Biology subjects

Peterchev, A. V.

Publications and source records attributed to Peterchev, A. V..

42 records · Page 3Linked to original sources

bioRxiv2018

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

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.

bioengineering↗

bioRxiv2018

Conditions for numerically accurate TMS electric field simulation

BackgroundComputational simulations of the E-field induced by transcranial magnetic stimulation (TMS) are increasingly used to understand its mechanisms and to inform its administration. However, characterization of the accuracy of the simulation methods and the factors that affect it is lacking.\n\nObjectiveTo ensure the accuracy of TMS E-field simulations, we systematically quantify their numerical error and provide guidelines for their setup.\n\nMethodWe benchmark the accuracy of computational approaches that are commonly used for TMS E-field simulations, including the finite element method (FEM), boundary element method (BEM), finite difference method (FDM), and coil modeling methods.\n\nResultsTo achieve cortical E-field error levels below 2%, the commonly used FDM and 1st order FEM require meshes with an average edge length below 0.4 mm, whereas BEM and 2nd (or higher) order FEM require edge lengths below 1.5 mm, which is more practical. Coil models employing magnetic and current dipoles require at least 200 and 3,000 dipoles, respectively. For thick solid-conductor coils and frequencies above 3 kHz, winding eddy currents may have to be modeled.\n\nConclusionBEM, FDM, and FEM methods converge to the same solution. However, FDM and 1st order FEM converge slowly with increasing mesh resolution; therefore, the use of BEM or 2nd (or higher) order FEM is recommended. In some cases, coil eddy currents must be modeled. Both electric current dipole and magnetic dipole models of the coil current can be accurate with sufficiently fine discretization.\n\nFundingResearch reported in this publication was supported by the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Numbers RF1MH114268 and R01NS088674-S1. The content of current research is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.\n\nHIGHLIGHTSO_LIFDM and 1st order FEM with 1.5 mm average mesh edge length have numerical errors above 7%.\nC_LIO_LIBEM or 2nd order FEM are most efficient for achieving numerical errors < 2%.\nC_LIO_LICoil wire cross-section must be accounted to achieve E-field errors below < 2%.\nC_LIO_LICoil eddy currents can account for > 2% of E-field when very brief pulses are used.\nC_LI

bioengineering↗

bioRxiv2018

Statistical Model of Motor Evoked Potentials for Simulation of Transcranial Magnetic and Electric Stimulation

Motor evoked potentials (MEPs) are widely used for biomarkers and dose individualization in transcranial stimulation. The large variability of MEPs requires sophisticated methods of analysis to extract information fast and correctly. However, models of MEPs that represent their characteristic features are lacking. This work presents a statistical model that can simulate long sequences of individualized MEP amplitude data with properties matching experimental observations. The MEP model includes three sources of trial-to-trial variability to mimic excitability fluctuations, variability in the neural and muscular pathways, and physiological and measurement noise. It also generates virtual human subject data from statistics of population variability. All parameters are extracted as statistical distributions from experimental data from the literature. The model exhibits previously described features, such as stimulusintensity-dependent MEP amplitude distributions, including bimodal ones. The model can generate long sequences of test data for individual subjects with specified parameters or for subjects from a virtual population. The presented MEP model is the most detailed to date and can be used for the development and implementation of dosing and biomarker estimation algorithms for transcranial stimulation.

