. 2). These three interest areas were chosen based
excluded epochs were not normally distributed even after a on eye-tracking data from a previous behavioural study
log transformation was applied so non-parametric analyses using the same stimuli (Cole et al. 2017). The total number
13
Fig. 2 The dynamic regions of interest (ROIs) used in the eye-track- Three dynamic ROIs corresponding to (1) The poker chip, (2) The
ing data analysis for one of the action videos are shown overlaid onto actor’s head and (3) The actor’s hand, were created for each of the
screenshots from a the start and b the end of that particular video. 120 videos individually
and total duration of fixations in each ROI during each task factors indicate more evidence for the alternative hypoth-
(mentalizing/non-mentalizing) were calculated for each par- esis and lower values suggest more evidence for the null
ticipant. ROIs were analysed separately as these data are hypothesis. Bayes factors lower than 1/3 are considered to
not independent (participants cannot fixate in more than reflect substantial evidence for the null hypothesis and Bayes
one ROI at once). The eye-tracking data were not normally factors higher than 3 indicate substantial evidence for the
distributed even after a log transformation was applied and alternative hypothesis (Dienes 2014).
therefore non-parametric analyses were conducted. Inde-
pendent-samples Kruskal–Wallis tests were used to investi-
gate group differences and related-samples Wilcoxon signed Results
rank tests examined differences between tasks for each ROI.
Psychological Tests
Additional Analyses
A one-way MANOVA identified that scores on all psycho-
For all analyses (behavioural, EMG, EEG and eye-tracking), logical tests (ADOS-2, AQ, EQ, TASIT and SRS-2) were
any significant task-related differences that were identified significantly different between groups (see Table 3). Post-
were investigated further by analysing the data collected hoc pairwise comparisons identified that all groups were
during the presentation of clumsy actions across the two significantly different from each other on the ADOS-2, AQ
tasks. Identical clumsy actions were shown during both the and SRS-2 measures (Bonferroni correction applied). The
mentalizing and non-mentalizing tasks. Analysing the data Bonferroni corrected multiple comparisons identified that
in this way eliminates the possibility that apparent effects of the high AQ and ASD groups did not significantly differ in
the task are due to differences in observed action kinematics. TASIT scores (p = 0.92, B = 0.51). EQ scores did not sig-
Due to the spectral nature of ASD, any significant group nificantly differ between low and high AQ groups (p = 0.08,
differences that were found were also examined across the B = 4.62), however, the Bayes factor indicated there was
continuum of autistic traits. A principal components analysis evidence for a difference in EQ score between low and high
(PCA) was performed on all the psychological test scores AQ groups. All other group comparisons were significant
in order to obtain a single score for each participant that (p < 0.001 except difference in AQ scores between high AQ
reflected the level of autistic traits that they displayed. Linear and ASD groups; p < 0.01, and TASIT scores between low
regression analyses were then used to examine whether the and high AQ groups; p = 0.02). In all cases, where significant
levels of autistic traits significantly predicted the outcome group differences were found, the ASD group had scores that
variables e.g. levels of mu suppression. These additional reflected the highest level of autistic traits and the low AQ
analyses were conducted to further support the relationships group had scores reflected the lowest level of autistic traits.
between the outcome variables and ASD. Principal component analysis (PCA) was conducted using
Bayes factors were also calculated for all non-significant the psychological test scores in order to obtain a single value
results to provide evidence for, or against, our hypotheses, for each participant that represented the level of autistic traits
irrespective of sample size (Dienes 2014). Bayes factors of that they displayed. The psychological test scores correlated
1 indicate equal amounts of evidence to support both the with each other (all rs > 0.35) meaning that they were suita-
null hypothesis and the alternative hypothesis, higher Bayes ble for PCA. The Kasier–Meyer–Olkin measure of sampling
13
accuracy was 0.84 (above 0.6), Barlett’s test of sphericity pression in the ASD group). [After applying a Bonferroni
was significant χ2(10) = 146.07, p < 0.001 and the commu- correction, the new significance threshold was p = 0.017
nalities were all above 0.7 which collectively supported the (0.05/3)]. There were no significant differences between
inclusion of all the psychological tests in the PCA. PCA with ASD and low AQ groups (p = 0.18, r = 0.37, B = 1.44) or the
varimax rotation was used. The initial eigenvalues from the between the low and high AQ groups (p = 1.00, r = − 0.10,
PCA analysis showed that one factor (with an eigenvalue of B = 0.46).
3.57) explained 71.36% of the variance in psychological test Mu suppression in the 8–10 Hz frequency band was
scores. No other factors had eigenvalues higher than Kaiser’s significantly different between groups during the non-
criterion of 1 and therefore only one factor was extracted. mentalizing task at F3 (H(2) = 10.10, p = 0.006) and FCZ
This factor was labelled ‘autistic traits’. (H(2) = 7.32, p = 0.03). Pairwise comparisons showed that
the high AQ group displayed significantly lower levels of mu
EEG Data suppression than the low AQ group at F3 (p = 0.01, r = 0.54).
No other group differences were significant once threshold
8–10 Hz significance values had been adjusted using the Bonferroni
correction (p = 0.02; see supplementary material). Linear
Group Differences There were significant differences regression analysis demonstrated that the level of autistic
in the levels of mu suppression in the 8–10 frequency traits that participants displayed was not a significant predic-
band between groups during the mentalizing task at F4 tor of the amount of mu suppression in 8–10 Hz band dur-
(H(2) = 6.21, p < 0.05). Additionally, linear regression anal- ing the non-mentalizing task at F3 [F(1,38) = 0.02, p = 0.90,
ysis demonstrated that the level of autistic traits that par- R2 < 0.001, B = 0.44] or FCZ [F(1,38) = 0.03, p = 0.86,
ticipants displayed significantly predicted the amount of mu R2 < 0.01, B = 0.35].There were no other significant group
suppression in 8–10 Hz band at F4 during the mentalizing differences in mu suppression in the 8–10 Hz frequency band
task [F(1,38) = 0.47, p = 0.04, R2 = 0.11; see Fig. 3]. Pair- (see Supplementary Material).
wise-comparisons with adjusted p values (using the Bonfer-
roni correction) are reported and demonstrate a borderline Task‑Related Differences Initial analyses identified that mu
significant difference between the high AQ group and the suppression in the 8–10 Hz band was significantly lower
ASD group (p = 0.05, r = 0.47; with lower levels of mu sup- during the mentalizing task than the non-mentalizing task
at F3 across all participants (T = 581, p = 0.02, r = 0.38).
However, when this apparent significant task-related differ-
ence in mu suppression was investigated using data from
the clumsy actions alone (in order to control for differences
in action kinematics), there was no significant difference in
mu suppression in the 8–10 Hz range at F3 between clumsy
actions shown in the mentalizing task compared to the non-
mentalizing task (T = 518, p = 0.15, r = 0.23, B = 0.23).
There were also no task-related differences in mu suppres-
sion in the 8–10 Hz band at FCZ (T = 501, p = 0.21, r = 0.20,
B = 0.22) or F4 (T = 495, p = 0.25, r = 0.18, B = 0.22).
10–12 Hz
There were no significant differences in mu suppression in

