Abstract
Background: Huntington’s disease (HD) is a neurodegenerative disorder leading to debilitating cognitive and motor symptoms. Impaired myelination may contribute to HD pathogenesis. We assessed baseline differences in apparent white matter (WM) myelination between HD patients and controls, and tested whether drumming training stimulates myelin remodelling in HD. We also examined whether microstructural changes were related to changes in motor and cognitive function. Methods: Participants undertook two months of drumming exercises. Different aspects of working memory and executive function were assessed before and after the training. For comparability with previous studies, we assessed training-related changes in diffusion tensor magnetic resonance imaging (DT-MRI)-based metrics of fractional anisotropy (FA) and radial diffusivity (RD). Moving beyond DT-MRI, we also tested changes in the restricted diffusion signal fraction (Fr) from the composite hindered and restricted model of diffusion (CHARMED) and in the macromolecular proton fraction (MPF) from quantitative magnetization transfer (qMT). We predicted the biggest training effects in MPF, because of its greater sensitivity to myelin, compared to diffusion measures. Changes were studied in WM pathways linking the putamen and the supplementary motor area (SMA-Putamen), and within three segments of the corpus callosum (CCI, CCII, CCIII). Tracts were reconstructed using deterministic tractography. Baseline MPF differences between patients and controls were also assessed with tract-based spatial statistics (TBSS), to inspect HD-associated changes in apparent myelination. Results: A reduction in baseline MPF was present in the mid section of the CC in HD group compared to controls. No significant training-associated changes were detected in FA, RD or Fr. However, after the drumming intervention, we detected increases in MPF in HD patients relative to healthy controls in the CCII, CCIII, and the right SMA-putamen. Furthermore patients improved their drumming and their executive function performance relative to controls increased after training. These behavioural changes did not correlate with the microstructural changes, suggesting that these processes follow different time courses. Conclusions: Drumming training improves motor and executive performance in HD and is associated with increases in apparent WM myelin. Tailored behavioural stimulation may lead to neural benefits in early HD that could be exploited for delaying disease progression.
