Motor cortex plasticity response to acute cardiorespiratory exercise and intermittent theta-burst stimulation is attenuated in premanifest and early Huntington\u2019s disease

Dylan Curtin,Julie C Stout,Sophie C Andrews,James P Coxon

doi:10.1038/s41598-021-04378-2

Dylan Curtin, Julie C Stout + Show 2 more

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https://doi.org/10.1038/s41598-021-04378-2

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Abstract

Huntington’s disease (HD) mouse models suggest that cardiovascular exercise may enhance neuroplasticity and delay disease signs, however, the effects of exercise on neuroplasticity in people with HD are unknown. Using a repeated-measures experimental design, we compared the effects of a single bout of high-intensity exercise, moderate-intensity exercise, or rest, on motor cortex synaptic plasticity in 14 HD CAG-expanded participants (9 premanifest and 5 early manifest) and 20 CAG-healthy control participants, using transcranial magnetic stimulation. Measures of cortico-motor excitability, short-interval intracortical inhibition and intracortical facilitation were obtained before and after a 20-min bout of either high-intensity interval exercise, moderate-intensity continuous exercise, or rest, and again after intermittent theta burst stimulation (iTBS). HD participants showed less inhibition at baseline compared to controls. Whereas the control group showed increased excitability and facilitation following high-intensity exercise and iTBS, the HD group showed no differences in neuroplasticity responses following either exercise intensity or rest, with follow-up Bayesian analyses providing consistent evidence that these effects were absent in the HD group. These findings indicate that exercise-induced synaptic plasticity mechanisms in response to acute exercise may be attenuated in HD, and demonstrate the need for future research to further investigate exercise and plasticity mechanisms in people with HD.

Highlights

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease resulting in motor dysfunction, cognitive impairment and neuropsychiatric symptoms[1]
The HD and control groups were similar in terms of baseline resting and active motor cortex thresholds, and facilitation (ICF), with no significant main effects of Group or Session, and no interaction effects (Table 1 displays main effects of Group results for these variables)
We examined the effect of exercise on corticomotor excitability (CME) by normalizing the average postiTBS MEP to the post-exercise time-point

Summary

Introduction

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease resulting in motor dysfunction, cognitive impairment and neuropsychiatric symptoms[1]. No study has investigated the acute effects of exercise on motor cortex plasticity in HD This is important because there is evidence that early disruption to cortico-striatal circuits reduces inhibition in the motor cortex[27], and previous studies have shown that people with the CAG-expansion for HD have attenuated plasticity responses to several non-invasive brain stimulation protocols[28,29,30,31]. The aim of the current study was to investigate whether a single bout of either HIIT or moderate-intensity continuous exercise enhances the response to iTBS in people with premanifest and early manifest HD, in comparison to an HD-CAG healthy control group. An alternative hypothesis was that baseline alterations to motor cortex neurophysiology (e.g., reduced inhibition and increased facilitation) would attenuate this effect

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