the 10–12 Hz frequency band between groups or across tasks
at any of the cortical sites (see Supplementary Material).
TMS Data
Fig. 3 The relationship between the level of autistic traits that partici- Across all participants, there was no significant difference
pants displayed and the level of mu suppression in the 8–10 Hz fre- in motor resonance values in the FDI muscle between the
quency range at F4. Levels of autistic traits significantly predicted the mentalizing and non-mentalizing tasks (F(1,32) = 0.30,
degree of mu suppression at F4; participants that exhibited higher lev-
p = 0.59, ηp2 < 0.01), there was no significant interaction
els of autistic traits showed lower levels of mu suppression (8–10 Hz)
at F4 [F(1,38) = 0.47, p = 0.04, R2 = 0.11]. The curved lines represent between participant group and the task (F(2,32) = 0.73,
95% confidence intervals p = 0.49, ηp2 = 0.04) and there were no significant group
13
differences in motor resonance values (F(2, 32) = 0.73,

p = 0.49, ηp2 = 0.04). Bayesian t-tests indicated there was
significant evidence against higher motor resonance val-
ues during the mentalizing task compared to the non-men-
talizing task (B = 0.29). Bayes factors indicated that there
was neither evidence for, nor against, group differences in
motor resonance values; between low and high AQ groups
(B = 0.83), between high AQ and ASD groups (B = 1.25) or
between low AQ and ASD groups (B = 1.29).
There were no significant task or group differences for the
ADM data (see Supplementary Material).
Eye‑Tracking
Across all participants, significantly more and longer fix-

