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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