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bioRxiv · 10.1101/2025.10.28.685170

Dissociable Roles of Primary Motor and Supplementary Motor Cortex in Shaping the Neural Drive to Muscle

Escalante, Y.·Lei, Y.
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Abstract

The primary motor cortex (M1) and supplementary motor area (SMA) are critical for motor execution and planning, yet their distinct causal contributions to modulating the neural drive to muscles remain incompletely understood. To dissociate their roles, we applied inhibitory transcranial magnetic stimulation (TMS) over M1, SMA, or a sham condition in 72 healthy participants and characterized the activity of single motor units from high-density EMG recorded during a sustained isometric contraction. Our results revealed a clear functional divergence. M1 inhibition produced a direct failure of motor output, causing a rapid force decline compared to sham, which was strongly correlated with a reduction in motor unit firing rates. Conversely, SMA inhibition did not impair net force. Instead, it altered the fundamental structure of the motor command, compelling a compensatory strategy characterized by a reliance on smaller-amplitude motor units with lower firing rates and a marked degradation of the low-frequency (delta-band) coherence that organizes stable output. These results provide direct causal evidence that M1 directly dictates the magnitude of motor output via population firing rates, while SMA orchestrates the composition and temporal structure of the active motor unit pool to generate an efficient and stable command. Significance StatementUsing causal brain stimulation, we provide the first direct evidence that the primary motor cortex (M1) and supplementary motor area (SMA) serve distinct, non-redundant roles in controlling motor unit populations. We show that inhibiting M1 directly impairs force magnitude by reducing motor unit firing rates. In contrast, inhibiting SMA spares net force but disrupts the underlying motor plan, compelling a compensatory strategy that uses smaller motor units and degrades temporal firing organization via a loss of delta-band coherence. By demonstrating that M1 governs motor power while SMA organizes motor strategy, this study opens new avenues for personalizing neuro-rehabilitation to address the specific cortical origin of a patients motor deficits.

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Escalante, Y., Lei, Y.. 2025-10-30. Dissociable Roles of Primary Motor and Supplementary Motor Cortex in Shaping the Neural Drive to Muscle. https://doi.org/10.1101/2025.10.28.685170

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