ations were made in the hand and head ROIs during the
mentalizing task compared to the non-mentalizing task
[hand ROI: number: (T = 169, p < 0.001, r = − 0.52), dura-
tion: (T = 288, p = 0.03, r = − 0.33); head ROI: number:
(T = 271, p = 0.02, r = − 0.34), duration: (T = 344, p = 0.02, Fig. 4 The relationship between performance on the mentalizing
r = − 0.35)]. There was borderline significantly more fixa- task and the level of mu suppression in the 8–10 Hz frequency band
tions in the poker chip ROI during the mentalizing than the at F3. Mentalizing performance significantly predicted the degree
non-mentalizing task (T = 297, p = 0.05, r = 0.29). However, of mu suppression at F3; participants with superior mentalizing per-
formances also showed greater levels of mu suppression at F3 in the
there was no significant task-related difference in the total 8–10 Hz frequency band [F(1,38) = 5.64, p = 0.02, R2 = 0.13]. The
duration of fixations within the poker chip ROI (T = 431, curved lines represent 95% confidence intervals
p = 0.61, r = − 0.08, B = 0.66).
When the eye-tracking data from the clumsy actions were
analysed alone, all previously significant results (including performance on the non-mentalizing task [F(1,41) = 5.14,
the borderline significant difference) were still significant p = 0.03, R2 = 0.11]. There were no other significant rela-
except for the duration of fixations within the head ROI tionships between eye-tracking data and behavioural perfor-
(T = 344, p = 0.12, r = − 0.24, B = 0.97; see supplementary mance (see Supplementary Material).
material for all results).There were no significant group
differences in the eye-tracking data (see Supplementary Eye‑Tracking and EEG
Material).
Linear regression analyses found that the degree of mu sup-
Relationships Between Data from Different pression did not significantly predict fixation patterns for any
Techniques of the cortical sites (see Supplementary Material).
EEG and Behavioural Performance TMS and Other Measures
When investigating the relationship between EEG and Linear regression analyses found that motor resonance val-
behavioural performances, linear regression analysis found ues did not significantly predict behavioural performances or
that mu suppression in the 8–10 Hz frequency band at F3 levels of mu suppression in either task (see Supplementary
during the mentalizing task significantly predicted perfor- Material).
mance on this task across all participants [F(1,38) = 5.64,
p = 0.02, R2 = 0.13; see Fig. 4]. There were no other signifi-
cant relationships between the EEG data and behavioural Discussion
performance (see Supplementary Material).
This study aimed to investigate the possible association
Eye‑Tracking and Behavioural Performance between ASD and atypical MS activity when mentalizing, as
well as the relationship between MS activity and mentalizing
The total duration of fixations within the poker chip ROI performance. Both TMS-induced MEPs and mu suppression
during the non-mentalizing task significantly predicted (measured by EEG) were used as indices of MS activity. The
13
EEG data show that higher levels of autistic traits (across with ASD. However, the lack of a significant relationship
clinical and non-clinical populations) were associated with between MS activity and mentalizing performance may
lower levels of MS activation in the right hemisphere when be due to compensatory strategies that individuals with
mentalizing. These lower levels of MS activity in the right high levels of autistic traits have adopted in order to suc-
hemisphere were not associated with poorer mentalizing cessfully infer the intentions of others from action kin-
performances. In contrast, lower levels of MS activity in ematics, despite atypical disengagement of the right MS.
the left hemisphere were associated with poorer mentalizing All participants in this study were high-functioning adults
performance but not associated with the levels of autistic with IQ scores within the typical range (> 70). It is pos-
traits that participants displayed. The TMS data did not show sible that if younger or lower functioning individuals were
differences in MS activity between groups or a relationship recruited they may not have developed sufficient compen-
between MS activity and mentalizing performances. Con- satory mechanisms and a relationship between right mu
sequently, although our sample size is small, the EEG data suppression and mentalizing performance may have been
provide evidence for MS involvement in mentalizing and found. Therefore, although our EEG data provide evidence
reduced MS activity in adults with high levels of autistic against the broken mirror theory, the use of compensatory
