Abstract
Objectives: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder that affects first basal ganglia and fronto- striatal circuitry. Cognitive decline and inhibitory control deficits are more subtle in the early stages of manifest disease, yet relevant to track disease progression. The current study aims to underpin and characterize the dysfunction of oculomotor inhibitory control mechanisms and executive function through working memory demands on fronto-executive load in a cohort of early manifest HD (Early-HD).
Methods: A comprehensive battery of neuropsychological tests was applied to assess cognitive functioning in 14 Early-HD and 22 Control participants. Oculomotor function was studied using an experimental paradigm comprising four oculomotor tasks: prosaccade, antisaccade, 1- or 2-back memory prosaccade, and 1- or 2-back memory antisaccade. The estimated metrics were success rate, direction errors, timing errors, and the primary saccade latency.
Results: The Early-HD group demonstrated cognitive deficits in visual and verbal memory, executive function, attention, visual perception, and verbal and non-verbal IQ domains. Regarding oculomotor performance, the clinical group had a decreased success rate and increased percentage of direction errors and early premature saccades while exhibiting faster response times than the Control group in the 1- or 2-back memory antisaccade task.
Conclusions: Our results demonstrate overt oculomotor dysfunction in Early-HD since inhibitory control mechanisms are necessary to perform the task. Furthermore, increasing working memory demands and fronto-executive load enhances impulsive response patterns. The dysfunction in goal-oriented oculomotor behavior, including more automatized responses and deficits in inhibition, is present in Early- HD patients with cognitive deficits but who remain functional and autonomous. These findings reinforce the notion that fronto-striatal impairment is a crucial event in HD and that more automatized oculomotor evaluation procedures help identify and stratify deficits in early manifest disease.