Pursuit Eye Movement Abnormalities in First-Degree Relatives of Individuals with Autism

Background: Pursuit eye movement precision is a heritable trait that enables visual tracking of moving targets. Two phases of smooth pursuit have been identified that engage separate, but overlapping, neural systems. The first 100ms of pursuit is referred to as the “open-loop” phase, and is driven by sensory analysis of target motion. Pursuit after the first 100ms of pursuit initiation is considered “closed-loop”, and is more dependent upon predictions of target velocity and ongoing feedback about performance. Individuals with autism have demonstrated reduced open-loop accuracy for rightward-moving targets, as well as bilaterally reduced closed-loop pursuit accuracy. Pursuit performance in unaffected relatives of individuals with autism has not been systematically investigated, but may yield useful endophenotypes for the disorder.

Objectives: To investigate pursuit eye movements in first-degree relatives of individuals with autism. 

Methods: Fifty-nine first-degree relatives (parents and siblings) of individuals with autism and 38 age- and IQ-matched healthy control individuals between 8-55 years of age performed a step-forward pursuit task. Participants initially maintained fixation of a central target, after which the target stepped 3 degrees left or right of center and then continued to move in the same direction at constant velocity. The latency and accuracy of the initial saccade made to acquire the target, as well as the latency and accuracy of the ensuing open- and closed-loop pursuit were measured.

Results: Relatives of affected individuals evidenced reduced open-loop accuracy to rightward targets and reduced closed-loop accuracy bilaterally, consistent with the pattern of results reported previously in individuals with autism. The latency and accuracy of the initial catch-up saccade and the latency of pursuit initiation did not differ between groups.

Conclusions: Family members of individuals with autism show deficits in pursuit eye movements relative to controls that directly parallel findings we have previously described in an independent sample of autism probands. Reduced open-loop accuracy to rightward targets is a highly atypical finding, and suggests distinct disturbances in sensory processing of visual motion mediated by left extrastriate cortex, or in sensorimotor transformations by cortical eye fields and cerebellum. Additionally, bilateral reductions in closed-loop accuracy indicate impairment in the ability to use feedback about the accuracy of tracking to reduce error that is not hemisphere-specific. These findings are consistent with reports of altered functional connectivity in autism that may be more pronounced in the left hemisphere, as well as evidence of cerebellar pathology.  Importantly, our findings suggest that such alterations and their impact may be familial, and thus provide a useful and highly specific neurophysiological endophenotype for autism research.