traits. The different lateralisation of MS activity associated strategies as well as our small sample size may have con-
with task performance and MS activity associated with high tributed to the lack of a relationship between MS activa-
levels of autistic traits means our data do not provide evi- tion and mentalizing performance.
dence that atypical MS functioning underlies mentalizing In contrast to the right-lateralised EEG data, left-later-
difficulties associated with ASD. alised mu suppression was not related to levels of autistic
Across all participants, the level of autistic traits dis- traits but was positively associated with mentalizing perfor-
played significantly predicted levels of mu suppression in mance. Participants who exhibited superior performances
the 8–10 Hz frequency band at F4 during the mentalizing on the mentalizing task also displayed higher levels of mu
task (see Fig. 3). These data imply that high levels of autistic suppression in the 8–10 Hz frequency band at F3 during this
traits are associated with reduced MS activity in the right task. These data support the motor resonance (or motor sim-
hemisphere when mentalizing. Our results support previous ulation) theory (Decety and Grèzes 2006; Landmann et al.
fMRI studies which have found reduced MS activation in 2011; Uithol et al. 2011). This theory states that observed
adults with ASD during mentalizing tasks (Baron-Cohen actions are internally simulated in the observer’s own MS
et al. 1999; Hadjikhani et al. 2009; Holt et al. 2014; Kana in order to infer the internal states of the individuals per-
et al. 2014; Wicker et al. 2008). forming the actions. In our study, right-handed actions were
The lower levels of right mu suppression in individuals viewed and therefore internal simulation of these actions
with high levels of autistic traits during the mentalizing task would be predicted to result in particularly increased activa-
were not observed during the non-mentalizing task. These tion in left hemisphere motor areas (Aziz-Zadeh et al. 2002).
data suggest mentalizing induces atypical suppression of the The relationship found between MS activity and mentalizing
right MS in these adults. Mentalizing tasks reliably induce performance in our EEG data supports the notion that inter-
activation in a cortical system known as the ‘mentalizing nal simulation of observed hand actions by the contralateral
system’ (Ciaramidaro et al. 2014; de Lange et al. 2008; Lom- MS is an important process in order to successfully infer
bardo et al. 2010; Spunt et al. 2011; Van Overwalle and others intentions. This compliments previous fMRI and
Baetens 2009). Atypical connectivity between the mental- TMS studies that have shown higher left MS activation
izing system and the MS has previously been reported in when viewing social right-handed actions compared to those
ASD (Damarla et al. 2010; Fishman et al. 2014; Just et al. without social context (Becchio et al. 2012; Bucchioni et al.
2007, 2004; Kennedy and Courchesne 2008; Noonan et al. 2013; Enticott et al. 2013b) and the poorer mentalizing per-
2009; Shih et al. 2010). It is possible that the reduced right formances observed in patients with MS lesions (Besharati
MS activity we observed in adults with high levels of autis- et al. 2016; Dal Monte et al. 2014).
tic traits was the result of atypical connectivity between the Initial analyses of task-related differences in mu suppres-
mentalizing system and the MS when inferring the inten- sion suggested that left-lateralised MS activity was lower
tions of others from their actions. during the mentalizing task than the non-mentalizing task.
Although our EEG data suggest that MS activation in However, this task-related difference in MS activity was
the right hemisphere is reduced in adults with high levels eliminated when only identical (‘clumsy’) actions were ana-
of autistic traits when mentalizing, no significant rela- lysed across tasks. This implies that the apparent task-related
tionship was found between right-lateralised MS activity difference in MS activity in the left hemisphere was likely to
and mentalizing performance. Consequently, our data do be the product of differences in action kinematics between
not provide evidence that the atypical right MS activa- the videos shown across the mentalizing and non-mentaliz-
tion identified underlies mentalizing difficulties associated ing tasks. Determining the success of the successful actions
13
shown in the non-mentalizing task required processing the the mentalizing task (Enticott et al. 2013b), and reduced
