Dataset Information

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

ABSTRACT:

Background

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 TMS activates and how stimulation parameters affect the neural response.

Objective

To develop a multi-scale computational model to quantify the effect of TMS parameters on the direct response of individual neurons.

Methods

We integrated morphologically-realistic neuronal models with TMS-induced electric fields computed in a finite element model of a human head to quantify the cortical response to TMS with several combinations of pulse waveforms and current directions.

Results

TMS activated with lowest intensity intracortical axonal terminations in the superficial gyral crown and lip regions. Layer 5 pyramidal cells had the lowest thresholds, but layer 2/3 pyramidal cells and inhibitory basket cells were also activated at most intensities. Direct activation of layers 1 and 6 was unlikely. Neural activation was largely driven by the field magnitude, rather than the field component normal to the cortical surface. Varying the induced current direction caused a waveform-dependent shift in the activation site and provided a potential mechanism for experimentally observed differences in thresholds and latencies of muscle responses.

Conclusions

This biophysically-based simulation provides a novel method to elucidate mechanisms and inform parameter selection of TMS and other cortical stimulation modalities. It also serves as a foundation for more detailed network models of the response to TMS, which may include endogenous activity, synaptic connectivity, inputs from intrinsic and extrinsic axonal projections, and corticofugal axons in white matter.

SUBMITTER: Aberra AS

PROVIDER: S-EPMC6889021 | biostudies-literature | 2020 Jan - Feb

REPOSITORIES: biostudies-literature

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Publications

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

Aberra Aman S AS Wang Boshuo B Grill Warren M WM Peterchev Angel V AV

Brain stimulation 20191007 1

<h4>Background</h4>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 TMS activates and how stimulation parameters affect the neural response.<h4>Objective</h4>To develop a multi-scale computational model to quantify the effect of TMS parameters on the direct response of individual neurons.<h4>Methods</h4>We integrated morphologically-realistic ...[more]

PMID: 31611014

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Project description:BackgroundTranscranial direct current stimulation (tDCS) is a non-invasive brain stimulation modality that can alter cortical excitability. However, it remains unclear how the subcellular elements of different neuron types are polarized by specific electric field (E-field) distributions.ObjectiveTo quantify neuronal polarization generated by tDCS in a multi-scale computational model.MethodsWe embedded layer-specific, morphologically-realistic cortical neuron models in a finite element model of the E-field in a human head and simulated steady-state polarization generated by conventional primary-motor-cortex-supraorbital (M1-SO) and 4 × 1 high-definition (HD) tDCS. We quantified somatic, axonal, and dendritic polarization of excitatory pyramidal cells in layers 2/3, 5, and 6, as well as inhibitory interneurons in layers 1 and 4 of the hand knob.ResultsAxonal and dendritic terminals were polarized more than the soma in all neurons, with peak axonal and dendritic polarization of 0.92 mV and 0.21 mV, respectively, compared to peak somatic polarization of 0.07 mV for 1.8 mA M1-SO stimulation. Both montages generated regions of depolarization and hyperpolarization beneath the M1 anode; M1-SO produced slightly stronger, more diffuse polarization peaking in the central sulcus, while 4 × 1 HD produced higher peak polarization in the gyral crown. The E-field component normal to the cortical surface correlated strongly with pyramidal neuron somatic polarization (R2>0.9), but exhibited weaker correlations with peak pyramidal axonal and dendritic polarization (R2:0.5-0.9) and peak polarization in all subcellular regions of interneurons (R2:0.3-0.6). Simulating polarization by uniform local E-field extracted at the soma approximated the spatial distribution of tDCS polarization but produced large errors in some regions (median absolute percent error: 7.9 %).ConclusionsPolarization of pre- and postsynaptic compartments of excitatory and inhibitory cortical neurons may play a significant role in tDCS neuromodulation. These effects cannot be predicted from the E-field distribution alone but rather require calculation of the neuronal response.

Project description:Objective.Temporal interference stimulation (TIS) was proposed as a non-invasive, focal, and steerable deep brain stimulation method. However, the mechanisms underlying experimentally-observed suprathreshold TIS effects are unknown, and prior simulation studies had limitations in the representations of the TIS electric field (E-field) and cerebral neurons. We examined the E-field and neural response characteristics for TIS and related transcranial alternating current stimulation modalities.Approach.Using the uniform-field approximation, we simulated a range of stimulation parameters in biophysically realistic model cortical neurons, including different orientations, frequencies, amplitude ratios, amplitude modulation, and phase difference of the E-fields, and obtained thresholds for both activation and conduction block.Main results. For two E-fields with similar amplitudes (representative of E-field distributions at the target region), TIS generated an amplitude-modulated (AM) total E-field. Due to the phase difference of the individual E-fields, the total TIS E-field vector also exhibited rotation where the orientations of the two E-fields were not aligned (generally also at the target region). TIS activation thresholds (75-230 V m-1) were similar to those of high-frequency stimulation with or without modulation and/or rotation. For E-field dominated by the high-frequency carrier and with minimal amplitude modulation and/or rotation (typically outside the target region), TIS was less effective at activation and more effective at block. Unlike AM high-frequency stimulation, TIS generated conduction block with some orientations and amplitude ratios of individual E-fields at very high amplitudes of the total E-field (>1700 V m-1).Significance. The complex 3D properties of the TIS E-fields should be accounted for in computational and experimental studies. The mechanisms of suprathreshold cortical TIS appear to involve neural activity block and periodic activation or onset response, consistent with computational studies of peripheral axons. These phenomena occur at E-field strengths too high to be delivered tolerably through scalp electrodes and may inhibit endogenous activity in off-target regions, suggesting limited significance of suprathreshold TIS.

Dataset Information

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

Background

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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