Abstract

Huntington's disease (HD), a progressive neurological disorder involving degeneration in basal ganglia structures, leads to abnormal control of saccadic eye movements. We investigated whether saccadic impairments in HD (N = 9) correlated with clinical disease severity to determine the relationship between saccadic control and basal ganglia pathology. HD patients and age/sex-matched controls performed various eye movement tasks that required the execution or suppression of automatic or voluntary saccades. In the "immediate" saccade tasks, subjects were instructed to look either toward (pro-saccade) or away from (anti-saccade) a peripheral stimulus. In the "delayed" saccade tasks (pro-/anti-saccades; delayed memory-guided sequential saccades), subjects were instructed to wait for a central fixation point to disappear before initiating saccades towards or away from a peripheral stimulus that had appeared previously. In all tasks, mean saccadic reaction time was longer and more variable amongst the HD patients. On immediate anti-saccade trials, the occurrence of direction errors (pro-saccades initiated toward stimulus) was higher in the HD patients. In the delayed tasks, timing errors (eye movements made prior to the go signal) were also greater in the HD patients. The increased variability in saccadic reaction times and occurrence of errors (both timing and direction errors) were highly correlated with disease severity, as assessed with the Unified Huntington's Disease Rating Scale, suggesting that saccadic impairments worsen as the disease progresses. Thus, performance on voluntary saccade paradigms provides a sensitive indicator of disease progression in HD.

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