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PreprintCC BY-NC-NDbioRxiv

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

  1. 1Danish Research Centre for Magnetic Resonance, Department of Radiology and Nuclear Medicine, Copenhagen University Hospital - Amager and Hvidovre, Kettegard All

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.

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BibTeX
@misc{beck2026immediate,
  title = {{Immediate cortical responses to transcranial magnetic stimulation of the human motor leg area}},
  author = {M. M. Beck and M. Nuyts and L. Sakalauskaite and J. Rothwell and H. R. Siebner and L. Christiansen},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.30.755678},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.30.755678v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Immediate cortical responses to transcranial magnetic stimulation of the human motor leg area
AU  - M. M. Beck
AU  - M. Nuyts
AU  - L. Sakalauskaite
AU  - J. Rothwell
AU  - H. R. Siebner
AU  - L. Christiansen
PY  - 2026
DA  - 2026/09/30
PB  - bioRxiv
DO  - 10.64898/2026.09.30.755678
UR  - https://www.biorxiv.org/content/10.64898/2026.09.30.755678v1
AB  - 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.
ER  -