Infant neural sensitivity to dynamic eye gaze is associated with later emerging autism.
ABSTRACT Autism spectrum disorders (henceforth autism) are diagnosed in around 1% of the population . Familial liability confers risk for a broad spectrum of difficulties including the broader autism phenotype (BAP) [2, 3]. There are currently no reliable predictors of autism in infancy, but characteristic behaviors emerge during the second year, enabling diagnosis after this age [4, 5]. Because indicators of brain functioning may be sensitive predictors, and atypical eye contact is characteristic of the syndrome [6-9] and the BAP [10, 11], we examined whether neural sensitivity to eye gaze during infancy is associated with later autism outcomes [12, 13]. We undertook a prospective longitudinal study of infants with and without familial risk for autism. At 6-10 months, we recorded infants' event-related potentials (ERPs) in response to viewing faces with eye gaze directed toward versus away from the infant . Longitudinal analyses showed that characteristics of ERP components evoked in response to dynamic eye gaze shifts during infancy were associated with autism diagnosed at 36 months. ERP responses to eye gaze may help characterize developmental processes that lead to later emerging autism. Findings also elucidate the mechanisms driving the development of the social brain in infancy.
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ABSTRACT: Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex-and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35–46%) of patients), as well as the deficit in melatonin (51% (45–57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41–54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS–melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS–melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD. Translational Psychiatry (2014) 4, e●●; doi:10.1038/tp.2014.120; published online xx xxx 2014 INTRODUCTION Autism spectrum disorders (ASDs) are complex, heterogeneous and multifactorial disorders characterized by impaired social communication and repetitive/stereotyped behaviors. The diag-nosis of ASD currently relies entirely on patient clinical evaluation.Translational psychiatry. 10/2014; 4.
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ABSTRACT: Background: Autism is known to be associated with hyperserotoninemia and, more recently, with decreased blood melatonin level. Melatonin is a neurohormone synthesized from serotonin and involved in circadian rhythms and sleep regulations. Thus, serotonin and melatonin are two ends of a biochemical pathway, and little is known concerning all the steps of this pathway in patients with Autism Spectrum Disorders. Moreover, the clinical relevance of these biochemical endophenotypes remains to be determined. Objectives: Here we explore the serotonin-melatonin pathway in a large cohort of patients with ASD, in order to (i) better characterize the biochemical abnormalities of this pathway in ASD, (ii) determine the clinical correlates of these biochemical abnormalities, and (iii) assess the relevance of these biochemical parameters as biomarkers for ASD diagnosis. Methods: The five parameters related to the serotonin-melatonin pathway, i.e. serotonin, arylalkylamine N-acetyltransferase (AA-NAT) enzyme activity, N-acetylserotonin, acetylserotonin methyltransferase (ASMT) enzyme activity, and melatonin, were measured in the blood of 203 patients with ASD, their unaffected relatives (291 parents and 92 sibs), and age- and sex-matched controls. Biochemical data were correlated with clinical data obtained from ADI-R for 117 patients. Results: Patients with ASD display elevated blood serotonin and N-acetylserotonin levels (p<0,001) compared to controls and unaffected relatives, and decreased ASMT activity and melatonin levels (p<0,001) compared to controls. When confronted to clinical data, melatonin deficiency appears significantly associated with stereotyped behavior (ADI-R axis D, p=0,003). Finally, comparisons between ASD patients, controls and unaffected sibs on the one hand, and between autism and Asperger syndrome on the other hand, reveal that hyperserotoninemia is a relevant biomarker of autism, with good specificity and sensitivity. Conclusions: This study confirms the previously reported major abnormalities of the serotonin-melatonin pathway in ASD. The typical biochemical profile of ASD patients suggests a deficit of the ASMT enzyme, consistent with our previous work. Serotonin and melatonin are both clinically relevant parameters, serotonin as a specific biomarker of autism, and melatonin for behavioral correlates. These results highlight the clinical interest of the serotonin –melatonin pathway in ASD, and its potential role as a susceptibility factor to autism.International Meeting for Autism Research 2010; 05/2010
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ABSTRACT: It has been previously reported that structural and functional brain connectivity in individuals with autism spectrum disorders (ASD) is atypical and may vary with age. However, to date, no measures of functional connectivity measured within the first 2 years have specifically associated with a later ASD diagnosis.Journal of Neurodevelopmental Disorders 01/2014; 6(1):40. · 3.71 Impact Factor
