ABSTRACT Functional brain network characteristics reflect both genetic and environmental influences on brain development during fetal and postnatal periods. Alterations in network characteristics signal the presence of pathogenic factors and their potential mechanisms of action, which is crucial for the identification of processes that enhance risk for future onset of behavioral symptoms. Considering that autism features are distributed in the general population and are enriched in children with family members diagnosed with autism, the present study examines links between neonatal connectome and later social outcomes in a large sample of infants with and without familial history of autism (FHA). The outcomes of interest are (a) social attention which represents one of the most robust biomarkers reported in infants, toddlers, and school-aged children with autism, and (b) social engagement skills which represent a core feature associated with autism in toddlers. Towards these aims, we propose to examine prospective associations between iFC and later social phenotypic outcomes in a prospective sample of infants with (N=140) and without (N=60) FHA. By combining the two groups and adopting a dimensional approach to outcome measures, we aim to capture both the clinical and the subclinical variation in symptoms, which is critical for understanding the link between altered brain development and psychopathology. Brain imaging data will be collected at 42-44 weeks postmenstrual age (PMA); selective social attention measures will be collected at 6 and 18 months, and social engagement measure will be collected at 18 months. Social attention will be quantified using the Selective Social Attention (SSA) 2.0 eye- tracking task developed and validated in our lab. A composite social engagement score will be computed based on direct observation and parent report using standardized assessment tools: ADOS-2 and ADI-R. Aims 1 and 2 will focus on examining prospective links between inter- and intra-network iFC of the SN, DMN, FPN, and amygdala networks and later social attentional and social engagement outcomes. To complement the hypotheses-driven Aims, in Aim 3 we will conduct a data-driven whole brain analysis. This study will identify the characteristics of the neonatal connectome linked prospectively with behavioral dimensions known to be affected in autism, creating potential for improving identification of early brain-based risk factors and implementation of early interventions to support social attention and engagement in infancy and early childhood.

NARRATIVE The proposed study examines resting state functional brain connectivity in infants with and without a family history of autism followed from birth to 18 months. The study will characterize the brain connectome during a period of extremely rapid development and plasticity, and test predictive models to demonstrate that the early changes in the connectome are meaningful and related to the core social features of autism. The study has great potential for improving identification of early brain-based risk factors for development of social difficulties and implementation of early interventions to support social attention and engagement in infancy and early childhood.