This is an Autism Center of Excellence (ACE) Network grant. Multiple lines of converging evidence (from magnetic resonance imaging (MRI), post-mortem, and head circumference studies) document brain enlargement in autism, with some evidence of this within the first year of life. New imaging methods provide highly detailed MRI data and are well suited for rapid scanning of very young children. In addition, new behavioral assessment tools enable the efficient screening and detection, at 12 months, of infants who are likely to meet criteria for autism at age two. The initial grant supported a prospective, longitudinal examination of brain and behavior at 6, 12 and 24 months in infants at high familial risk (HR) for autism. Results revealed that HR infants who go on to have autism at 24 months have impairments in visual orienting and motor behavior at 6 months of age, and that aberrant white matter tract development is detectable by 6 months of age in these infants. This demonstrates that brain changes occur concurrently with the emergence of behavioral abnormalities in ASD and that brain and behavior changes during the 1st year (and as early as 6 months of age) are critically important in the onset and development of autistic behavior. In this study, these findings will be followed up by conducting earlier (3 months), more frequent (3, 6, 9, 12, 15, 24 months), and more in depth examination of the trajectories of brain and behavior development in 200 HR and 60 LR (low familial risk) infants, to more fully understand brain-behavior relationships during this critically important period preceding and coinciding with the emergence of the defining features of autism. In addition, follow up behavioral/diagnostic evaluations of the original sample of 400 HR subjects will be conducted at 36 to 60 months of age, a time when the diagnosis of autism is considered to be more stable. Child and family level characteristics relevant to elucidating an early prediction model of later autism will also be assessed in the joint cohort of 600 HR subjects. The delineation of brain and behavior trajectories in early development and the ability to predict autism diagnosis from preclinical risk markers during infancy, prior to clinical diagnosis and during a period of substantial post-natal brain plasticity, when children may benefit maximally from early detection and intervention, has the potential to significantly improve the lives of affected individuals.