Baseline Large-Scale Network Dynamics Associated with Disease Progression in Huntington's Disease

Background: Huntington's disease (HD) is a genetically determined disease with motor, cognitive, and neuropsychiatric disorders. However, the links between clinical progression and disruptions to dynamics in motor and cognitive large-scale networks are not well established.

Objective: To investigate changes in dynamic and static large-scale networks using an established tool of disease progression in Huntington's disease, the composite Unified Huntington's Disease Rating Scale (cUHDRS).

Methods: Sixty-four mutation carriers were included. Static and dynamic baseline functional connectivity as well as topological features were correlated to 2-year follow-up clinical assessments using the cUHDRS.

Results: Decline in cUHDRS scores was associated with higher connectivity between frontal default-mode and motor networks, whereas higher connectivity in posterior, mainly visuospatial regions was associated with a smaller decline in cUHDRS scores.

Conclusions: Structural disruptions in HD were evident both in posterior parietal/occipital and frontal motor regions, with reciprocal increases in functional connectivity. However, although higher visuospatial network connectivity was tied to a smaller cUHDRS decline, increased motor and frontal default-mode connections were linked to a larger cUHDRS decreases. Therefore, divergent functional compensation mechanisms might be at play in the clinical evolution of HD.