DESCRIPTION (provided by applicant): This center focuses on elucidating fundamental information processing and neurobiological mechanisms causing autism. It incorporates 5 themes: 1) autism as a disorder of complex information processing abilities WITH intact or enhanced basic abilities; 2) autism as a disturbance in cerebral connectivity with under connectivity of long-distance connections and over-connectivity of compensatory local connections; 3) autism as a developmental disorder whose brain-behavioral manifestations change with each stage of brain maturation from childhood to adulthood; 4) that the pathognomonic social impairments are best understood in terms of underlying information processing mechanisms; and 5) that emotional and affective impairments are a major component of the syndrome and significant contributor to impaired function and serious behavior issues. These goals will be addressed using behavioral, cognitive, fMRI, DTI, DTT, and neuropathologic studies of: infant siblings, first-diagnosed toddlers with autism, and groups of children, adolescents, and adults with and without autism. Project I: Development of Categorization & Facial Knowledge in Low & High Functioning Autism; Project II: Disturbances of Affective Contact: Development of Brain Mechanisms for Emotion Processing; Project III: Systems Connectivity & Brain Activation: Imaging Studies of Language & Perception; Project IV: Diffusion Tensor MRI & Histopathology of Brain Microstructure & Fiber Pathways. Project I focuses on understanding the earliest manifestations of autism and the development of earlier diagnostic tools; it also focuses on information processing mechanisms underlying social and cognitive symptoms. Project II focuses on elucidating emotion processing mechanisms and the maturational disturbances from childhood through adulthood; these studies will clarify how individuals with autism experience, understand and regulate emotion, and will also examine their self-awareness of emotion. Genetic modifiers of emotionality will also be determined. Project III focuses on understanding disturbances in functional brain connectivity that underlie the impaired processing of information and in turn the cognitive and behavioral impairments in autism. The project also includes innovative machine-learning studies of how the brain identifies and categorizes words and computational modeling of cortical function. Project IV looks at structural connectivity of specific white matter pathways and the histopathology of intra-cortical white matter projections. This project will help reconcile the functional under-connectivity and early structural overgrowth in autism. The identification of fundamental information processing mechanisms underlying the behavior of autism will lead to the development of more specific and effective interventions; similarly identification of connectivity alterations can lead to targeted cognitive interventions that increase neural connectivity. This research addresses Autism Research Matrix goals # 1,2,3,6,16,17,19,22,23,26,31,and 34.