Introduction Transcranial magnetic stimulation (TMS) of the human primary motor cortex (M1) is well studied, aided by abundant possible experimental readouts, such as EEG and motor evoked potentials (MEP). One key readout are DI-waves, reflecting the TMS-evoked output of M1 and characteristically depend on TMS parameters (e.g., coil orientation and pulse strength). Previous modeling studies approximate TMS inputs in a more abstract way as currents or synaptic inputs, thereby missing the biophysical coupling between TMS induced electric fields and the neural states. This study uses cable simulations of realistic neuron morphologies to couple electric fields (and thereby stimulation parameters) to the firing patterns of cortical output neurons [1].
Methods The coupling model leverages a number of realistic neuronal morphologies for simulating the elicitation of action potentials in upstream cells projecting onto the cortical output neurons, the spreading of the activation across the axonal arbors of these cells, the synaptic coupling onto the output neurons, and the dendritic dynamics in these cells. Averaging over cell morphologies and orientations leads to a statistical kernel representation linking the field to the average input kernel entering the somata of the output neurons. An example M1 cortical circuit is studied, in which TMS stimulates layer 2/3 excitatory and inhibitory neurons that project synapses onto layer 5 corticospinal neurons.
Results Results indicate that TMS induces unique directionally sensitive distributions of synaptic outputs in time and space for each cell type. Directional and dosage sensitivity carries forward to the dendritic current flowing into layer 5 cells, which can then be translated into cortical output firing patterns.
Discussion The proposed coupling model provides a novel architecture to translate electric fields from TMS into activation functions that alter neural states and may serve as inputs to cortical circuit modeling. The study of other brain regions is achievable through an alternate choice of cell morphologies, cell locations, and circuit design.
References
1. Miller, A., Knösche, T.R., Weise, K. (2026). A coupling model of transcranial magnetic stimulation induced electric fields to neural state variables. Brain Stimulation, in press (preprint at https://www.biorxiv.org/content/10.1101/2025.08.11.669601v1)
Acknowledgement The authors thank Torge Worbs for consultation and support in developing the model interface to 610 NEURON. This study has received support from BMBF grant 01GQ2201.
