Functional connectivity differences in early infancy precede autism symptoms: a multivariate pattern analysis

Functional brain connectivity is altered in children and adults with autism spectrum disorder (ASD). Mapping pre-symptomatic functional disruptions in ASD could identify infants based on neural risk, providing a crucial opportunity to mediate outcomes before behavioral symptoms emerge. Here we quantify functional connectivity using scalable EEG measures of oscillatory phase coherence (6-12Hz). Infants at high and low familial risk for ASD (N=65) underwent an EEG recording at 3 months of age and were assessed for ASD symptoms at 18 months using the Autism Diagnostic Observation Schedule-Toddler Module. Multivariate pattern analysis was used to examine early functional patterns that are associated with later ASD symptoms. Support vector regression (SVR) algorithms accurately predicted observed ASD symptoms at 18 months from EEG data at 3 months (r=0.76, p=0.02). Specifically, lower frontal connectivity and higher right temporo-parietal connectivity predicted higher ASD symptoms. The SVR model did not predict non-verbal cognitive abilities at 18 months (r=0.15, p=0.36), suggesting specificity of these brain alterations to ASD. These data suggest that frontal and temporo-parietal dysconnectivity play important roles in the early pathophysiology of ASD. Early functional differences in ASD can be captured using EEG during infancy and may inform much-needed advancements in the early detection of ASD.