The field of autism spectrum disorder (ASD) research lacks objective, sensitive quantifications of symptomatology with sufficient evidence to justify use as biomarkers in clinical trials. In the current proposal we investigate two promising markers, neural response to faces, measured by electroencephalogram (EEG), and visual attention to faces, measured by eye-tracking (ET). Published work and our preliminary data indicate that these measures: reflect clinically meaningful differences in the core symptoms of ASD, both by discriminating groups with ASD from those with typical development (TD) and by correlating with symptomatology in individuals with ASD; have strong test-retest reliability; demonstrate sensitivity to change in clinical status, both in the context of pharmacological and behavioral intervention; are collected by objective, automated tools not vulnerable to issues associated with inter-rater or inter-operator reliability; are minimally invasive and highly tolerable and therefore applicable across a wide range of ages and functional levels, with acceptable burden for participants and families; are collected using economical and accessible technologies that are scalable for large multisite studies with potential utility in the near term. Despite the promise of these biomarkers, their appropriateness in individuals with ASD and intellectual disability (ASD+ID) is poorly understood. In this application, we propose a novel integration of technologies and an innovative experimental approach to investigate these promising biomarkers in this critically understudied population. We leverage two complementary lines of research developed by the PIs: Dr. McPartland's Autism Biomarkers Consortium for Clinical Trials (ABC-CT), a multisite study collecting large samples of highly reliable EEG and ET data in children with ASD, and Dr. Naples' suite of gaze- and behaviorally-contingent technologies permitting concurrent collection of ET and EEG data in individuals with severe ID. The proposed work will incorporate robust ABC-CT experiments into an innovative experimental approach to study 30 6-11 year old children with ASD+ID and a matched sample of 30 individuals with ID without ASD. We test the hypotheses that individuals with ASD+ID will display longer latency of the N170 event-related potential (ERP) to human faces and reduced proportion of looking time to human faces in static social scenes relative to individuals with ID without ASD and that face N170 and visual attention to faces will correlate with clinician and caregiver ratings of social- communicative function. This innovative project uses a suite of contingent technologies to acclimate participants to the testing environment and apparatus, to attenuate motion, to permit real time feedback on data quality to prioritize stimulus delivery, and to support post-processing of motion artifact using computer vision derived motion estimates. By adapting robust markers for administration to individuals with ASD and ID, this application holds promise for development of biomarkers viable in an understudied but critically important segment of the autism spectrum.

Public Health Relevance

This individuals project investigates objective measures of social and communicative with autism spectrum disorder and intellectual disability. behavior and brain activity in This research holds promise for developing novel approaches to studying individuals with significant intellectual disability and for creating new tools to inform treatment selection and measure treatment response in autism spectrum disorder.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1)
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Gilotty, Lisa
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Yale University
Schools of Medicine
New Haven
United States
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