Eye position feedback in a model of the vestibulo-ocular reflex for spino-cerebellar ataxia 6

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases characterized by progressive instability of posture and gait, incoordination, ocular motor dysfunction, and dysarthria due to degeneration of cerebellar and brainstem neurons. Recent studies have established that there are more than 16 genetically distinct subtypes. Clinical observations suggest that eye movements and postural stability are universally but differentially impaired in the SCAs. The aim of the present work was to study the horizontal vestibulo-ocular reflex (VOR) in SCA6 patients to understand the pathophysiology of the VOR due to cerebellar Purkinje cell degeneration. The VOR was recorded in patients with genetically defined SCA6 during rotation in the dark. Severely affected subjects had an intact VOR, but there were quantitative differences in the gain and dynamics compared to normal controls. During angular velocity ramp rotations, there was a reversal in the direction of the VOR that was more pronounced in SCA6 compared to controls. Modeling studies indicate that abnormal feedback of an eye position signal into the velocity storage network can account for this reversal. These and other results will help to identify features that are diagnostic for SCA subtypes and provide new information about selective vulnerability of neurons controlling vestibular reflexes.