Supplementary motor area disinhibition during motor sequence learning: A TMS-EEG study

Abstract Background In primary motor cortex, changes in excitatory and inhibitory neurotransmission (E:I balance) accompany motor sequence learning. In particular, there is an early reduction in inhibition (i.e., disinhibition). The supplementary motor area (SMA) is a key brain region involved in the learning of sequences, however the neurophysiological mechanisms within SMA which support motor sequence learning remain poorly understood. Disinhibition may also occur in SMA, but this possibility remains unexamined. Objective We investigated disinhibition within SMA during motor sequence learning using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG). Methods Twenty-nine healthy adults practiced a sequential motor task. TMS-evoked potentials (TEPs) resulting from SMA stimulation were measured with EEG before, during, and after practice. The N45 TEP peak was our primary measure of disinhibition. Furthermore, the slope of aperiodic EEG activity was included as an additional E:I balance measure. Results Significant improvements in task performance (i.e., learning) occurred with practice. We observed smaller N45 amplitudes during early learning relative to baseline (both p < .01), indicative of disinhibition. Intriguingly, aperiodic exponents increased as learning progressed and were associated with greater sequence learning ( p < .05). Conclusion Our results show disinhibition within SMA during the planning phase of motor sequence learning and thus provide novel understanding on the neurophysiological mechanisms within higher-order motor cortex that accompany new sequence learning.