Sources of the N15 TMS-evoked potential following motor cortex stimulation localize rostrals to TMS-induced electric fields and depend on dose.

Overview

1. Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark
2. REVAL - Rehabilitation Research Center, Faculty of Rehabilitation Sciences, University of Hasselt, Diepenbeek, Belgium
3. Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany
4. Department of Human Sciences, Institute of Psychology, University of the Bundeswehr Munich, Neubiberg, Germany
5. Movement Control and Neuroplasticity Research Group - Department of Movement Sciences, Group Biomedical Sciences, KU Leuven, Leuven, Belgium
6. Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark
7. Institute for Clinical Medicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark
8. Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark

Abstract

Transcranial magnetic stimulation (TMS) elicits characteristic cortical responses known as TMS-evoked potentials (TEPs) measured via electroencephalography (EEG). An early negative peak can be consistently evoked over the motor cortex at around 15 ms (N15). It remains elusive whether N15 overlaps with the cortical regions receiving the highest TMS-induced electric field (E-field). We characterized the source activity of the N15 component relative to the TMS-induced E-field in 16 healthy adults who underwent TMS-EEG over the left primary motor hand area at six stimulus intensities (-8% to +12% maximum stimulator output relative to resting motor threshold) during rest and tonic contraction. Individualized head models, based on T1 and T2 MRI scans, were used for E-field simulations and source localization with LCMV, dSPM, and eLORETA as inverse solvers. Linear mixed-effects models and spatial clustering were used to assess dose- and state-dependent effects. The N15 source field was consistently located rostral to the TMS-induced electric field, with the spatial disparity decreasing as the stimulation dose increased. N15 source activity primarily clustered in the left premotor and primary motor cortex, while the TMS E-field peaked in the crowns of the pre- and postcentral gyri. All three inverse solvers yielded similar results, demonstrating consistent dose- and state-dependent effects on the N15 and suggesting that solver choice had minimal impact. These findings demonstrate a spatial mismatch between early TMS-evoked potentials following motor cortex stimulation and the cortical regions exposed to peak electric fields. Combined with prior literature, our findings provide evidence that the rostral N15 source activity reflects transsynaptic propagation via direct cortico-cortical or indirect cortico-subcortico-cortical pathways.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data and Code Availability

The data underlying this article are not publicly available due to ethical and regulatory constraints. Access may be granted to qualified researchers upon submission of a motivated request, subject to (i) the establishment of a formal data-sharing agreement, (ii) approval from the requesting researcher’s local ethics committee, and (iii) submission and approval of a detailed project outline describing the planned analyses and intended use of the data. Fulfilment of these conditions is required prior to any data sharing.

The analyses code are available from the corresponding author upon reasonable and justified request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 3, 28 September 2026

• Funding: added Innovationsfonden: 9068-00025B; Fonds Wetenschappelijk Onderzoek: G1129923N, V426023N; Lundbeckfonden: R336‐2020‐1035, R313–2019–622

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 7 authors, 8 keywords, 11 MeSH terms, 70 references.

Cite

This paper

Van Hoornweder, S., Beck, M. M., Nielsen, J. D., Tomasevic, L., Meesen, R. L., Siebner, H. R., & Thielscher, A. (2026). Sources of the N15 TMS-evoked potential following motor cortex stimulation localize rostrals to TMS-induced electric fields and depend on dose. Imaging neuroscience (Cambridge, Mass.), 4, IMAG.a.1356. https://doi.org/10.1162/imag.a.1356

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