Simulation of transcranial magnetic stimulation in head model with morphologically-realistic cortical neurons

Abstract

Transcranial magnetic stimulation (TMS) enables non-invasive modulation of brain activity with both clinical and research applications, but fundamental questions remain about the neural types and elements it activates and how stimulation parameters affect the neural response. We integrated detailed neuronal models with TMS-induced electric fields in the human head to quantify the effects of TMS on cortical neurons. TMS activated with lowest intensity layer 5 pyramidal cells at their intracortical axonal terminations in the superficial gyral crown and lip regions. Layer 2/3 pyramidal cells and inhibitory basket cells may be activated too, whereas direct activation of layers 1 and 6 was unlikely. Neural activation was largely driven by the field magnitude, contrary to theories implicating the field component normal to the cortical surface. Varying the induced currents direction caused a waveform-dependent shift in the activation site and provided a mechanistic explanation for experimentally observed differences in thresholds and latencies of muscle responses. This biophysically-based simulation provides a novel method to elucidate mechanisms and inform parameter selection of TMS and other forms of cortical stimulation.