Directional sensitivity of cortical neurons towards TMS-induced electric fields

We derived computationally efficient average response models of different types of cortical neurons, which are subject to external electric fields from Transcranial Magnetic Stimulation. We used 24 reconstructions of pyramidal cells (PC) from layer 2/3, 245 small, nested, and large basket cells from layer 4, and 30 PC from layer 5 with different morphologies for deriving average models. With these models, it is possible to efficiently estimate the stimulation thresholds depending on the underlying electric field distribution in the brain, without having to implement and compute complex neuron compartment models. The stimulation thresholds were determined by exposing the neurons to TMS-induced electric fields with different angles, intensities, pulse waveforms, and field decays along the somato-dendritic axis. The derived average response models were verified by reference simulations using a high-resolution realistic head model containing several million neurons. The relative errors of the estimated thresholds between the average model and the reference model ranged between -3% and 3.7% in 98% of the cases, while the computation time was only a fraction of a second compared to several weeks. Finally, we compared the model behavior to TMS experiments and observed high correspondence to the orientation sensitivity of motor evoked potentials. The derived models were compared to the classical cortical column cosine model and to simplified ball-and-stick neurons. It was shown that both models oversimplify the complex interplay between the electric field and the neurons and do not adequately represent the directional sensitivity of the different cell types. The derived models are simple to apply and only require the TMS-induced electric field in the brain as input variable. The models and code are available to the general public in open-source repositories for integration into TMS studies to estimate the expected stimulation thresholds for an improved dosing and treatment planning in the future.