Inhibitory Effect of Subthreshold TMS on the Long-Latency Response in the Flexor Carpi Radialis

The corticospinal pathway and several secondary motor pathways contribute to long-latency responses(LLRs). While evidence of the contribution of secondary motor pathways to LLRs is available, it is unknown if these pathways can produce LLRs independently from corticospinal input. Transcranial magnetic stimulation(TMS) can modulate corticospinal excitability during the LLR. Subthreshold TMS would be ideal for inhibition of corticospinal excitability as it would allow to study function of secondary motor pathways using functional imaging methods with low temporal resolution with minimal activation confound. However, the subthreshold TMS parameters that maximally inhibit corticospinal activity are unknown. In this study, twenty-four participants performed a protocol that combined surface electromyography(EMG), robot-evoked wrist perturbations, and subthreshold TMS applied to the motor cortex to study the effect of TMS intensity and latency on the LLR amplitude in the flexor carpi radialis. We tested two TMS intensities of 90% and 95% AMT and three different latencies, defined such that the motor evoked potential (MEP) peak would arrive at 0 ms, 20 ms, or 50 ms prior to perturbation onset (T ₁ , T ₂ , T ₃ , respectively). Subthreshold TMS significantly reduced the LLR amplitude when applied with T ₂ ( p _adj = 0.0330) and T ₃ latencies ( p _adj = 0.0002). Overall, our findings indicate that single-pulse, subthreshold TMS delivered to evoke an MEP with timing comprised between 20 ms and 50 ms prior to perturbation onset significantly reduce the corticospinal component of the LLR. The outcome of this work can be used to inform functional neuroimaging protocols to study the causal role of secondary motor pathways on LLRs.