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

Mov Disord. 2024 Jan;39(1):197-203. doi: 10.1002/mds.29655. Epub 2023 Dec 26.

Abstract

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.

Keywords: Huntington's disease; functional MRI.

MeSH terms

  • Brain / diagnostic imaging
  • Disease Progression
  • Frontal Lobe
  • Humans
  • Huntington Disease* / diagnostic imaging
  • Huntington Disease* / genetics
  • Magnetic Resonance Imaging