Abstract
There are recent efforts developing multi-scale models for NIBS dose control. While the induced electric field is the key factor to determine dosing and target engagement, it is only a first step to model the physiological response. To advance these efforts we have developed a new multi-scale pipeline (NeMo-TMS) for modeling TMS effects across spatial scales. On the macro-scale, we simulate TMS electric fields using SimNIBS. Afterwards, electric fields are coupled with morphologically realistic neuronal models in the NEURON environment. These neuron-scale simulations allow the investigation of membrane voltage, action potential initiation and propagation, field intensity, and orientation necessary for modulating neuron response. Finally, we incorporate the membrane voltage data to simulate the calcium concentration induced by voltage-gated calcium-channels at the subcellular scale by solving the calcium dynamics equations. This allows us to model effects of rTMS protocols on somatic calcium accumulation, important for neural plasticity. The experimental results of model validation based on invasive recordings in non-human primates will be presented. We stimulate different brain regions with TMS at different intensities and a sham protocol. Our key findings are a dose-dependent effect of TMS evoked potentials (TEP) at 50 ms in frontal contacts in FEF and TEM electrodes and coil location-dependent effect of center of activation. These results support the premise that TMS induces direct neural responses in a dose-dependent and targeted manner. There are still existing challenges and limitations of computational models. Computational models have greatly improved our understanding of NIBS biophysics and can inform stimulation design and dosing. However, modeling technologies are still actively developed, and current models have several limitations. For example, tissue conductivities are often based on ex-vivo measurements and population averages. Individual differences in tissue conductivities are substantial and can result in significant uncertainty in the electric field estimates per individual.