We describe a routine to precisely localize cortical muscle representations within the primary motor cortex with transcranial magnetic stimulation (TMS) based on the functional relation between induced electric fields at the cortical level and peripheral muscle activation (motor-evoked potentials; MEPs). Besides providing insights into structure–function relationships, this routine lays the foundation for TMS dosing metrics based on subject-specific cortical electric field thresholds. MEPs for different coil positions and orientations are combined with electric field modeling, exploiting the causal nature of neuronal activation to pinpoint the cortical origin of the MEPs. This involves constructing an individual head model using magnetic resonance imaging, recording MEPs via electromyography during TMS and computing the induced electric fields with numerical modeling. The cortical muscle representations are determined by relating the TMS-induced electric fields to the MEP amplitudes. Subsequently, the coil position to optimally stimulate the origin of the identified cortical MEP can be determined by numerical modeling. The protocol requires 2 h of manual preparation, 10 h for the automated head model construction, one TMS session lasting 2 h, 12 h of computational postprocessing and an optional second TMS session lasting 30 min. A basic level of computer science expertise and standard TMS neuronavigation equipment suffices to perform the protocol.
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We provide a full example dataset51 for one subject to follow along all steps in this protocol. These data are real experimental data and have been part of a previous study2. The dataset includes raw MRI data to construct a head model, EMG and TMS data, and also includes intermediate steps of the analysis pipeline and the final results. Figures 2, 10, 12 and 14–16 were generated using the example dataset51.
All code51 needed to complete the localization procedure is presented at https://gitlab.gwdg.de/tms-localization/papers/tmsloc_proto.
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This work was partially supported by the German Science Foundation (DFG) (grant number WE 59851/2 to K.W.; HA 6314/9-1 to G.H.; KN 588/10-1 to T.K.; HA 2899/31-1 to J.H.), Lundbeckfonden (grant no. R244-2017-196 and R313-2019-622) and the NVIDIA Corporation (donation of two Titan Xp graphics cards to G.H. and K.W.).
The authors declare no competing interests.
Peer review information
Nature Protocols thanks Petro Julkunen and Nicholas L. Balderston for their contribution to the peer review of this work.
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Key references using this protocol
Weise, K. et al. NeuroImage 209, 116486 (2020): https://doi.org/10.1016/j.neuroimage.2019.116486
Numssen, O. et al. NeuroImage 245, 118654 (2021): https://doi.org/10.1016/j.neuroimage.2021.118654
Key data used in this protocol
Numssen, O. et al. OSF (2022): https://doi.org/10.17605/OSF.IO/MYRQN
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Weise, K., Numssen, O., Kalloch, B. et al. Precise motor mapping with transcranial magnetic stimulation. Nat Protoc 18, 293–318 (2023). https://doi.org/10.1038/s41596-022-00776-6
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