Connectivity in social brain systems in autism

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DESCRIPTION (provided by applicant): Autism spectrum disorders (ASDs) are brain-based developmental disorders, but their specific neural bases are not yet understood. Studies investigating both social brain theories and interconnectivity theories of ASD have obtained mixed results, reflecting the heterogeneity observed in the clinical phenotype. This application proposes to develop novel experimental and analytic approaches to examine connectivity within specific brain systems subserving social information processing in ASD. The innovative experimental method incorporates both dynamic and static stimuli, enabling extraction of both event-related potentials (ERPs) and oscillatory electroencephalographic (EEG) activity reflecting stages of face perception and action perception systems. A cutting-edge analytic approach applies structural equation modeling (SEM) to test a proposed model of connectivity among these facets of the social brain and related social function (assessed through standardized behavioral assessments and ecologically valid parent report measures of real-world behavior). This groundbreaking approach will be the first to apply SEM to electrophysiological data in ASD, providing insight into temporal aspects of connectivity inaccessible to other imaging methods. A specific model of effective connectivity will be tested, and SEM will also be employed to explore alternative models that may explain variance between individuals with ASD and typical participants, as well as variation within ASD. The significance of this project lies in elucidating the inconsistent results obtained by prior work using conventional analytic methods; the proposed innovations will provide new tools to parse heterogeneity in ASD by examining function at individual stages of social perception as well as the level of neural systems. The project entails collaboration between early stage investigators with complementary expertise and synergy with extant research programs at two major autism research centers; pooling of electrophysiological data from two sites using identical procedures and hardware is a logistical advance unto itself with the potential to accelerate the pace of research at both sites. The proposed SEM approach has elucidated gene-brain-behavior relationships in other psychiatric disorders and will lead to future research integrating behavioral and electrophysiological data with ongoing genotyping projects at both sites. PUBLIC HEALTH RELEVANCE: This research studies the brain bases for social difficulties in autism by examining the integrity of brain systems supporting face perception and imitation. By understanding patterns of connectivity in these brain circuits, the study may shed light on causes of the disorder, ways to identify the disorder at younger ages, and avenues for treatment.