Current Biology 22, 338–342, February 21, 2012 ª2012 Elsevier Ltd All rights reservedDOI 10.1016/j.cub.2011.12.056
Infant Neural Sensitivity
to Dynamic Eye Gaze Is Associated
with Later Emerging Autism
Mayada Elsabbagh,1,2,* Evelyne Mercure,1Kristelle Hudry,3
Susie Chandler,4Greg Pasco,4Tony Charman,4
Andrew Pickles,5Simon Baron-Cohen,6Patrick Bolton,5
Mark H. Johnson,1,* and the BASIS Team7
1Centre for Brain and Cognitive Development, Birkbeck
College, University of London, London WC1E 7HX, UK
2Department of Psychiatry, McGill University, Montreal,
Quebec H3A 1A1, Canada
3Olga Tennison Autism Research Centre, School of
Psychological Science, La Trobe University, Bundoora,
Victoria 3086, Australia
4Centre for Research in Autism and Education, Institute of
Education, University of London, London WC1H 0AL, UK
5Institute of Psychiatry, King’s College London,
London SE5 8AF, UK
6Autism Research Centre, University of Cambridge,
Cambridge CB2 8AH, UK
Autism spectrum disorders (henceforth autism) are diag-
nosed in around 1% of the population . Familial liability
confers risk for a broad spectrum of difficulties including
the broader autism phenotype (BAP) [2, 3]. There are cur-
rently no reliable predictors of autism in infancy, but charac-
teristic behaviors emerge during the second year, enabling
diagnosis after this age [4, 5]. Because indicators of brain
functioning may be sensitive predictors, and atypical eye
contact is characteristic of the syndrome [6–9] and the
BAP [10, 11], we examined whether neural sensitivity to
eye gaze during infancy is associated with later autism
outcomes [12, 13]. We undertook a prospective longitudinal
study of infants with and without familial risk for autism. At
6–10 months, we recorded infants’ event-related potentials
(ERPs) in response to viewing faces with eye gaze directed
toward versus away from the infant . Longitudinal
analyses showed that characteristics of ERP components
evoked in response to dynamic eye gaze shifts during in-
fancy were associated with autism diagnosed at 36 months.
ERP responses to eye gaze may help characterize develop-
mental processes that lead to later emerging autism. Find-
of the social brain in infancy.
Results and Discussion
In the present study, we ascertained whether measurements
of specific brain function might be sensitive predictors of
later outcomes in infants at familial risk for autism spectrum
tive impairments in social skills and communication and the
presence of rigid, stereotyped, and repetitive behaviors. We
tested the hypothesis that atypical neural responses to eye
gaze in infants at familial risk for autism relate to emerging
symptoms of autism assessed behaviorally at 3 years of age.
We followed up a group of 104 infants: 54 at risk for autism
and 50 control infants who had no family history of autism
from the age of 6–10 months and through to 36 months.
At 6–10 months of age, we recorded infants’ event-related
potentials (ERPs) using a 128-channel hydrocel infant net, in
response to dynamic gaze shifts toward versus away from
the infant (Figure 1). In addition to this primary contrast, we
also examined the extent to which any observed patterns
suring ERPs in response to (1) the first static presentations of
faces appearing in the gaze-shift sequence displaying direct
versus averted gaze (previously used in our preliminary study,
) and (2) face versus visual noise (the latter was con-
structed from the same face stimuli, with randomization of
the phase spectra while keeping constant the amplitude
and color spectra ). We measured characteristics of three
infant components, time-locked to the onset of stimulus pre-
sentation. The P1, N290, and the P400 components, quantified
by their amplitude or latency, are modulated in a number
of face-perception tasks, including tests of sensitivity to the
direction of eye gaze in infants as young as four months .
Relevant experimental findings from different laboratories,
including our own, have identified these ERP components in
infants as precursors of the well-established face-sensitive
N170 component in adults . In interpreting our results, we
did not discriminate between amplitude or latency changes,
because both measures equally reflect differences in the
neural response to the contrasts of interest.
We constrained our general linear model analyses (Figure 1,
detailed in Figure S1 and Table S1 available online) against
type 1 error in three ways. First, we tested hypothesis-driven
within-group effects only when higher order interactions were
significant (using Greenhouse-Geisser corrections; Table S1).
Second, we focused our primary analysis on the dynamic
ralistic shared attention contexts known to be disrupted in
autism [12, 13]. Furthermore, several ERP studies have sug-
gested that, relative to static face presentation, dynamic shifts
engage a wider range of social brain mechanisms [18, 19].
