Disrupting motor cortical regional activity during motor sequence skill training impairs human motor visuomotor skill acquisition and learning that is not sequence-specific

Implicit sequence and visuomotor skill learning is important for successful goal-directed behavior in everyday tasks. However, prior research has primarily relied on correlational methods to investigate the underlying neural mechanisms of sequence and visuomotor skill learning. To evaluate the necessary contributions of different motor cortical regions to both types of skill learning, we enrolled 62 neurotypical adults (41 female, 21 male) and delivered spatiotemporally resolved single-pulse transcranial magnetic stimulation (TMS) over either the premotor cortex (PMC) or primary motor cortex (M1) to transiently disrupt activity while participants practiced an implicit motor sequence task. We hypothesized that 1) PMC disruption would preferentially reduce sequence-specific skill acquisition (Experiment 1) and retention (Experiment 2) while 2) M1 disruption would diminish visuomotor skill acquisition and retention but not sequence learning. Our results demonstrated that TMS-based interference over both M1 and PMC did not disrupt implicit sequence-specific motor skill learning after training however, it did disrupt visuomotor skill acquisition and total learning that was not sequence-specific. Further, disruption of PMC activity had a greater effect on reducing visuomotor skill learning than M1 supporting a potentially distinct role of the PMC in the early stages of skill learning. Significance Statement: Determining which brain areas are required for motor sequence learning is crucial to understanding goal-directed behaviors in everyday life. However, the causal contributions of regional brain activity to implicit sequence learning are poorly understood. Here we used single-pulse transcranial magnetic stimulation (TMS), a form of noninvasive brain stimulation, to interfere with activity in either premotor (PMC) or primary motor (M1) cortex during implicit motor sequence learning. Our results highlight that both regions are engaged during learning and that PMC may play a unique role in general visuomotor acquisition and may contribute to sequence-specific skill learning. Study findings could contribute to identifying of neural biomarkers necessary to develop precise and personalized neuromodulation strategies for enhancing of motor skill learning and/or recovery.