This grant provides support for an NIH Autism Center of Excellence (ACE). Autism is characterized by tremendous phenotypic heterogeneity likely due to its complex genetic and neural underpinnings. There is mounting evidence of decreased responsivity to social stimuli and altered patterns of brain connectivity in individuals with autism specrum disorders (ASD), and aberrant functional and structural connectivity is related to genetic vulnerability to the disorder. This project will systematically chart longitudinal changes in brain activity and connectivity in children with and without ASD, relating the observed developmental trajectories to both behavioral phenotypes and autism risk genes. More specifically, using a longitudinal design, functional magnetic resonance imaging (fMRI), resting-state fMRI (rs-fMRI) and diffusion tensor imaging (DTI) will be performed at two timepoints (3 years apart) in two previously characterized age cohorts, and relate these data to behavioral phenotypes and ASD risk polymorphisms. This integrated research approach will identify the earliest departures from typical development and delineate the complex interactions among genes, brain, and behavior that drive development of ASD.