Objective: To determine the best timing for non-invasive brain stimulation (NIBS) intervention to enhance physiotherapy-induced motor recovery in patients with Parkinson’s disease (PwPD), and to define a dose-response relationship.

Background: Solid evidence suggests that physiotherapy (PT) is effective in treating motor symptoms of PD^1,2. Additionally, an increased recovery effect was found when administered together with NIBS techniques³. However, the optimal timing of NIBS intervention with respect to PT is still unclear⁴.

Method: The literature search was conducted in PubMed/MEDLINE, Embase, and Web of Science in December 2024. Guidelines were followed throughout the process4,5. We considered only randomized clinical trials (RCTs) or crossover studies assessing the effects of NIBS + PT interventions on motor outcomes in PwPD. We conducted a random effects meta-analysis to assess the overall effect of the intervention, and a subgroup analysis considering the timing of NIBS with respect to physiotherapy administration (before, during), and the PT intervention. Lastly, we performed a meta-regression to identify dose-response predictors.

Results: From 1102 studies, 16 RCTs and 3 crossover studies were included, for a total of 525 PwPD (mean ± SD: age, 68±4.18; H&Y, 1.89±0.33; MDS-UPDRS III, 34.8±7.42). Studies tested transcranial direct current stimulation (tDCS, n=16) and repetitive transcranial magnetic stimulation (rTMS, n=3), before (n=6) and during (n=10) PT, which was mainly walking training (n=9) and multiple exercise (n=4). The overall NIBS intervention showed a moderate pooled effect size (SMD=0.76; 95% CI 0.22-1.30, p<0.01). Only NIBS performed during (but not before) PT showed a moderate pooled effect size (SMD=0.84; 95% CI 0.19-1.48, p<0.01). Among treatments, only walking training showed a moderate pooled effect size (SMD=0.84; 95% CI 0.1-1.58, p<0.01). Motor improvement correlated positively with PT session (min, β=0.047, p=0.018), total time of NIBS and PT treatment (min – respectively, β=0.002, p=0.01; β=0.001, p=0.02), and the number of NIBS and PT sessions (n – respectively, β=0.045, p=0.04; β=0.046, p=0.04).

Conclusion: Current findings support the use of NIBS techniques to enhance motor recovery only during PT intervention, depending upon the duration of the interventions.

References: 1 van der Kolk NM, King LA. Effects of exercise on mobility in people with Parkinson’s disease. Movement Disorders 2013; 28: 1587–96.
2 Goodwin VA, Richards SH, Taylor RS, Taylor AH, Campbell JL. The effectiveness of exercise interventions for people with Parkinson’s disease: a systematic review and meta-analysis. Movement disorders : official journal of the Movement Disorder Society 2008; 23: 631–40.
3 Harris DM, Latella C, Tripodi N, O’Bryan SJ. Exploring Non-invasive Brain Stimulation Effects on Physical Outcomes in People With Parkinson’s Disease: An Umbrella Evidence Mapping Review With Meta-analyses. Neurorehabil Neural Repair 2025; : 15459683241310984.
4 Nguyen TXD, Mai PT, Chang Y-J, Hsieh T-H. Effects of transcranial direct current stimulation alone and in combination with rehabilitation therapies on gait and balance among individuals with Parkinson’s disease: a systematic review and meta-analysis. Journal of NeuroEngineering and Rehabilitation 2024; 21: 27.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-impact-of-non-invasive-brain-stimulation-timing-on-physiotherapy-outcomes-for-parkinsons-disease-a-systematic-review-with-dose-response-analysis/