Disentangling the neurobiological bases of temporal impulsivity in Huntington's disease

Despite its impact on daily life, impulsivity in Huntington's disease (HD) is understudied as a neuropsychiatric symptom. Our aim is to characterize temporal impulsivity in HD and to disentangle the white matter correlate associated with impulsivity.

Forty-seven HD individuals and 36 healthy controls were scanned and evaluated for temporal impulsivity using a delay-discounting (DD) task and complementary Sensitivity to Punishment and Sensitivity to Reward Questionnaire. Diffusion tensor imaging was employed to characterize the structural connectivity of three limbic tracts: the uncinate fasciculus (UF), the accumbofrontal tract (NAcc-OFC), and the dorsolateral prefrontal cortex connectig the caudate nucleus (DLPFC-cn). Multiple linear regression analyses were applied to analyze the relationship between impulsive behavior and white matter microstructural integrity.

Our results revealed altered structural connectivity in the DLPC-cn, the NAcc-OFC and the UF in HD individuals. At the same time, the variability in structural connectivity of these tracts was associated with the individual differences in temporal impulsivity. Specifically, increased structural connectivity in the right NAcc-OFC and reduced connectivity in the left UF were associated with higher temporal impulsivity scores.

The present findings highlight the importance of investigating the spectrum of temporal impulsivity in HD. As, while less prevalent than other psychiatric features, this symptom is still reported to significantly impact the quality of life of patients and caregivers. This study provides evidence that individual differences observed in temporal impulsivity may be explained by variability in limbic frontostriatal tracts, while shedding light on the role of sensitivity to reward in modulating impulsive behavior through the selection of immediate rewards.