P200 Modeling the response of cortical cell populations to transcranial magnetic stimulation
Aaron Miller1, Konstantin Weise1,2,Thomas R. Knösche*1,3
1Max Planck Institute for Human Cogntitive and Brain Sciences, Leipzig, Germany
2Leipzig University of Applied Sciences, Germany
3Technical University Ilmenau, Germany
*email: knoesche@cbs.mpg.de Introduction
The response of cortical neurons to TMS depends on the locally induced electric field magnitude and direction as well as on the physiological, biophysical, and microstructural properties of the involved cells. Here, we provide a modeling framework to integrate standard neural population modeling with numerically estimated TMS induced electric fields, mediated by detailed information on cell morphology and physiology. We exemplify this framework for the stimulation of primary motor cortex (M1), giving rise to observable electromyographic recordings in muscles (motor evoked potentials – MEP) as well as fast activity volleys in the EEG (DI-waves).
Methods The model comprises pairs of pre/postsynaptic neural populations and their generation of short-latency (<10ms) responses upon TMS. We focus on the generation of I-waves by activation of neurons that project to layer 5 (L5) corticospinal neurons. We use realistic compartment models to simulate spatiotemporal spiking dynamics on the axonal arbors of presynaptic neurons. This output is coupled into L5 cells according the morphologies of presynaptic axonal and postsynaptic dendritic trees. The resulting current entering L5 somata defines an average current input to a neural mass model. We explore their sensitivity towards model parameters using a generalized polynomial chaos (gPC) approach.
Results Fig. 1A-C show the resulting modeling pipeline. The output activity of L5 neurons due to stimulation of upstream L2/3 neurons is presented in Fig. 1D. We observe a strong directional dependency at low and medium intensity, decreasing at higher intensities, which agrees with experimental and modeling results (Souza et al., 2022; Weise et al., 2023). A gPC surrogate of the activity function using 4000 model evaluations with random parameter distributions resulted in a normalized root mean square deviation of 1.9% tested against 1000 independent verification runs. The average Sobol indices revealed the most influencing parameters and combinations thereof, i.e. E/I balance (42%), stimulation intensity (13%), and a combination of both (14%).
Discussion The model provides the basis for modeling TMS evoked activity using parsimonious NMM with high biological detail. Previous coupling models were based on coarse approximations and ignored the complex mechanisms of how TMS activates neuronal populations. The model pipeline can also be adapted to other brain stimulation methods such as tDCS. The calculated surrogate models will be provided for download in order to allow efficient calculation of the input currents to L5 PC.
Figure 1. A: Parameters of the TMS induced electric field; B and C: Illustration of the model pipeline - induced e-field acts on terminals of presynaptic axons. Spreading of activity in axonal arbors is captured by the axonal delay kernel. The postsynaptic synapto-dendritic delay kernel accounts for extra position-dependent delay and yields current entering soma; D: Resulting input current to L5 PC over tim Acknowledgements The publication was supported by BMBF grant 01GQ2201 (KW, TRK). References K. Weise, T. Worbs, B. Kalloch, V.H. Souza, A.T. Jaquier, W. Van Geit, A. Thielscher, T.R. Knösche: Directional Sensitivity of Cortical Neurons Towards TMS Induced Electric Fields. Imaging Neuroscience 1: 1–22 (2023)
V.H. Souza, J.O. Nieminen, S. Tugin, L.M. Koponen, O. Baffa, R.J. Ilmoniemi: TMS with fast and accurate electronic control: Measuring the orientation sensitivity of corticomotor pathways. Brain Stimulation 15(2), 306–315 (2022)