Finally, in view of our findings from our preliminary study ,
we were specifically interested in the P400 response relative
to the P1 and N290. Full results of other components and
contrasts are presented in Figure S1 and Table S1.
Face-Related ERPs Distinguish Infants at Risk from the
Our results generally replicated and extended previous
reports, differentiating infants at risk from controls with no
family history of autism [10, 20–22]. In the present study,
a significant risk group 3 condition interaction was observed
for the P400 response in response to dynamic gaze shifts
toward versus away from the infant. Notably, in the dynamic
gaze condition the control group, but not the group of infants
at risk, showed a significant difference in response to gaze
7A full list of the BASIS Team members may be found in the Acknowledg-
*Correspondence: email@example.com (M.E.), mark.johnson@
toward, compared to away from, the infant (Figure 1; within
group contrasts: control group p < 0.001; combined at-risk
group p = 0.48). However, these risk-group effects were not
restricted to dynamic gaze contrasts but appear to extend to
other face processing mechanisms, i.e., static direct vs.
averted gaze and face vs. noise (Figure S1; Table S1).
Overt behavioral signs of autism are rarely observable in the
cognitive and brain function measures can successfully differ-
entiate groups of infants at risk from low-risk control within the
first year of life . Consistent with our current findings, these
effects have been reported in visual processing  and in
flexibility of switching attention . Direct measurement of
brain activity has also revealed early risk-group differences
in response to face stimuli  and in sensitivity to the direc-
tion of eye gaze . Our findings, from a larger sample than
those reported previously, verified that such group effects
are observable within the first year of life, across both face
and gaze processing mechanisms. Within this early period,
risk for autism appears to confer a range of differences in the
Infant Brain Response to Dynamic Gaze Is Associated with
Autism at 36 Months
In order to determine how these infancy findings are associ-
ated with later behavioral outcomes, an independent team
conducted clinical research assessments of the same infants
when they reached 24 months and 36 months of age, with an
outcome diagnosis of Autism spectrum disorders (ASD) at
36 months for 17 toddlers from the at-risk group. Testing the
relationship between infant brain function measures and later
outcomes followed on from the previous analysis based on
Figure 1. Association between Infant ERPs in Response to Eye Gaze and Autism Outcomes
(A) Participating families first visited the lab when their infants were 6–10 months of age. Electrophysiological recording was done during this visit. Infants
were prepared for the EEG session.
(B) Electrophysiological response to gaze shifts over occipitotemporal channels.
(C) Around 2 and 3 years of age, the same infants were tested by an independent team using several measures including the ADOS, a semistructured obser-
vational measure of autism-related characteristics. Based on information from all visits, combined with expert clinical judgment, infants in the at-risk group
were classified as having ASD or not.
(D) Controlling for age at the first visit, significant condition 3 risk-group interactions were observed for the amplitude of the P400 [F(1,92) = 6.7, p = 0.01];
planned post hoc tests focused on within-group difference between response to direct versus averted gaze controlling for age at baseline and develop-
mental level at 36 months. Estimated mean differences between responses to gaze toward versus away are displayed for each group (standard error
bars are displayed). Findings suggest that differentiation between gaze toward versus away was reliable in the both the control group (p < 0.001) and
the at-risk without ASD group (p = 0.04). By contrast, the at-risk group that developed ASD showed no differentiation (p = 0.67) nor did the subgroup
that developed early and persistent symptoms (p = 0.27). Findings from static face and face versus noise contrasts are presented in Figure S1 and Table S1.
Infant Neural Sensitivity Associated with Autism
risk groups but involved splitting the at-risk group based on
their outcomes (control, at-risk ASD, at-risk no ASD). Post
hoc tests focused on within group differences controlling for
overall developmental level to ensure specificity of any
observed effects to the diagnostic group. The focus on
within-group differences ensured that any unexpected global
differences in baseline electroencephalography (EEG) would
not drive results of the ERP post hoc tests. As infants, the
control group, as well as the at-risk group with no ASD,
showed a higher P400 amplitude for gaze shifts away versus
toward, whereas the ASD group did not differentiate the two
conditions (Figure 1D). The face versus noise contrast did
not distinguish the at-risk ASD group from the two other
groups, suggesting some degree of specificity of the effect
to dynamic gaze-shift condition (Figure S1, Table S1).
