Motor sequence learning elicits mu peak-specific corticospinal plasticity

Abstract 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 no-sequence 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 no-sequence 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 after, 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 changes after SRTT acquisition differed between groups. Relative to the no-sequence group, the sequence group showed greater peak-specific MEP amplitude increases 30 minutes after SRTT acquisition. Further, the magnitude of these peak-specific MEP amplitude increases was negatively associated with the magnitude of sequence-specific learning. Contrary to our original hypothesis, results revealed that motor sequence-specific learning elicits peak-specific corticospinal plasticity. Findings provide first direct evidence for the presence of a mu phase-dependent motor learning mechanism in the human brain. New and Noteworthy Recent work suggests that motor learning’s neural mechanisms may be most active during specific sensorimotor mu rhythm phases. If so, motor sequence learning-induced corticospinal plasticity should be more evident during some mu phases than others. Our results show that motor sequence-specific learning elicits corticospinal plasticity that is most prominent during mu peak phases. Further, this peak-specific plasticity correlates with learning. Findings establish the presence of a mu phase-dependent motor learning mechanism in the human brain.