Impact of Huntington's Disease on Mental Rotation Performance in Motor Pre-Symptomatic Individuals

Background: Huntington's disease (HD) is a genetic disorder known for affecting motor control. Despite evidence for the impact of HD on visual cortico-striatal loops, evidence for impaired visual perception in early symptomatic HD patients is limited; much less is known about what happens during the HD prodrome. Objective: The goals of this study were to evaluate perceptual processing in motor pre-manifest HD gene-carriers (Pre-HDs) during a visual mental rotation task. Methods: To achieve this goal, 79 participants including 24 Pre-HD participants and 55 healthy matched controls were scanned using functional MRI as they performed a mental rotation task. Another group of 36 subjects including 15 Pre-HDs and 21 healthy age/gender matched controls participated in a control behavioral test of judgment of line orientation outside the scanner. Results: We found that, although Pre-HDs (in this stage of disease) did not demonstrate slower response times, their response accuracy was lower than controls. On the fMRI task, controls showed a significant decrease in activity in the occipito-temporal (OT) visual network and increase in activity in the caudo-fronto-parietal (CFP) network with mental rotation load. Interestingly, the amount of mental rotation-related activity decrease in the OT network was reduced in Pre-HDs compared to controls while, the level of CFP response remained unchanged between the two groups. Comparing the link between the evoked BOLD activity within these networks and response accuracy (i.e., behavior), we found that the models fit to data from controls were less accurate in predicting response accuracy of Pre-HDs. Conclusion: These findings provide some of the earliest functional evidence of impaired visual processing and altered neural processing underlying visual perceptual decision making during the HD prodrome.