Disinhibition across secondary motor cortical regions during motor sequence learning: A TMS-EEG study.

Secondary motor cortical regions, such as the supplementary motor area (SMA) are involved in planning and learning motor sequences, however the neurophysiological mechanisms across these secondary cortical networks remain poorly understood. 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). Here, we investigated whether disinhibition occurs across secondary motor cortical regions during motor sequence learning using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG). Twenty-nine healthy adults (14 female) practiced a sequential motor task with TMS applied to the SMA during sequence planning. TMS-evoked potentials (TEPs) were measured with EEG before, during, and after practice. The N45 TEP peak was our primary measure of disinhibition, while we analysed the slope of aperiodic EEG activity as an additional E:I balance measure. We observed a reduction in N45 amplitudes across an electrode cluster encompassing the SMA and nearby cortical regions as participants began learning new motor sequences, compared to a baseline rest phase ( < .01). Smaller N45 amplitudes during early learning were associated with improvements in reaction times across learning ( < .01). Intriguingly, aperiodic exponents increased as learning progressed, and were associated with greater improvements in skill ( < .05). Overall, our results show that inhibition is modulated across SMA and secondary motor cortex during the planning phase of motor sequence learning, and thus provide novel insight on the neurophysiological mechanisms within higher-order motor cortex that accompany new sequence learning. Learning new motor sequences plays an important role in daily life, underpinning our capacity to write, type, or play complex music or sport. Coordinated activity across secondary motor cortical regions including the supplementary motor area is important for sequence learning, but the neurophysiological mechanisms across these regions associated with learning are unclear. A mechanism frequently documented in primary motor cortex during early learning is a reduction in inhibitory signalling, or disinhibition. Here, we observed disinhibition across electrodes clustered around the supplementary motor area as participants began learning novel motor sequences. Our findings broaden current understanding of the cortical mechanisms that accompany the encoding of new motor sequences, suggesting that these mechanisms are similar across primary and higher-order motor cortical regions.