Given variability in developmental pathways leading to diag-
nosis at 3 years, we were interested in examining whether
these early brain differences may relate more specifically to
social and communication impairment emerging during the
second year and then persisting into the third year (‘‘early
and persistent ASD’’). This question is also important in view
of previous studies on typical development suggesting that
infant sensitivity to eye gaze relates to social and communica-
tion skills emerging around the second birthday. Those skills
were assessed at 2 and 3 years of age using the Autism Diag-
nostic Observation Schedule (ADOS; Figure 1C; ). Around
60% of infants in the ASD group exhibited clear symptoms
when assessed at the age of two, meeting ADOS clinical cutoff
at that age. We examined the P400 response to gaze shift
infants who did not meet ADOS clinical cut-off criteria at the
age of 2, leaving nine infants in the ‘‘early and persistent
ASD’’ sample. The same lack of differentiation between gaze
toward and away was observed in this subgroup (p = 0.27).
Moreover, the early and persistent subgroup also showed
differences in other gaze-related ERP components, namely
the P1 and N290 (Figure S1; Table S1). This finding suggests
that ERP responses to dynamic gaze shifts may help charac-
terize distinct developmental profiles leading to autism.
Neither static gaze nor face versus noise contrasts reliably
distinguished the ASD group from the two other groups.
Notwithstanding this pattern, findings from the static gaze
condition (Figure S1), suggest that latency of the P400 in
response to direct versus averted gaze did not differ in the
control group (p = 0.89) or at-risk group who developed ASD
(p = 0.54), but that within the at-risk group who did not develop
ASD the response to direct gaze was slower than to averted
gaze (p = 0.007). Given the heterogeneity of outcomes in the
group that did not develop autism, we further verified that
this within-group difference was not driven by those infants
who had other forms of developmental concerns not meeting
clinical thresholds for an autism diagnosis. We confirmed
that the effect was primarily driven by those infants at risk
who were found to be developmentally typical at 3 years of
age (p = 0.04) and less reliably in the group with other develop-
mental concerns (p = 0.09). This pattern suggests that at least
some risk-group differences may be driven by infants who do
not go on to develop autism in toddlerhood.
Are Brain Function Effects Driven by Differences in
It has been frequently suggested that individuals with autism
 and their nonaffected relatives  exhibit differences in
the scanning of faces and social scenes. Such putative
scanning differences in the period of infancy may explain or
modulate the neural response to eye gaze observed in our
study. However, in general, evidence from infants at risk has
thus far indicated typical patterns of scanning of social scenes
within the first year of life, supporting the view that atypical
scanning emerges over the early developmental period .
In fact, one study reported that normative face-scanning pat-
terns modulate later language outcomes in both infants at risk
in the current study. Among a number of different methodolog-
imental Procedures), we used a separate eye tracking task to
examine the amount of time spent looking at the eye region of
the face. This allowed us to assess whether the differences
arising in the neural response to eye gaze could be attributed
to decreased scanning of, or attention to, the eye region.
Eye-tracking data from 93 of the 104 infants were retained
for analysis if at least 1.5 s of looking time were accumulated
across one or both trials. Rectangular Areas of Interest
(AOIs) were defined around the eye region, the mouth region,
and other areas covering the remaining non-face regions. No
differences were observed across the risk-groups or based
on outcome groups in the percentage of time spent fixating
on the models’ eyes relative to other regions (Table 1). These
findings confirm that brain function differences observed in
the group of infants at risk are not driven by overt differences
in visual scanning of social scenes. These findings are consis-
tent with the emerging body of evidence suggesting that the
expression of risk for autism within the first year is subtle
when measured using overt behavioral markers .
