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Randomized Controlled Trial
. 2025 Oct;39(10):801-813.
doi: 10.1177/15459683251351883. Epub 2025 Jul 10.

Modulating Brain Excitability with Cardiovascular Exercise in Chronic Stroke: A Randomized Controlled Trial

Lynden Rodrigues  1   2 , Kevin Moncion  3 , Bernat De Las Heras  1   2 , Jacopo Cristini  1   2 , Roya Khalili  1   2 , Janice J Eng  4 , Joyce Fung  1   2 , Marilyn MacKay-Lyons  5 , Alexander Thiel  6 , Ada Tang  3 , Marc Roig  1   2
Affiliations
Randomized Controlled Trial

Modulating Brain Excitability with Cardiovascular Exercise in Chronic Stroke: A Randomized Controlled Trial

Lynden Rodrigues et al. Neurorehabil Neural Repair. 2025 Oct.

Abstract

Background: Corticospinal excitability (CSE) is a surrogate measure of neuroplasticity within the corticospinal tract measured with transcranial magnetic stimulation (TMS). A single bout of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) cardiovascular exercise (CE) have been both demonstrated to transiently augment CSE in people with stroke. However, the effect of multiple sessions of CE and exercise intensity is unknown.

Objectives: We conducted a randomized controlled trial (NCT03614585) to examine the effect of a HIIT vs. MICT CE program on CSE measures obtained using TMS applied on the ipsilesional (ILH) and contralesional (CLH) hemispheres.

Methods: Fifty-six individuals with cortical and/or subcortical stroke lesions in the chronic phase of stroke recovery (>6 months) were randomly assigned to a 12-week HIIT (n = 28) or MICT (n = 28) program. CSE measures were obtained at baseline and post-intervention. Linear mixed model analyses were conducted to compare changes in CSE measures and their respective interhemispheric ratios.

Results: CSE changes were not significantly different between HIIT and MICT but exploratory analyses showed that, when analyzed together, both groups increased resting motor evoked potential (MEP) amplitude (P = .003), decreased resting motor threshold (rMT) (P = .030), and reduced intracortical facilitation (ICF) (P = .049) in the ILH. No CSE changes in the CLH were observed. HIIT and MICT rebalanced interhemispheric rMT (P = .020) and ICF ratios (P = .040), and increased resting MEP amplitude ratio (P = .020).

Conclusions: Chronic CE increases excitatory ILH CSE measures and reduces interhemispheric imbalances but intensity does not have a moderating effect. More studies are needed to determine the functional relevance of exercise-induced changes in CSE in post-stroke recovery.

Keywords: GABA; brain excitability; cardiovascular exercise; glutamate; stroke; transcranial magnetic stimulation.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Flow chart of the randomized controlled trial. Abbreviations, n, number of participants; TMS, transcranial magnetic stimulation; ILH, ipsilesional hemisphere; CLH, contralesional hemisphere; SICI, short-interval intracortical inhibition; ICF, intracortical facilitation; HIIT, high-intensity interval training; MICT, moderate-intensity continuous training; T0, baseline; T1, post-intervention.
Figure 2.
Figure 2.
Change in cortico-spinal excitability T0-T1. (A) Resting MEP amplitude. (B) Active MEP amplitude. (C) Resting Motor Threshold. (D) Cortical Silent Period. (E) Intracortical Facilitation. (F) Short-interval Intracortical Inhibition. Abbreviations: MEP, Motor Evoked Potential; CLH, contralesional hemisphere; ILH, ipsilesional hemisphere; HIIT, high-intensity interval training; MICT, moderate-intensity continuous training; T0, baseline; T1, post-intervention; mV, millivolts; %MSO, percentage of maximum stimulator output; F, Facilitation; I, Inhibition. +Indicates significant time effect (P < .05) according to linear mixed model. *Indicates significant within-group differences according to pairwise comparisons. Bars are estimates of means and error bars are standard errors of the estimates. (E and F) Values <100 indicate inhibition of conditioned MEP.
Figure 3.
Figure 3.
Interhemispheric ratios T0-T1. (A) Resting MEP amplitude. (B) Active MEP amplitude. (C) Resting Motor Threshold. (D) Cortical Silent Period. (E) Intracortical Facilitation. (F) Short-interval Intracortical Inhibition. Abbreviations: ILH/CLH, Interhemispheric ratio between ipsilesional and contralesional hemisphere; MEP, motor evoked potential; HIIT, high-intensity interval training; MICT, moderate-intensity continuous training; T0, baseline; T1, post-intervention. +Indicates significant time effect (P < .05) according to linear mixed model. *Indicates significant within-group differences according to pairwise comparisons. Data points are estimates of means and error bars are standard errors of the estimates. Values > 1.0 indicate ILH:CLH ratios favoring ILH.
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