Feasibility Study of Supplementary Motor Area to Primary Motor Cortex Facilitation using Multi-locus Transcranial Magnetic Stimulation.

The connectivity between the supplementary motor area (SMA) and the primary motor cortex (M1) is critical for motor preparation and execution, mediated by direct glutamatergic pathways. The facilitation of M1 by SMA through paired-pulse transcranial magnetic stimulation (TMS) has been studied using conventional dual-coil setups, which face challenges in spatial precision, reproducibility, and participant comfort. This feasibility study introduces a novel application of multi-locus TMS (mTMS) for SMA-M1 paired-pulse facilitation, enabling accurate and reproducible stimulation without manual coil adjustments. A healthy participant underwent TMS experiments informed by task-based functional magnetic resonance imaging for precise SMA localization and electric field simulations for optimized targeting. Causality of SMA-M1 facilitation was examined across three SMA targets, using interstimulus intervals (ISIs) of 6, 7, and 8 ms, with electromyography recorded from three hand muscles to evaluate effects on the motor evoked potential (MEP) responses.We observed ISI- and SMA target-dependent facilitation. The 8-ms ISI resulted in the strongest MEP facilitation across most conditions, emphasizing the fine temporal dependency. SMA target location also appeared to modulate the MEP facilitation. The abductor digiti minimi muscle exhibited the most consistent facilitation and lowest MEP amplitude variability compared to the other muscles. These findings underline the importance of spatial and temporal precision in probing SMA-M1 causal couplings. Future work with larger sample sizes and multimodal imaging are needed to optimize stimulation parameters and further explain the detailed neurophysiological mechanism of SMA-M1 connectivity.Clinical Relevance- This study demonstrates the feasibility of mTMS to quantify SMA-M1 facilitation. This innovation has potential implications for developing targeted neuromodulation therapies in motor-related neurological disorders such as Parkinson's disease and Tourette syndrome, where SMA-M1 connectivity is often impaired.