Ontogeny of Autism and Its Broader Phenotype
Typical infants’ sensitivity to eye gaze in the first year of life is
a precursor to a range of social-communicative skills that
emerge as early as 18 months. Very early sensitivity to eye
gaze [26, 27] develops rapidly and takes on the more sophisti-
cated form of joint attention, where the infant shares the
adult’s focus of interest. The infant can then use this social
context to develop a wide array of skills (e.g., to learn words,
interpret facial expressions, and understand intentions). This
evidence has led to the proposition that, in autism, disruptions
in the early instantiation of brain networks underlying social
perception, results in decreased attention to, or reduced in-
terest in, the social world [12, 13]. This early perturbation,
potentially affecting sensitivity to eye gaze, interferes with
the emergence of typical developmental milestones. The
Table 1. Supporting Eye-Tracking Task
meanSD meanSD meanSD
9.43.3 3.33.2 3.0
Control versus at-risk = 0.14
Control versus at-risk = 0.21
20.3 72.2 23.174.7
No ASD versus ASD = 0.34
No ASD versus ASD = 0.39
17 16.420.7 21.3
Thistableshows number of infants, average amount of lookingtime oneach
trial, and distribution of gaze across different areas of interest. P values
yielded from the pairwise comparison of risk group or outcome subgroup
Current Biology Vol 22 No 4
cascading effects eventually derail the development of social
Although converging evidence from behavioral [6, 7] and
neuroimaging [8, 9] studies supports the notion that atypical
sensitivity to eye gaze is characteristic of individuals with
autism and their unaffected relatives , our study is the first
to formally test the aforementioned developmental account.
Our findings, however, suggest that atypical brain function
symptoms. Although overt behavioral signs of autism are
rarely observable in the first year, response to dynamic gaze
shifts during the first year of life distinguished the group of
infants who later developed autism. The same pattern of find-
(face versus visual noise stimuli), suggesting at least some
degree of effect specificity. This pattern is consistent with
the view that whereas sensitivity to static gaze information
emerges early in development, dynamic gaze shifts are likely
to engage multiple bottom-up and top-down social brain
networks, including those concerned with prediction of future
events . Thus, the dynamic nature of our gaze-shift stimuli
involving rapid changes may be a critical feature of the task we
used, and future research needs to determine in more detail
the specificity or otherwise of these effects to eye gaze.
Our findings, from a larger sample than those reported previ-
ously, also verified thatrisk group effects areobservable within
anisms. Within this early period, risk for autism appears to
confer a range of differences in the developing brain. Future
work will also be required to ascertain why the secondary stim-
visual noise) revealed risk-group differences that were not due
One possibility is that early brain function differences reflect
early manifestations of the broader autism phenotype that will
become more clearly evident in behavior later in life. Another
possibility is that at least some early differences may reflect
protective factors or mechanisms of brain adaptation in those
infants at risk who go on to exhibit a typical behavioral reper-
inary evidence in the current study related to the response to
of individuals diagnosed with autism [29, 30].
Taken together, our findings potentially allow for the early
identification of those infant siblings who are at highest risk
for developing later impairments, paving the way for the
more selective targeting of early intervention efforts and pro-
cedures. In the future, more reliable diagnostic and, more im-
portantly, prognostic indicators of the condition may become
clear through a better understanding of the way in which very
early differences in thebrain functioning of infants atrisk relate
to variable developmental pathways . Previous attempts to
draw conclusions regarding clinical utility of laboratory mea-
sures in adults and infants alike have demonstrated the need
for caution , not least because although group mean differ-
ences emerge, there is still considerable overlap between
groups in individual infant responses. Whereas clinical utility
can only be established using much larger and unselected
regarding the correspondence between infant early laboratory
measures and later clinical outcomes. More robust prediction
of clinical diagnosis may require a combination of a number of
risk and protective factors, including response to gaze.
Participants and Clinical Characterization
Recruitment, ethical approval (UK NationalHealth Service National Research
Ethics Service London REC 08/H0718/76), and informed consent, as well as
orative network facilitating research with infants at risk for autism (www.
basisnetwork.org). Families enroll from various regions when their babies
are younger than 5 months of age, and they are invited to attend multiple
research visits until their children reach 3 years of age or beyond. Each visit
lasts a day or two and is adapted to meet the families’ needs. Measures
collected are anonymizedand shared among scientists to maximizecollabo-
senior consultants works closely together with the research team(s) and, if
about the child arising during the study are adequately addressed.
One hundred and four infants from BASIS (independent from the pilot
group ) took part in the current study (54 at risk, and 50 control).
Twenty-one of the at-risk infants were male and 33 were female. Twenty-
one of the low-risk infants were male and 29 were female.Along with several
other measures, the infants were seen for the ERP task at the Centre for
Brain and Cognitive Development when they were 6–10 months of age
(mean = 238.3 days, SD = 37.2). Subsequently, 52 (from 54) of those at
risk for ASD were seen for assessment around the second birthday
(mean = 23.9 months, SD = 1.2) and 53 around their third birthday (mean =
37.7 months, SD = 3.0), by an independent team at the Centre for Research
in Autism and Education, Institute of Education.
