Introduction: Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the contralesional primary motor cortex (M1) can promote upper limb recovery after stroke. Predictors of treatment responsiveness and underlying neurophysiological mechanisms remain unclear. We investigated whether efficacy of contralesional inhibitory rTMS depends on the baseline functional status of the ipsilesional corticospinal tract and whether treatment effects are mediated by changes in ipsilesional corticospinal excitability and motor-eloquent area (MEA) remapping. Methods: We analyzed secondary outcomes of the B-STARS trial, a randomized controlled trial on contralesional continuous theta-burst stimulation (cTBS), an inhibitory form of rTMS, to promote upper limb recovery after stroke. Sixty patients receiving either active cTBS (n=29) or sham cTBS (n=31) were included. Patients were classified as motor-evoked potential (MEP)-positive or -negative based on the presence or absence of MEPs in response to TMS at baseline. Corticospinal excitability and upper limb outcome were measured from TMS-based resting motor threshold assessment and the Action Research Arm Test (ARAT) score, respectively, before cTBS treatment and at six follow-up visits up to one year after stroke. Forty-four patients also underwent longitudinal navigated TMS-based motor mapping to assess MEA remapping from longitudinal changes in MEA overlap. Results: Baseline MEP status was associated with cTBS treatment efficacy on the ARAT within twelve hours (mean difference (MD) 11.3; 95% confidence interval (CI 0.8 to 21.9; p 0.036) and at one month post-treatment (MD 19.9; 95% CI 5.2 to 34.7; p 0.008) and at three months post-stroke (MD 20.3; 95% CI 3.6 to 37.1; p 0.018). Ipsilesional corticospinal excitability was similar in the active and sham cTBS groups. MEA overlap was 27% (95% CI -44 to -11; p 0.003), 25% (95% CI -45 to -5; p 0.022) and 29% (95% CI -48 to -11; p 0.004) less in the active cTBS group compared to the sham group at the above-mentioned time points, respectively. Conclusions: Efficacy of contralesional cTBS treatment in promoting upper limb recovery after stroke depends on baseline functional status of the ipsilesional corticospinal tract and may be mediated by an increase in MEA remapping.
Vink et al. (2026) studied this question.
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