Abstract

Evidence suggests that autism spectrum disorders (ASD) are etiologically diverse. In the context of this diversity, identifying discrete pathways of familial risk is crucial for gene discovery. Family studies are well-suited for determining biologically homogeneous subgroups, or biological characteristics that are differentially expressed across affected individuals and families. Our data indicate that individuals with ASD show patterns of oculomotor alterations consistent with dysfunction of three specific neural circuits: cerebellar-pontine circuitry that maintains motor precision, left hemisphere frontotemporal circuitry supporting sensorimotor transformations during rightward open-loop visual pursuit, and prefrontal systems involved in cognitive control of sensorimotor responses. Interestingly, we recently identified a similar profile of sensorimotor and cognitive alterations in unaffected first-degree relatives of individuals with ASD, suggesting that these discrete brain systems may serve as useful biological intermediate phenotypes for family genetic and pathophysiologic studies of ASD.