During the 36 month visit, a battery of clinical research measures was
administered including the Autism Diagnostic Observation Schedule and
the Autism Diagnostic Interview. Consensus ICD-10 criteria were used to
ascertain diagnosis in a subgroup of infants at risk using all available infor-
mation from all visits by experienced researchers (T.C., K.H., S.C., G.P). The
Supplemental Experimental Procedures present detailed participant char-
acteristics including ascertainment of risk status, background measures
at each visit, and outcome characterization including clinical classification.
ERP Task at 6–10 Months
In our previously published preliminary work , we investigated group
differences between infants at risk for autism and low-risk controls, aged
10 months in their response to static direct versus averted gaze (for details
on the pilot study see Supplemental Experimental Procedures). For the
current study, a modified ERP task was administered during the first visit.
The infants sat on their parents’ laps at a 60 cm distance from a 40 3
29 cm computer screen. Gaze during stimulus presentation was recorded
by video camera. Each trial block began with a static colorful fixation stim-
ulus followed by a color image of one of four female faces, with gaze
of the same block, the face remained on the screen but displayed three to
six gaze shifts, alternating from directed toward to away from the infant.
Faces were aligned with the center of the screen with the eyes appearing
at the same location as the fixation stimuli, to ensure that infants were
fixating the eye region. The faces subtended 21 3 14 degrees of visual
angle. In addition to face trial blocks, during approximately one third of all
blocks, infants were presented with ‘‘visual noise’’ stimuli. The latter were
constructed from the same faces presented within the task, by randomizing
the phase spectra while keeping the amplitude and color spectra constant
. Fixation stimuli, preceding the onset of the face and noise stimuli,
subtended approximately 1.6 3 1.6 degrees and were presented for a vari-
able duration of 800 to 1,200 ms. Each trial lasted for 1,000 ms.
A 128 channel Hydrocel Sensor Net was mounted on each infant’s head,
while they were seated on the parent’s lap in front of the stimulus screen.
When the infant was attending toward the screen, trials were presented
continuously for as long as the infant remained attentive, with brain electri-
cal activity measured simultaneously using the vertex as a reference (Cz in
the conventional 10/20 system). EGI NetAmps 200 was used (gain = 1,000).
Data were digitized with a sampling rate of 500 Hz and band-pass filtered
between 0.1–100 Hz. Subsequent to artifact rejection, ERPs were ascer-
tained based on visual inspection of grand averages (detailed in Supple-
mental Experimental Procedures).
Supporting Eye-Tracking Task at 6–10 Months
During their first visit, infants were administered a battery of eye-tracking
tasks several hours before the ERP task was undertaken and containing
Infant Neural Sensitivity Associated with Autism
tion in which infants were presented with videos of female faces displaying
gaze shifts toward or away from the infant. Looking behavior was recorded
with a Tobii eye tracker. The Tobii system has an infrared light source and
a camera mounted below a 17 inch flat-screen monitor to record corneal
reflection data. Gaze direction of each eye is measured separately, and
from these measurements, the Tobii system evaluates where on the screen
the individual is looking. During the task, the infant was seated on the
parent’s lap, at 50–55 cm from the Tobii screen, with height and distance
of the screen adjusted to obtain good tracking of the eyes. A five-point
calibration sequence was run, and recording and presentation of the study
stimuli only started when at least four calibration points were marked as
properly attuned to each eye. Gaze data were recorded at 50 Hz.
faces. Each began with an animated fixation stimulus attracting the infant’s
attention to the center of the screen. Once fixated, a still face was presented
for 5 s. Subsequently, the model shifted her gaze away from the infant
and then alternated gaze shifts back toward and again away from the
infant (turning left or right in pseudorandom order) for a maximum of ten
Supplemental Information includes three figures, three tables, and Supple-
mental Experimental Procedures and can be found with this article online at
We are very grateful for the enormous contributions the BASIS families have
made toward this study. The research is supported by the UK Medical
Research Council (G0701484) and the BASIS funding consortium led by
Autistica (www.basisnetwork.org) to M.H.J. and a Leverhulme Early Career
Fellowship to M.E. Further support for some of the authors is from COST
(European Cooperation in Science and Technology) action BM1004. The
Fernandes, Holly Garwood, Teodora Gliga, Leslie Tucker, and Agnes Volein.
Received: November 23, 2011
Revised: December 29, 2011
Accepted: December 29, 2011
Published online: January 26, 2012
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Current Biology Vol 22 No 4