Neonatal connectome as a predictor of social and attentional impairment in ASD

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Limited attention to faces of conspecifics constitutes one of the markers of ASD.1-4 Limited attention to faces is associated with increased severity of autism symptoms and poor adaptive functioning,5-8 and early individual differences in attention to faces contribute to the variability in later social and cognitive outcomes.5 Attention to faces is enhanced in 6-month-old unaffected females at familial risk for ASD and predicts better social functioning 1.5 years later.9 Despite the well-documented role that monitoring faces of conspecifics plays in socio-cognitive development, the brain mechanisms underlying such deficits in ASD are unknown and treatments typically focus on ameliorating symptoms rather than addressing underlying causes. Considering that signs of atypical attention to faces are evident by 6 to 9 months in infants later diagnosed with ASD both in laboratory1-3, 10 and real-world environments, 11-13, [Preliminary Study (PS#1)], we hypothesize that the neural foundations for these impairments are already reflected in functional brain organization (the connectome) at birth. Attentional functions in the brain are subserved by the Salience Network (SN), the Executive Control Network (ECN), and the Default Mode Network (DMN), all of which have been implicated in ASD,14-16 and have been found to be atypical in newborns at risk for ASD due to non-familial factors (PS#2). Here we propose to examine whether, when compared to unaffected high-risk (HR) and low-risk (LR) newborns, HR newborns who, at 24 months, meet criteria for ASD exhibit abnormal strength of functional connectivity within the three networks. We will also examine whether the strength of functional connectivity in the three networks at birth is predictive of later performance on a selective social attention (SSA) eye-tracking task at 6 and 24 months and severity of autism symptoms at 24 months. By targeting neonates, we plan to investigate properties of attentional networks known to be affected in ASD14-16 before they are shaped extensively by extra-uterine experience. To achieve these aims, we propose to study 120 neonates who have an older sibling with ASD (HR) and 30 neonates without familial history of ASD (LR). The neonates will undergo a resting-state functional connectivity MRI (rs fcMRI) at 42-44 post-menstrual weeks and at 6 and 24 months will be administered the SSA task. Performance on this task discriminates between ASD and non-ASD groups during prodromal stages of the disorder in high-risk siblings of children with ASD,1 in clinic-referred toddlers newly diagnosed with ASD,17 and in school-age children (PS#3) and shows strong associations with autism symptom severity5 (PS#3). Diagnostic assessment will be completed at 24 months through which severity of autism symptoms and diagnostic grouping will be determined. The project advances integration of psychological and brain science in autism by investigating whether functional brain organization in ASD is altered at birth and, if so, how this disruption affects social development in infants at risk for ASD.