actors’ hands returning to their side of the board without the task-related differences in motor resonance values in adults
poker chip. It is therefore likely that the successful actions with high levels of autistic traits (Enticott et al. 2012; Puzzo
were internally simulated for slightly longer periods of time et al. 2009; Théoret et al. 2005). TMS stimulation was
than the spiteful actions shown in the mentalizing task, applied to the left hemisphere meaning that motor resonance
resulting in overall greater levels of MS activation during values reflected left MS activity. The lack of a relationship
the non-mentalizing task. between autistic traits and motor resonance values as well
Our EEG data show differences in mu suppression in as no task-related difference in motor resonance values com-
the 8–10 Hz frequency band rather than the 10–12 Hz fre- plement our left-lateralised EEG data, when differences in
quency band were associated with autistic traits and men- action kinematics were controlled for. However, our TMS
talizing performance. No significant relationships were data did not replicate the relationship found between left MS
found between mu suppression in the 10–12 Hz frequency activation and mentalizing performance in the EEG data.
band and any other measures. These data support previous A possible reason for the inconsistency between the TMS
EEG studies which have found mu suppression in the lower data and the EEG data is that these methods measure differ-
alpha frequency band (8–10 Hz) but not the higher alpha ent aspects of MS functioning. Across all participants, motor
frequency band during action observation (Cochin 1999; resonance values did not significantly predict the degree of
Simon and Mukamel 2016). These EEG data also support mu suppression (see Supplementary Material) supporting
the functional segregation of mu rhythm into two discrete previous studies (Andrews et al. 2015; Lepage et al. 2008).
sub-bands, complimenting previous work that found dis- Results from both MEG studies (Cheyne et al. 2003; Jones
tinct mu responses in low and high alpha bands (Dumas et al. 2009) and a combined MRI-EEG study (Arnstein et al.
et al. 2014; Frenkel-Toledo et al. 2014; Neuper et al. 2009; 2011) suggest that mu rhythms correspond to activation in
Pfurtscheller et al. 2000). The majority of previous studies S1. Although S1 is not considered to be a ‘core region’ of
investigating mu rhythm in individuals with ASD have not the MS, S1 has been reliably shown to display mirror prop-
split mu rhythm into sub-bands (Raphael Bernier et al. 2013; erties (Confalonieri et al. 2012; Gazzola and Keysers 2009;
Dumas et al. 2014; Fan et al. 2010; Oberman et al. 2005, Molenberghs et al. 2012; Porro et al. 1996). TMS on the
2008; Raymaekers et al. 2009). A previous EEG study that other hand, is very unlikely to cause MEPs in muscles of
did investigate mu suppression in two discrete sub-bands the hand through means other than the stimulation of M1
in adults with ASD found reduced mu suppression in the (Lepage et al. 2008). TMS-induced MEPs measured dur-
11–13 Hz frequency band when passively observing hand ing action observation are thought to measure increased
actions and no atypicalities in the 8–10 Hz frequency band excitability in M1 as the result of excitatory cortico-cortical
(Dumas et al. 2014). Similar to this previous study, our data connections from prefrontal MS areas (IFG/vPMC; Fadiga
show no atypicalities in mu suppression in the 8–10 Hz et al. 2005; Loporto et al. 2011). Therefore, if mu suppres-
range in adults with ASD when performing a non-mentaliz- sion measured by EEG reflects MS activity in S1 and TMS-
ing task. The reduced mu suppression in the upper sub-band induced MEPs provide an index of prefrontal MS activity
during passive action observation in the previous study may then this could explain the differences between the results
be the result of the slightly higher frequency band used. This from these two measures.
frequency band encroaches into the beta frequency range An alternative reason for the inconsistency between the
12(/13)-30(/35)Hz (Haenschel et al. 2000; Kilavik et al. EEG and TMS data could be due to the differences in the
2013; Miller 2007). Similar to mu suppression, oscillatory spatial and temporal properties of these two measurements
activity in the beta frequency range is suppressed when of MS activity. The EEG measurements in this study reflect
observing biological motion (Babiloni et al. 2002; Milston the sum of post-synaptic neuronal activity over a large corti-
et al. 2013; Perry et al. 2010) and atypical oscillatory activ- cal area and a relatively long time period (throughout video
