Motor cortical (M1) transcranial magnetic stimulation (TMS) interventions increase corticospinal output and improve motor learning when delivered during sensorimotor mu rhythm trough but not peak phases, suggesting that the mechanisms supporting motor learning may be most active during mu trough phases. Based on these findings, we predicted that motor sequence learning-related corticospinal plasticity would be most evident when measured during mu trough phases. Healthy adults were assigned to either a sequence or random group. Participants in the sequence group practiced the implicit serial reaction time task (SRTT), which contained an embedded, repeating 12-item sequence. Participants in the random group practiced a version of the SRTT that contained no sequence. We measured mu phase-independent and mu phase-dependent MEP amplitudes using EEG-informed single-pulse TMS before, immediately, and 30 minutes after the SRTT in both groups. All participants performed a retention test one hour after SRTT acquisition. In both groups, mu phase-independent MEP amplitudes increased following SRTT acquisition, but the pattern of mu phase-dependent MEP amplitude increases after SRTT acquisition differed between groups. Relative to the random group, the sequence group showed greater increases in peak-specific corticospinal output 30 minutes after SRTT acquisition. Contrary to our original hypothesis, results revealed that motor sequence learning recruits peak-rather than trough-specific neurophysiological mechanisms. These findings suggest that mu peak phases may provide protected time windows for motor memory consolidation and demonstrate the presence of a mu phase-dependent motor learning mechanism in the human brain.
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