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.

Macromolecular Proton Fraction as a Myelin Biomarker: Principles, Validation, and Applications

“…MPF decrease in whole-brain WM (Bourbon-Teles et al, 2019;Casella et al, 2020). Motor training induced a significant MPF increase in the corpus callosum and motor pathways (Casella et al, 2020).…”

Protocol for a randomised controlled feasibility trial of HD-DRUM, a rhythmic movement training application for cognitive and motor symptoms in people with Huntington’s disease

“…The HD-DRUM app is a computerised version of the drumming training intervention we have previously devised 19 20 . A detailed description of HD-DRUM according to the template for intervention description and replication (TIDieR) 24 has been published 21 .…”

“…Previously, we explored eight weeks of ∼15 minutes of bongo drumming five times per week as a therapeutic tool for people with HD 19 20 . We observed performance improvements in executive function tasks and changes in WM microstructural measurements (including an estimate of myelin) of callosal and cortico-putamen connections 19 20 .…”

“…Previously, we explored eight weeks of ∼15 minutes of bongo drumming five times per week as a therapeutic tool for people with HD 19 20 . We observed performance improvements in executive function tasks and changes in WM microstructural measurements (including an estimate of myelin) of callosal and cortico-putamen connections 19 20 . Although these initial pilot results are promising, they are preliminary in nature and necessitate validation through a fully powered randomised controlled trial (RCT).…”

Differences in white matter detected byex vivo9.4T MRI are associated with axonal changes in the R6/1 model of Huntington’s Disease

“…It is therefore a research priority to enhance understanding of how it develops and identify biomarkers to support therapy development. Recent investigations in HD have recognized alterations in the brain's white matter (WM) as relevant pathophysiological feature of HD [1][2][3][4][5][6][7][8][9][10][11][12] . Specifically, WM atrophy has been shown both in animal models and in human HD carriers by histopathological post-mortem studies [13][14][15][16][17] , and MRI studies 2,4,5,11,[17][18][19][20][21] .…”