Immediate cortical responses to transcranial magnetic stimulation of the human motor leg area

Abstract

Background Immediate transcranial evoked potentials (iTEPs) are ultra-early electroencephalographic responses elicited by single-pulse transcranial magnetic stimulation (TMS) of the primary motor cortical hand area (M1-HAND). Their characteristic latency, waveform, and sensitivity to short-interval intracortical inhibition suggest a close relationship to the cortical generators of indirect corticospinal volleys (I-waves). Here, we tested the hypothesis that iTEPs constitute a fundamental physiological response of human motor cortex and therefore generalize across motor representations, including the leg representation (M1-LEG). Methods Single-pulse TMS was delivered over the motor cortical representation of the right tibialis anterior (TA) in 16 healthy volunteers. In a subset of participants (n=10), stimulus–response curves and paired-pulse short-interval intracortical inhibition (SICI) measures were obtained. Results TMS of M1-LEG elicited reproducible iTEPs consisting of a slow positive deflection with superimposed high-frequency peaks with topographic maxima in electrodes adjacent to the stimulation site. M1-LEG iTEPs emerged close to active motor threshold and increased in prevalence and amplitude with increasing stimulation intensity. Paired-pulse stimulation produced consistent SICI of the second and third iTEP peaks. M1-LEG stimulation also evoked conventional later TEPs with latencies and polarities closely resembling those recorded after M1-HAND stimulation. Conclusions TMS of the human M1-LEG elicits robust iTEPs that closely resemble those recorded from M1-HAND in their timing, intensity dependence, and sensitivity to intracortical inhibition. These findings indicate that iTEPs are not specific to M1-HAND but reflect a general physiological response of human motor cortex closely linked to corticospinal I-wave generation. This broadens their utility as a non-invasive probe of excitatory and inhibitory circuit dynamics throughout the human motor system. Highlights Single-pulse TMS of the leg motor cortex (M1-LEG) elicits reproducible immediate TMS-evoked potentials (iTEPs). M1-LEG iTEPs emerge near active motor threshold, increase with stimulation intensity, and display selective short-interval intracortical inhibition of late iTEP peaks with paired-pulse TMS. Immediate and later TMS-evoked responses show striking resemblance in leg and hand motor cortex. The shared properties of M1-LEG and M1-HAND iTEPs support iTEPs as a general motor cortex response linked to corticospinal I-wave generation and intracortical inhibition.