Corticospinal axon responses to different current directions induced by TMS in anesthetized macaques

When applied over the primary motor cortex (M1), transcranial magnetic stimulation (TMS) generates repetitive corticospinal volleys; the earliest is caused by direct (D) corticospinal stimulation; later indirect (I) waves likely arise from transsynaptic activation. A figure-of-eight coil can focus stimulation to a small cortical region. Changing the induced current direction may allow preferential stimulation of different waves, but there is little empirical evidence on the underlying single cell mechanisms. We examined the responses to focal TMS over M1 of 249 corticospinal axons recorded at C5 in six anesthetized monkeys. D, early indirect (I1) and late I-waves could all be generated by TMS with both posterior-anterior (PA) and anterior-posterior (AP) induced currents. However, at moderate intensities, PA stimulation selectively generated D-waves, and AP generated late I-waves. Most axons only responded within one latency window (D, I1 or late I) to either orientation; the number responding in multiple windows grew with increasing intensity, especially for AP stimulation. Axon conduction velocity had no effect on response probability, except for axons responding to AP TMS at late I latency which had significantly faster conduction velocity than those without late I responses. These results provide fine-grain details of how focal TMS activates the corticospinal tract.