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

Abstract

AbstractBackgroundHuntington'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.ObjectiveTo 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).MethodsSixty‐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.ResultsDecline 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.ConclusionsStructural 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.