Altered Thalamocortical Connectivity in Six-Week Old Infants at High Familial Risk for Autism Spectrum Disorder

Abstract

Converging evidence from neuroimaging studies has revealed altered connectivity in cortical-subcortical networks in youth and adults with autism spectrum disorder (ASD). Comparatively little is known about the development of cortical-subcortical connectivity in infancy, before the emergence of overt ASD symptomatology. Here we examined early functional and structural connectivity of thalamocortical networks in infants at high familial risk for ASD (HR) and lowrisk controls (LR). Resting-state functional connectivity (rs-fcMRI) and diffusion tensor imaging (DTI) data were acquired 52 six-week-old infants. Functional connectivity was examined between six cortical seeds -prefrontal, motor, somatosensory, temporal, parietal, and occipital regions- and bilateral thalamus. We found significant thalamic-prefrontal underconnectivity, as well as thalamic-occipital and thalamic-motor overconnectivity in HR infants, relative to LR infants. Subsequent structural connectivity analyses also revealed atypical white matter integrity in thalamic-occipital tracts in HR infants, compared to LR infants. Notably, aberrant rs-fcMRI and DTI connectivity indices at 6 weeks predicted atypical social development between 6 and 36 months of age, as assessed with eye-tracking and diagnostic measures. These findings indicate that thalamocortical connectivity is disrupted at both the functional and structural level in HR infants as early as six weeks of age, providing a possible early marker of risk for ASD.