Oculomotor studies of cerebellar function in autism

Abstract

Histopathological, neuroimaging and genetic findings indicate cerebellar abnormalities in autism, but the extent of neurophysiological dysfunction associated with those findings has not been systematically examined. Suppression of intrusive saccades (square wave jerks) and the ability to sustain eccentric gaze, two phenomena requiring intact cerebellar function, were examined in 52 high-functioning individuals with autism and 52 age- and IQ-matched healthy subjects during visual fixation of static central and peripheral targets. Rates of intrusive saccades were not increased in autism during visual fixation, and foveopetal ocular drift was also not increased when subjects held an eccentric gaze. The absence of gross disturbances of visual fixation associated with cerebellar disease in individuals with autism, such as increased square wave jerk rates and foveopetal drift when holding eccentric gaze, indicates that the functional integrity of cerebellar–brainstem networks devoted to oculomotor control is preserved in autism despite reported anatomic variations. However, increased amplitude of intrusive saccades and reduced latency of target refixation after intrusive saccades were observed in individuals with autism, especially when subjects maintained fixation of remembered target locations without sensory guidance. The atypical metrics of intrusive saccades that were observed may be attributable to faulty functional connectivity in cortico-cerebellar networks.

Introduction

Autism is a complex, polygenetic neurodevelopmental disorder characterized by deficits in social relatedness and verbal and nonverbal communication, as well as restricted and repetitive behaviors. The developmental neurobiology of this disorder, particularly with regard to the brain regions most commonly and severely affected, is not yet well understood. Widespread abnormalities observed in neocortex suggest atypical patterns of cortical connectivity leading to reduced integration within functional brain systems and, consequently, deficits in complex information processing (Minshew et al., 1997, Schultz et al., 2000, Just et al., 2004). While studies have acknowledged the contribution of underconnectivity in corticocortical tracks to the pathophysiology of autism, potentially important connections involving the cerebellum have not been thoroughly explored. This is potentially important given histopathological findings in the cerebellum (Ritvo et al., 1986, Bauman, 1991, Kemper and Bauman, 1993).

Eye movement testing is a widely used clinical approach for evaluating cerebellar function. Most previous quantitative studies of eye movements in autistic individuals have not reported significant disturbances in the latency, accuracy or peak velocity of visually guided saccades; however, we recently reported mild saccadic dysmetria in a large patient sample (Rosenhall et al., 1988, Minshew et al., 1999, Goldberg et al., 2002, Minshew et al., 2002, Takarae et al., 2004b). Examining the stability of visual fixation is another way of investigating the functional integrity of cerebellar and brainstem systems. Although gaze behavior in autism has been studied to characterize how individuals with autism explore visual scenes, the basic neurophysiological functioning of the visual fixation system has not been systematically examined (Klin et al., 2002).

In this study, we examined intrusive square wave jerks (SWJs) during visual fixation of static central and eccentric targets. An increased rate of SWJs, resulting from reduced inhibitory control of pretectal oculomotor structures, is a known consequence of cerebellar pathology (Zee et al., 1976, Dell'Osso et al., 1977). The metrics of SWJs were analyzed to explore potential alterations in saccade inhibition. We also evaluated foveopetal ocular drift during fixation of eccentric targets, which can be increased with impaired flocculus and paraflocculus function (Zee et al., 1980).