Fluctuations in the optimal sensorimotor mu-rhythm phase associated with high corticospinal excitability during TMS-EEG.

Background: Transcranial magnetic stimulation (TMS) applied to the primary motor cortex (M1) targeting the sensorimotor mu-rhythm trough phase has been associated with higher corticospinal excitability than during the peak phase, as measured by the amplitude of motor evoked potentials (MEP). However, this phase-dependent effect varies across studies and individuals.

Objectives: To explore the stability of the mu-phase effect. We investigated potential inter- and intrasession fluctuations in the optimal mu-phase associated with high corticospinal excitability.

Methods: We applied brain state-independently 800 single TMS pulses to left M1 in 60 participants. For the analysis, participants were classified into two groups based on the significance/insignificance of the phase effect. We assessed the stability of the optimal phase using entropy and a novel phase-MEP stability metric. We evaluated how well the MEP amplitude can be predicted from mu-phase, mu-power, and their interaction using a linear mixed effects model.

Results: Our results showed that, for the significant phase effect group only, phases around trough elicited significantly larger MEPs than at peak. The optimal phase varied in both groups, but remained primarily around the trough in participants with a significant phase effect. Mu-power positively correlated with MEP amplitudes in both groups. In a second experiment, 10 participants completed two sessions and showed low test-retest reliability of the mu-phase effect.

Conclusions: Our findings confirm that mu-phase and mu-power modulate corticospinal excitability. Individual inter-session variability and within-session fluctuations limit the generalizability of fixed-phase targeting. Future closed-loop TMS protocols may benefit from real-time adaptive algorithms to optimize stimulation efficacy.