Dissociating Neural Response to Gaze Cues in ASD and Schizophrenia
using Simulated Face-to-Face Interaction
J Foss-Feig, A Naples, E Levy, R Tillman, H Reuman, K Law, N Santamauro, C Diehl, C Schleifer, V Srihari, A Anticevic & J McPartland
McPartland Lab, Yale Child Study Center, New Haven, CT
P1
N170
Time (ms)
0
-100
100
300
Amplitude (uV)
Participant Demographics
FSIQ (SD)
101.92 (17.69)
96.07 (11.99)
109.67 (22.28)
*groups matched on sex and FSIQ
Experimental Paradigm:
•  Participants were presented with 80 distinct photorealistic, animated faces
matched for low-level visual features.
•  Contingent upon participants’ fixating on the face, stimuli responded by
shifting eye gaze (either from direct to averted or averted to direct).
Fig. 1. Trial Structure. After participants
fixated on a crosshair for ~300ms (panel 1), a
face with either direct or averted gaze was
presented (panel 2). After the participant
looked to the face for at least 500ms, a
second face with shifted gaze (panel 3) was
presented for 600ms. The inter-trial interval
ranged from 200-1200ms.
TD averted -2
ASD direct ASD averted -2.5
SCZ direct 3
6
20
ADOS Total
PANSS
Negative
0
PANSS
Positive
60
10
40
SPQ Total
0
BAP-Q Total
TD
50"
45"
40"
35"
30"
25"
20"
15"
10"
5"
0"
1.5
1
0.5
0
-1
-2
-3
-4
-5
-6
-7
-8
40
44
20
42
35
25
30
30
20
ASD
25
1"
40
0
AQ Total
SCZ
SCZ
5
10
15
20
25
PANSS Positive Scale Score
15
0
ASD
5
10
46
20
15
10
5
20
2.5
2
48
60
15
5
0
50
80
20
80
10
2
1
100
30
25
100
15
4
2
0
25
30
120
30
SRS Total
5
0
Benton Score
RMET Score
3
2
1
0
0
-1
4
8
12
16
20
Correlations
•  Across clinical groups, positive symptoms of
SCZ were associated with greater P1
(r=0.577, p=0.019) and attenuated N170
responses to direct gaze (r=0.642, p=0.007)
•  Higher levels of ASD symptoms were
associated with attenuated P1 response to
direct gaze (r=-0.344, p=0.079)
2"
ADOS Social Communication Total
SCZ averted -3.5
-4
2.50
2.00
1.50
1.00
Direct
Clinical Measures:
To measure social and perceptual difficulties, participants completed:
•  ASD diagnostic assessment: Autism Diagnostic Observation Schedule
•  SCZ diagnostic assessment: Positive and Negative Syndrome Scale
•  ASD self-report measures: Social Responsiveness Scale; Broad Autism
Phenotype Questionnaire; Autism-Spectrum Quotient
•  SCZ self-report measure: Schizotypal Personality Questionnaire
•  Behavioral assessments: Benton Facial Recognition Test; Reading the
Mind in the Eyes Test
4
140
35
8
0
P1
•  Main effect Condition, F(1,39)=5.97,
p=0.02
•  Main effect Group, F(2,39)=5.49, p=0.008
•  In response to direct gaze, P1
amplitude did not differ between ASD
and TD (p=0.64). However, individuals
with SCZ exhibited enhanced P1
response relative to both ASD and TD
groups (ps<0.01).
•  No group differences in P1 latency
In line with a dimensional approach to understanding neurodevelopmental
disorders, preliminary results of this study suggest that neural response to gazecontingent shifts in eye gaze is a reliable marker of social and perceptual
dysfunction across individuals with ASD and SCZ.
•  Greater P1 response is related to higher levels of positive symptoms of SCZ and
lower levels of ASD symptoms. Whereas early sensory responses are intact in
ASD, adults with SCZ show amplified P1 response relative to both TD and ASD.
•  More robust N170 response to direct gaze is associated with fewer positive
symptoms of SCZ. Whereas neural response associated with face processing in
SCZ is similar to that in TD, individuals with ASD show enhanced N170
amplitude relative to both TD and SCZ.
N170
•  Main effect Condition, F(1,39)=5.9,
p=0.009
•  Enhanced amplitude to averted vs.
direct gaze across all groups
•  Across conditions, individuals with ASD
showed greater N170 amplitude relative
to both SCZ (p=0.014) and TD (p=0.06),
whereas individuals with SCZ and TD did
not differ from each other (p=0.49).