ity in the beta frequency range has previously been reported or fixation cross display) whereas TMS measures brief
in adults with ASD (Cooper et al. 2013; Honaga et al. 2010). induced increases in corticospinal activity from peripheral
In summary, mu suppression in the 8–10 Hz frequency sub- muscles, induced by stimulating a relatively small popula-
band (and not 10–12 Hz) appears to reflect MS activity in the tion of neurons at a discrete time point (Andrews et al. 2015;
left hemisphere that is related to mentalizing performance, Pineda 2005; Rossini et al. 1994). Therefore, the EEG and
and MS activity in the right hemisphere is reduced in adults TMS datamay differ due to differences in the spatial and
with high levels of autistic traits when mentalizing. temporal properties of the measurements.
The TMS data show no relationship between motor reso- The total duration of fixations in the poker chip ROI pre-
nance values and either mentalizing performance or autistic dicted non-mentalizing task performance but there were no
traits and no differences in motor resonance values across significant relationships between any of the eye-tracking
tasks. We had expected larger motor resonance values during measures and mentalizing performance. This implies that
13
the visual information within the poker chip ROI was vital reduced mu suppression. The investigation of individual
for performance on the non-mentalizing task; this is to be and within group variability in mu suppression is beyond
expected as performances relied upon identifying whether the scope of this study but could be an interesting avenue
the poker chip was successfully passed to another player for future research. Although a significant relationship was
or was dropped before being passed to another player. In found between autistic traits and right-lateralised mu sup-
contrast, during the mentalizing task, the final location of pression (8–10 Hz), significant group differences were not
the poker chip was always the same (all actions were unsuc- observed. Examining neural differences in terms of the
cessful) but participants were required to infer the intentions continuous measure of autistic traits may have been a more
of the actors from their action kinematics. The lack of any sensitive measure than examining group differences due to
significant relationships between the eye-tracking data and within group variability in autistic traits, and therefore neu-
mentalizing performance suggests that participants did not ral measures, may have reduced chances of observing group
have a rigid method in which they did this. This is supported differences. The inclusion of medicated participants in this
by the greater number of fixations made during the mental- study may have also influenced the data; six participants
izing task compared to the non-mentalizing task, suggesting in the ASD group were taking psychotropic medications
a greater degree of re-diverting attention, perhaps reflecting which have been shown to increase corticospinal excitabil-
an increased level of uncertainty regarding where to direct ity (Gilbert et al. 2006; Minelli et al. 2010). Due to the high
their visual attention. comorbidity of ADHD, depression and anxiety in ASD, the
There were no significant differences in the eye-tracking inclusion of adults taking psychotropic medication is com-
data associated with high levels of autistic traits during the mon in TMS studies with ASD participants (Enticott et al.
mentalizing task. This means that the lower levels of MS 2010, 2013a; Oberman et al. 2014). Despite the possible
activity during the mentalizing task exhibited by adults with influence of psychotropic medication on corticospinal excit-
high levels of autistic traits were not due to reduced fixation ability, our TMS data show no group differences in resting
on the observed action kinematics in these individuals. motor thresholds and there was no significant difference
There are a number of limitations associated with this in resting motor threshold values between medicated and
study including the small sample size, particularly for the non-medicated participants (see Supplementary Material).
TMS data, which may have resulted in limited power to Despite these limitations, our EEG data add to the existing
detect differences in MS functioning associated with ASD. literature by identifying lower levels of right MS activity
The particularly small sample size for the TMS data was in adults with high levels of autistic traits when inferring
due to a number of participants (n = 6) not being able to the intentions of others from their actions and higher lev-
