Development and neural mechanisms of repetitive behavior and sensory responsivity in autism

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Project Summary Restricted and repetitive behaviors (RRB), which under the DSM 5 now include unusual responses to sensory stimuli, are defining features of autism spectrum disorder (ASD) that impede upon adaptive opportunities and play a significant role in lowering quality of life for affected individuals and their families. Despite long standing acknowledgement of these impacts, the neurodevelopmental mechanisms underlying subtypes of RRB are poorly understood, and effective intervention and prevention strategies are severely limited. The long term goal for this project is to utilize developmental behavioral and neuroimaging data to develop risk markers and novel early individualized intervention and strategic prevention strategies targeted to the domain of restricted and repetitive behaviors. The primary objective of the present application is to characterize the neurodevelopmental and behavioral mechanisms underlying specific subtypes and profiles of RRB in a prospectively ascertained sample of children with and without ASD. We will accomplish this objective through partnership with the NIH Autism Center of Excellence Network Infant Brain Imaging Study (IBIS), an ongoing prospective, longitudinal brain imaging study of children with and without autism from infancy through school age. Our central hypothesis is that distinct, biologically informative RRB subtypes will be identified at school-age, and that these subtypes will have emerged through, and be presaged by, a dynamic developmental process beginning in infancy. Identifying behavioral and neurodevelopmental precursors of restricted and repetitive behaviors will provide new and necessary footholds for the creation of early detection and mechanism-based prevention/intervention strategies. The objectives of this application will be addressed through three specific aims: 1) characterize fine-grained dimensions and profiles of RRB in relation to brain development from infancy through school-age; 2) empirically derive infant/toddler age risk markers for later RRB; and 3) explore the relations between RRB and the home and school environments. Existing longitudinal brain imaging and behavioral data collected through IBIS will be integrated with new measures specifically designed by our team to capture dimensions of restricted and repetitive behavior (including direct quantitative measures of sensory responsivity), as well as rich information pertaining to the environments in which these behaviors occur. This work is innovative in that it offers an unprecedented opportunity to comprehensively chart the behavioral and neurodevelopmental mechanisms underlying specific RRB subtypes and identify early-emerging markers of later outcomes. Results from this project will inform: 1) the pathogenesis of subtypes of RRB, 2) their relations to each other and to the external environment, and 3) set the stage for the development of early screening and targeted prevention/intervention procedures.