Post-stroke changes in the ipsilesional motor area after contralesional continuous theta-burst stimulation

BackgroundInhibitory repetitive transcranial magnetic stimulation (rTMS) of the contralesional primary motor cortex (M1) can promote upper limb recovery after stroke. However, its working mechanism remains unclear. We hypothesised that contralesional inhibitory rTMS increases ipsilesional M1 excitability and promotes ipsilesional motor-eloquent area (MEA) remapping. MethodsSixty patients who participated in a trial on contralesional continuous theta-burst stimulation (cTBS), an inhibitory form of rTMS, for the promotion of upper limb recovery after stroke, were included. M1 excitability and upper limb function were measured from TMS-based resting motor thresholds (RMTs) and the Fugl-Meyer Assessment (FMA) arm score, respectively, before cTBS treatment and at six follow-up visits up to one year after stroke. Forty-four patients additionally underwent longitudinal navigated TMS-based motor mapping. Remapping of the MEA was assessed from longitudinal changes in MEA overlap. Outcomes were analysed using mixed models for repeated measures. ResultsThe ipsilesional RMT was 11% lower after active cTBS compared to sham cTBS (95% CI -18.7 to -2.6; p 0.0099) within twelve hours after the series of treatments. Compared to the sham cTBS group, MEA overlap was 27% (95% CI -44 to -11; p 0.0030), 25% (95% CI -45 to -5; p 0.0224) and 29% (95% CI -48 to -11; p 0.0038) less in the active cTBS group within twelve hours and at one week post-treatment, and three months post-stroke, respectively. Ipsilesional M1 excitability (i.e., RMT) within twelve hours post-cTBS correlated with FMA arm score at 3 months post-stroke (Spearmans rho 0.59; p < 0.0001). ConclusionsUpper limb recovery after cTBS treatment of the contralesional M1 after stroke may be caused by increased ipsilesional M1 excitability and MEA remapping. Trial registrationhttps://trialsearch.who.int/; Unique identifier: NTR6133.