complete the TMS element of this study either due to not els of left MS activity associated with superior mentalizing
tolerating stimulation or having particularly high motor performances. These EEG data suggest that the MS has a
thresholds. This particularly small sample size may have role in inferring the intentions of others from their actions,
contributed to the lack of differences in motor resonance providing support for the motor resonance theory of social
values found both across tasks and between groups. The lack cognition (Agnew et al. 2007; Landmann et al. 2011; Les-
of significant mentalizing deficits in adults with high levels lie et al. 2004; Rizzolatti et al. 2002). Additionally, adults
of autistic traits in our study may have also limited our abil- with high levels of autistic traits appear to display atypical
ity to detect a relationship between motor resonance values top-down suppression from the mentalizing system to the
and autistic traits; participants with higher levels of autistic MS in the right hemisphere when inferring the intentions of
traits and significant mentalizing deficits were recruited then others. Therefore, this study provides evidence for reduced
a significant relationship may have been observed. However, MS activity in adults with high levels of autistic traits when
previous studies have also reported typical motor resonance mentalizing and a potential role of the MS in inferring the
values in adults with ASD (Enticott et al. 2013b; Kirkovski intentions of others.
et al. 2016) and the lower levels of mu suppression found
in our study suggest MS atypicalities were detectable in Acknowledgments Eleanor Cole was funded by an Economic Social
Research Council (ESRC) 1+3 Ph.D. studentship. We thank Michael
our participant sample regardless of typical behavioural Barham for his help with out of hours data collection as well as Sou
performances. Bekkali, Charlotte Davies, Claire McNeel, Daniel Corp and Melissa
It is possible that mu suppression variability was higher Kirkovski for their support during data collection and all the partici-
both between participants and within individuals with high pants for their contributions.
levels of autistic traits compared to those with low levels
Author contributions EJC designed the experiment, collected and
of autistic traits. Therefore, the reduced levels of right mu analysed the data, wrote the first draft of the manuscript, edited the
suppression observed in individuals with high levels of manuscript, and approved the final version. NEB helped design the
autistic traits when mentalizing may reflect intermittent experiment, edited the manuscript and approved the final version. PGE
displays of typical mu suppression rather than consistently assisted with the experimental design, constructing the experimental
13
set-up, guided the analysing of the data, edited the manuscript and Psychiatry, and Allied Disciplines, 38(7), 813–822. https://
approved the final version of the manuscript. doi.org/10.1111/j.1469-7610.1997.tb01599.x.
Baron-Cohen, S., Ring, H. A., Wheelwright, S., Bullmore, E. T.,
Brammer, M. J., Simmons, A., & Williams, S. C. R. (1999).
Compliance with Ethical Standards Social intelligence in the normal and autistic brain: An fMRI
study. European Journal of Neuroscience, 11(6), 1891–1898.
Conflict of interest The authors declare that they have no conflict of Baron-Cohen, S., Wheelwright, S., Skinner, R., Martin, J., & Clubley,
interest. E. (2001). The autism-spectrum quotient (AQ): Evidence from
Asperger syndrome/high-functioning autism, males and females,
Open Access This article is distributed under the terms of the Crea- scientists and mathematicians. Journal of Autism and Develop-
tive Commons Attribution 4.0 International License (http://creativeco mental Disorders, 31(1), 5–17. https://doi.org/10.1023/A:10056
mmons.org/licenses/by/4.0/), which permits unrestricted use, distribu- 53411471.
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Journal of Autism and Developmental Disorders

Investigating Mirror System (MS) Activity in Adults with ASD When

© The Author(s) 2018. This article is an open access publication

Introduction of autistic traits. Individuals without an ASD diagnosis but

Table 1 Demographic Low AQ High AQ ASD p ηp2

p values were obtained from one-way MANOVA unless otherwise stated

There were no significant differences in mu suppression in

differences in motor resonance values (F(2, 32) = 0.73,

Across all participants, significantly more and longer fix-

EEG and Behavioural Performance TMS and Other Measures

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