Along-Tract Diffusion Alterations in the Dentato-Rubro-Thalamic Tract Correlate with Motor and Cognitive Decline in Huntington's Disease

Motivation: Despite the critical role of the cerebellum and related brain circuits in motor and cognitive function, understanding of the dentato-rubro-thalamic tract (DRTT) changes in Huntington's disease (HD) is limited. Goal(s): By examining DRTT microstructural alterations, we aim to clarify their relationship with HD progression and symptom severity. Approach: Using DRTT tractography, we extracted along-tract mean diffusivity (MD) and fractional anisotropy (FA) values, comparing them across healthy controls, premanifest, and manifest HD individuals, and correlating them with clinical measures of motor and cognitive function. Results: Significant FA and MD differences across DRTT regions significantly correlated with motor and cognitive scores. Impact: This study reveals the DRTT's involvement in HD progression and underscores the importance of examining regional changes along the tract, providing valuable insights into white matter alterations and potential new biomarkers of motor and cognitive impairments in HD.