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). However, it is unknown if secondary 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, thirty-six healthy participants performed a protocol combining surface electromyography(EMG), robot-evoked wrist perturbations, and single pulse TMS applied to the motor cortex to study the effect of TMS intensity and latency on the LLR amplitude in the flexor carpi radialis. In one experiment, we tested two TMS intensities of 90% and 95% of the active motor threshold and three 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). In a second experiment, we sought to determine whether the inhibitory effect of subthreshold TMS was specific to long-latency responses. TMS significantly reduced the LLR amplitude when applied with T_3 latency, even when restricting the analysis to stimulation modes that did not induce a motor-evoked response (padj=0.005). However, we found no evidence that TMS inhibition was specific to the LLR. Overall, our findings indicate that single-pulse, subthreshold TMS significantly reduces the corticospinal component of the LLR.