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 TMSinduced 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 current's 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.

Multimodal finger-printing of the human precentral cortex forming the motor hand knob

“…Therefore, we could use lower stimulus intensities which improved the focality of our mapping procedure by using a small-size dedicated coil. Since the second phase of a biphasic TMS pulse dominates the effect on the neural membranes (8,36), we secured that the second phase of the biphasic pulse induced a posterior-anterior current direction in the precentral gyrus. Future work needs to systematically address how the inter-individual differences in hotspot rostrality are influenced by the orientation of the TMS-induced currents in the precentral hand knob, for instance by using monophasic current configurations.…”

“…The primary site of TMS-induced axonal excitation is largely determined by the absolute magnitude of the TMS-induced electrical field (8). This also applies to the precentral gyrus hosting the motor hand representation.…”

“…This also applies to the precentral gyrus hosting the motor hand representation. The preferential site of direct TMS-induced excitation is the crown-and-lip region, because the electrical field strength is highest in this most superficial part of the precentral gyrus (8)(9)(10). Cytoarchitectonic mapping studies showed that the rostral border of the primary motor cortex is located at the surface of the precentral crown close to the midline, but disappears in the rostral bank of the central sulcus in more lateral parts of the hemisphere (11,12).…”

Site-specific effects of online rTMS during a working memory task in healthy older adults

“…As such, traditional amplitude calibration based on the motor threshold may lead to substantial variation in the desired E-field strength in the targeted brain region. This may lead to response variability, since the Efield strength is the key determinant of neural activation by TMS (Aberra, Wang. Grill, & Peterchev, 2018).…”

“…The likely explanation for the optimality of current perpendicular to the sulcal wall is that this current orientation induces the strongest E-field in the corresponding gyrus (Janssen, Oostendorp, & Stegeman, 2015). The likely reason for the sensitivity to current direction (current flowing into the gyrus) is the morphology and orientation of pyramidal neurons in the cortex (Aberra et al, 2018). Furthermore, we found no effect of cortical thickness across subjects on the observed TMS-related effects on performance, suggesting that E-field modeling is a good method to prevent this bias (Supplementary, Figure S5).…”