Non-invasive Stimulation of Contralateral Primary Motor Cortex Reduces the Amount of Skill Generalization to the Untrained Arm

ABSTRACT Successfully learned motor skills can generalize or transfer to the untrained arm. The neural substrate underlying such intermanual/interlimb generalization of newly acquired skill memory is unclear. Here, we focused on contralateral primary motor cortex (cM1) which is considered a key brain area for skill learning and memory consolidation. We probed the causal role of cM1 in intermanual skill generalization in a two-day study involving right-handed young individuals (n=31) who learned a novel motor skill reaching task. Immediately following (right-arm) learning, we delivered low-frequency (1Hz, 1800 pulses) repetitive transcranial magnetic stimulation (rTMS) to target left cM1 in one group of individuals (n=15), while another group (n=16) served as an active control in which ipsilateral M1 (iM1) was targeted. On the same day we measured corticospinal excitability (CSE) to assess learning-induced and rTMS-induced neuroplastic changes occurring in the targeted M1s. Next day after 24-hours, both groups were tested for intermanual skill generalization (left-arm), followed by a brief test of intralimb retention (right-arm). Our results show that stimulating cM1, versus iM1, reduced the amount of generalization to the untrained arm on the next day, without affecting its (re)learning ability or the follow-up retention performance of the trained arm. Further, rTMS stimulation induced a net facilitation in CSE- with higher facilitation tending to correlate to lower generalization in a subset of high learners in cM1 group. Taken together, this study highlights the role of cM1 in skill generalization such that it seems to mediate the early transfer of learning to the untrained arm. NEW AND NOTEWORTHY Intermanual skill generalization from trained to the untrained arm is causally mediated by the contralateral (trained) primary motor cortex (cM1) as opposed to the ipsilateral (untrained) motor cortex. Low-frequency stimulation of M1 in our study led to a facilitation of corticospinal excitability, while impairing the amount of skill generalization in the cM1 group. This highlights a rather paradoxical and opposite effect of non-invasive brain stimulation, such as rTMS, on motor behavior and associated motor excitability. Our data also suggest involvement of additional brain areas for such motor skill behavior that were rendered unperturbed by rTMS in this case and, thus, contributed to an overall positive skill performance achieved by both arms the next day.