Drumming Motor Sequence Training Induces Apparent Myelin Remodelling in Huntington’s Disease: A Longitudinal Diffusion MRI and Quantitative Magnetization Transfer Study

Abstract

Background: Impaired myelination may contribute to Huntington’s disease (HD) pathogenesis. Objective: This study assessed differences in white matter (WM) microstructure between HD patients and controls, and tested whether drumming training stimulates WM remodelling in HD. Furthermore, it examined whether training-induced microstructural changes are related to improvements in motor and cognitive function. Methods: Participants undertook two months of drumming exercises. Working memory and executive function were assessed before and post-training. Changes in WM microstructure were investigated with diffusion tensor magnetic resonance imaging (DT-MRI)-based metrics, the restricted diffusion signal fraction (Fr) from the composite hindered and restricted model of diffusion (CHARMED) and the macromolecular proton fraction (MPF) from quantitative magnetization transfer (qMT) imaging. WM pathways linking putamen and supplementary motor areas (SMA-Putamen), and three segments of the corpus callosum (CCI, CCII, CCIII) were studied using deterministic tractography. Baseline MPF differences between patients and controls were assessed with tract-based spatial statistics. Results: MPF was reduced in the mid-section of the CC in HD subjects at baseline, while a significantly greater change in MPF was detected in HD patients relative to controls in the CCII, CCIII, and the right SMA-putamen post-training. Further, although patients improved their drumming and executive function performance, such improvements did not correlate with microstructural changes. Increased MPF suggests training-induced myelin changes in HD. Conclusion: Though only preliminary and based on a small sample size, these results suggest that tailored behavioural stimulation may lead to neural benefits in early HD, that could be exploited for delaying disease progression.