Transcranial magnetic stimulation (TMS) is a noninvasive neuromodulation technique showing promise in stroke rehabilitation, with evidence indicating significant enhancement in motor function of...Show moreTranscranial magnetic stimulation (TMS) is a noninvasive neuromodulation technique showing promise in stroke rehabilitation, with evidence indicating significant enhancement in motor function of the contralateral limb following treatment. While TMS appears promising for stroke rehabilitation, there is variability in the level of improvement individuals exhibit. This variability may be attributed to oscillatory neurophysiology, which refers to the rhythmic electrical activity of the brain. Therefore, this study investigated phase-dependent changes in cortical excitability after TMS among stroke patients in affected and unaffected hemispheres. We investigated motor-evoked and TMS-evoked potentials at four phases of the ongoing motor cortical mu rhythm (trough, peak, rising, falling) in both hemispheres (affected, unaffected). Participants comprised N=11 chronic subcortical stroke patients (6 female, mean ± std age: 58 y ± 11.4) with affected lateralized upper-limb impairment. Four blocks of 150 TMS pulses were applied on each hemisphere, targeting the primary motor hotspot of the first dorsal interosseus muscle of the contralateral hand. Participants watched nature videos during stimulation to maintain consistent attention levels. Cortical excitability was assessed by analyzing motor-evoked potentials (MEP) and TMS-evoked potentials (TEP). Results showed that motor responses (measured through MEP amplitudes) were significantly larger at the trough and rising phase compared to the peak phase. No significant differences were observed between the affected and unaffected hemispheres. TEP components, the brain signals in response to TMS, did not exhibit significant phase-dependent changes. While our findings showed a nonsignificant effect of stroke severity, exploratory correlation analyses presented a positive association between higher remaining movement function and enhanced phase-dependent responses to TMS. The findings build upon previous research indicating phase-dependent changes in cortical excitability for MEPs but not for TEPs. The larger MEP amplitudes during trough and rising phases suggest that TMS can be more effective at specific points of cortical activity. Further exploration is needed to assess the efficacy of phase-specific TMS interventions in clinical settings, potentially through larger-scale clinical trials with longitudinal designs and comparative effectiveness studies, aiming to evaluate functional outcomes and determine their impact on motor recovery.Show less