•  No group differences in N170 latency
In contrast to ERP markers, clinical measures of ASD and SCZ symptomatology are
variably effective in differentiating the two clinical populations. Specifically, though
self-report measures are reliable in differentiating clinical populations from TD, they
are ineffective in differentiating between diagnostic categories.
0.00
Fixation
5
500
TD direct -1.5
Averted
0.00
Gaze shift to direct when
participant looks to eyes
40
10
6
0
0.50
Onset face with
averted gaze
45
12
7
0
-3
P1 Amplitude (uV)
Age (SD)
22.96 (4.32)
30.45 (8.57)
26.92 (7.33)
N170 Amplitude (uV)
ASD
SCZ
TD
Sex
12M
13M
12M
14
8
-0.5
-1
N
13
14
15
9
P1 Amplitude to Direct Gaze (uV)
Objective: This study aimed to: (i) evaluate P1 and N170 responses to direct
and averted gaze in adults with ASD, SCZ, and TD to determine between-group
differences in neural processes associated with face decoding and (ii) examine
transdiagnostic associations between neural response and social difficulties.
1
0.5
•  ADOS scores differentiated ASD from SCZ, though 3 of 14 participants with SCZ
met criteria for ASD on the ADOS-2.
•  Individuals with SCZ and ASD did not differ on any of the self-report measures of
social functioning, autistic symptomatology, or schizophrenia traits.
•  Both individuals with ASD and SCZ had difficulty with behavioral assessments of
emotion recognition, but only those with ASD had difficulties with face recognition.
P1 Amplitude to Direct Gaze (uV)
The N170 is a negative-going event-related potential (ERP) that is recorded
over occipitotemporal scalp and indexes the earliest stages of face processing.
It is sensitive to point of gaze on the face and is atypical in both ASD and SCZ.
The P1 is an earlier, positive-going ERP that indexes preferential attention to
low-level visual features of stimuli. Previous studies of ERP response to gazerelated cues are limited by their use of static faces, which have questionable
ecological validity. This study utilizes novel methods, integrating eye-tracking
(ET) and electrophysiology (EEG) to study social behavior and brain function
during simulated face-to-face interactions in individuals with ASD, SCZ, and
typical development (TD).
EEG and ET Data Acquisition and Collection:
•  EEG recorded at 1000 Hz with a 128-channel Hydrocel Geodesic Sensor net
•  ET data collected using an Eyelink-1000 remote camera system
ERP Preprocessing and Analysis:
•  Data were filtered from 0.1-100 Hz. ICA was performed to
remove ocular artifact, then data were segmented from -100ms
to 600ms, artifact detected, referenced to average reference,
and baseline corrected.
•  P1 and N170 were extracted from electrodes over right
occipitotemporal scalp from 70-120ms and 120-200ms,
respectively. Peak amplitude and latencies were then included
as dependent variables in repeated measures ANOVAs (with Fig. 2. Recording sites. P1
and N170 were extracted from
group as the independent variable), with follow-up one-way the average of two electrodes
over the right hemisphere.
ANOVAs and t-tests to clarify effects.
N170 Amplitude to Direct
Gaze (uV)
Deficits in maintaining and interpreting social gaze are hallmark features of
autism spectrum disorder (ASD). Individuals with ASD show reduced attention
to direct gaze, attenuated sensitivity to gaze changes, and reduced use of gaze
cues to facilitate facial communication. Atypical gaze processing is not unique to
ASD and is evident in other disorders, including schizophrenia (SCZ). It is
unknown whether specific abnormalities in gaze processing differ by diagnostic
category, or whether they are general indicators of social dysfunction across
neurodevelopmental disorders.
-1.00
-2.00
-3.00
-4.00
-5.00
-6.00
-7.00
TD
ASD
SCZ
50"
45"
40"
35"
30"
25"
20"
15"
10"
5"
0"
1"
2"
These preliminary findings suggest that, across multiple neurodevelopmental
disorders, neural indices of social processing can reveal differences in gaze
processing related to clinically-relevant social and perceptual differences that
behavioral measures of overt symptomatology do not capture.
Funding Sources: NIMH R01 MH100173 (McPartland); NIMH R01 MH100173-02S1 (McPartland); Autism Speaks
Translational Postdoctoral Fellowship (Naples); NARSAD Young Investigator Award (Foss-Feig); Autism Science
Foundation Research Mini Enhancement Grant (Foss-Feig); NIH DP50D012109-02 (Anticevic); NARSAD Young
Investigator Award (Anticevic); Yale Center for Clinical Investigation (Anticevic); NIH R01 MH103831 (Srihari)