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 (p < .01). Smaller N45 amplitudes during early learning were associated with improvements in reaction times across learning (p < .01). Intriguingly, aperiodic exponents increased as learning progressed, and were associated with greater improvements in skill (p < .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.Significance Statement 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.

中文翻译：

---

运动序列学习过程中次级运动皮层区域的去抑制：TMS-EEG 研究。


次级运动皮层区域，例如辅助运动区 （SMA） 参与规划和学习运动序列，但这些次级皮层网络的神经生理机制仍然知之甚少。在初级运动皮层中，兴奋性和抑制性神经传递 （E：I 平衡） 的变化伴随着运动序列学习。特别是，抑制（即去抑制）的早期减少。在这里，我们研究了在使用经颅磁刺激 （TMS） 和脑电图 （EEG） 相结合的运动序列学习过程中，次级运动皮层区域是否发生去抑制。29 名健康成人 （14 名女性） 在序列规划期间将 TMS 应用于 SMA 练习顺序运动任务。在练习前、练习中和练习后用脑电图测量 TMS 诱发电位 （TEP）。N45 TEP 峰值是我们去抑制的主要衡量标准，而我们分析了非周期性脑电图活动的斜率作为额外的 E：I 平衡衡量标准。与基线休息期相比，当参与者开始学习新的运动序列时，我们观察到包含 SMA 和附近皮质区域的电极簇的 N45 振幅降低 （p < .01）。早期学习期间较小的 N45 振幅与整个学习过程中反应时间的改善有关 （p < .01）。有趣的是，非周期性指数随着学习的进行而增加，并且与技能的更大提高有关 （p < .05）。总体而言，我们的结果表明，在运动序列学习的规划阶段，SMA 和次级运动皮层的抑制受到调节，从而为伴随新序列学习的高阶运动皮层内的神经生理机制提供了新的见解。意义陈述 学习新的运动序列在日常生活中起着重要作用，支撑着我们编写、打字或播放复杂音乐或运动的能力。包括辅助运动区在内的次级运动皮层区域的协调活动对于序列学习很重要，但这些区域与学习相关的神经生理机制尚不清楚。在早期学习期间，初级运动皮层中经常记录的一种机制是抑制信号或去抑制的减少。在这里，当参与者开始学习新的运动序列时，我们观察到聚集在辅助运动区域周围的电极的去抑制。我们的研究结果拓宽了当前对伴随新运动序列编码的皮层机制的理解，表明这些机制在初级和高阶运动皮层区域是相似的。