EEG-timed neuromuscular stimulation shapes ipsilateral TMS-evoked motor responses in humans.

Objective: Sensorimotor beta activity provides a real-time marker of motor-network state, but whether electroencephalography (EEG)-derived timing of peripheral stimulation can modulate ipsilateral motor output remains unclear. We tested whether EEG-timed neuromuscular electrical stimulation (NMES) alters ipsilateral transcranial magnetic stimulation (TMS)-evoked motor responses in humans. Methods: Twenty right-handed healthy participants completed four sessions of 24 Hz NMES applied to the left extensor digitorum communis. NMES train onset was triggered at four nominal timing conditions derived from the ongoing 24 Hz EEG component over the ipsilateral sensorimotor cortex. Ipsilateral motor output was assessed with TMS before and after each intervention. Peak-to-peak amplitudes of ipsilateral TMS-evoked motor responses were analyzed using a linear mixed-effects model. Results: EEG-timed NMES produced timing-dependent and muscle-specific changes in ipsilateral TMS-evoked motor response amplitudes. Flexor responses were suppressed across timing conditions, whereas extensor responses increased selectively in one EEG-derived timing condition. This response pattern dissociated generalized antagonist suppression from timing-specific facilitation of the stimulated extensor motor output. Conclusions: Ipsilateral TMS-evoked motor responses are sensitive to the temporal alignment between peripheral input and ongoing EEG-recorded ipsilateral sensorimotor activity. Significance: EEG-timed NMES provides a human neurophysiological framework for probing state-dependent sensorimotor coupling and may inform future closed-loop peripheral neuromodulation strategies.