Determining which mechanisms lead to activation in the motor cortex: A modeling study of transcranial magnetic stimulation using realistic stimulus waveforms and sulcal geometry

Abstract

Objective-To determine which mechanisms lead to activation of neurons in the motor cortex during transcranial magnetic stimulation (TMS) with different current directions and pulse waveforms.Methods-The total electric field induced in a simplified model of a cortical sulcus by a figureeight coil was calculated using the finite element method (FEM). This electric field was then used as the input to determine the response of compartmental models of several types of neurons.Results-The modeled neurons were stimulated at different sites: fiber bends for pyramidal tract neurons, axonal terminations for cortical interneurons and axon collaterals, and a combination of both for pyramidal association fibers. All neurons were more easily stimulated by a PA directed electric field, except association fibers. Additionally, the second phase of a biphasic pulse was found to be more efficient than the first phase of either monophasic or biphasic pulses. Conclusion-The stimulation threshold for different types of neurons depends on the pulse waveform and current direction. The reported results might account for the range of responses obtained in TMS of the motor cortex when using different stimulation parameters.Significance-Modeling studies combining electric field calculations and neuronal models may lead to a deeper understanding of the effect of the TMS-induced electric field on cortical tissue, and may be used to evaluate improvements in TMS coil and waveform design.

Evoked potentials in large-scale cortical networks elicited by TMS of the visual cortex

“…Although detailed finite element (FEM) models have been used to estimate the induced electrical field at the stimulation site (Salvador et al 2010;Silva et al 2007), such models still do not account for the synaptic interactions of the stimulated neurons within the functional network engaged by the cascade of neural firing following a TMS pulse. The functional connectivity of the stimulation site constrains the excitation to the nodes that are dynamically linked to the stimulation region (Amassian et al 1998;Ruohonen and Ilmoniemi 1999).…”

Cytoarchitectonic and Dynamic Origins of Giant Positive Local Field Potentials in the Dentate Gyrus

“…Accordingly, the size and geometry of the blocks of current represent the physical extension of the synchronously activated GCs, i.e., the portion of the GC population that elicits postsynaptic currents upon coherent activation of a group of axons from homologous afferent units (Benito et al, 2013). The FEM approach is widely used in magnetoencephalography and scalp electroencephalogram (EEG; Chen and Mogul, 2009;Salvador et al, 2011;Thielscher et al, 2011), although to the best of our knowledge it has not previously been used in the study of LFPs where the modeling approaches included realistic connectivity and/or membrane electrogenesis (Pauluis et al, 1999;Varona et al, 2000;Ló pez-Aguado et al, 2002;Lindén et al, 2011;Makarova et al, 2011;Ho et al, 2012).…”

“…The amplitude and polarity of LFPs is critically determined by spatial factors, such as the distribution of coactivated synapses, neuronal morphology, and the architectonic configuration of the cell population (Kajikawa and Schroeder, 2011;Makarova et al, 2011;Ho et al, 2012). Although the arrangement of cells in layers and curved structures is recognized as key feature on a theoretical basis (Woodbury, 1960;Gloor, 1985;Nunez and Srinivasan, 2006), the study requires quantitative explicit modeling and in vivo analysis.…”

Selective stimulation of the subthalamic nucleus

“…This is in agreement with earlier modelling studies Wongsarnpigoon and Grill 2012). Like Salvador et al (Salvador et al 2011), we found that during cathodal stimulation, the action potential was generated at the axon collateral in the vertical pyramidal axon (Fig. 3, blue).…”

“…The inhibitory axonal population was represented by Basket cell axons, which were modelled as long axons running parallel to the pial surface at depths of 1950 μm and 850 μm from the pial surface, being halfway the V (2) a diagonal axon running through the lip (purple); and (3) a horizontal axon running through the sulcus bank (green) ). They were also placed in z-direction from -15 to +15 mm, using 31 xy-planes spaced 1 mm apart, obtaining a population of 93 PT type axons in layer V, 93 IT type axons in both layer III and V. The pyramidal axons were represented by a main axon and an axon collateral (Nieuwenhuys 1994;Salvador et al 2011) (Fig. 3).…”