physiology↗

bioRxiv2018

Biophysically Realistic Neuron Models for Simulation of Cortical Stimulation

1.ObjectiveWe implemented computational models of human and rat cortical neurons for simulating the neural response to cortical stimulation with electromagnetic fields.\n\nApproachWe adapted model neurons from the library of Blue Brain models to reflect biophysical and geometric properties of both adult rat and human cortical neurons and coupled the model neurons to exogenous electric fields (E-fields). The models included 3D reconstructed axonal and dendritic arbors, experimentally-validated electrophysiological behaviors, and multiple, morphological variants within cell types. Using these models, we characterized the single-cell responses to intracortical microstimulation (ICMS) and uniform E-field with dc as well as pulsed currents.\n\nMain resultsThe strength-duration and current-distance characteristics of the model neurons to ICMS agreed with published experimental results, as did the subthreshold polarization of cell bodies and axon terminals by uniform dc E-fields. For all forms of stimulation, the lowest threshold elements were terminals of the axon collaterals, and the dependence of threshold and polarization on spatial and temporal stimulation parameters was strongly affected by morphological features of the axonal arbor, including myelination, diameter, and branching.\n\nSignificanceThese results provide key insights into the mechanisms of cortical stimulation. The presented models can be used to study various cortical stimulation modalities while incorporating detailed spatial and temporal features of the applied E-field.

bioengineering↗

bioRxiv2018

Design of Transcranial Magnetic Stimulation Coils with Optimal Trade-off between Depth, Focality, and Energy

BackgroundTranscranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique used for research and clinical applications. Existent TMS coils are limited in their precision of spatial targeting (focality), especially for deeper targets.\n\nObjectiveThis paper presents a methodology for designing TMS coils to achieve optimal trade-off between the depth and focality of the induced electric field (E-field), as well as the energy required by the coil.\n\nMethodsA multi-objective optimization technique is used for computationally designing TMS coils that achieve optimal trade-offs between stimulation focality, depth, and energy (fdTMS coils). The fdTMS coil winding(s) maximize focality (minimize stimulated volume) while reaching a target at a specified depth and not exceeding predefined peak E-field strength and required coil energy. Spherical and MRI-derived head models are used to compute the fundamental depth-focality trade-off as well as focality-energy trade-offs for specific target depths.\n\nResultsAcross stimulation target depths of 1.0-3.4 cm from the brain surface, the stimulated volume can be theoretically decreased by 42%-55% compared to existing TMS coil designs. The stimulated volume of a figure-8 coil can be decreased by 36%, 44%, or 46%, for matched, doubled, or quadrupled energy. For matched focality and energy, the depth of a figure-8 coil can be increased by 22%.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=153 SRC=\"FIGDIR/small/300616_fig8.gif\" ALT=\"Figure 8\">\nView larger version (14K):\norg.highwire.dtl.DTLVardef@af0b5org.highwire.dtl.DTLVardef@4118d8org.highwire.dtl.DTLVardef@1c61f80org.highwire.dtl.DTLVardef@3e23fa_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 8.C_FLOATNO Energy, W, vs. spread, S1/2, curves for hand knob stimulation for a conventional figure-8 coil and optimized fdTMS coil on a 32 x 32 cm square plane.\n\nC_FIG ConclusionComputational design of TMS coils could enable more selective targeting of the induced E-field. The presented results appear to be the first significant advancement in the depth-focality trade-off of TMS coils since the introduction of the figure-8 coil three decades ago, and likely represent the fundamental physical limit.\n\nDECLARATION OF INTERESTThe fdTMS technology described in this paper is subject to a provisional patent application by Duke University with the authors as inventors. Additionally: L.J.G. is inventor on a patent pertaining to the design of focal multicoil TMS systems. S.M.G. is inventor on patents and patent applications; he has received royalties from Rogue Research, TU Muenchen, and Porsche; furthermore, he has been provided with research support and patent fee reimbursement from Magstim Co. A.V.P. is inventor on patents and patent applications, and has received research and travel support as well as patent royalties from Rogue Research; research and travel support, consulting fees, as well as equipment loan from Tal Medical / Neurex; patent application and research support from Magstim; and equipment loans from MagVenture, all related to technology for transcranial magnetic stimulation.

bioengineering↗

bioRxiv2018

Coupling magnetically induced electric fields to neurons: longitudinal and transverse activation

We present a theory and computational models to couple the electric field induced by magnetic stimulation to neuronal membranes. The response of neuronal membranes to induced electric fields is examined under different time scales, and the characteristics of the primary and secondary electric fields from electromagnetic induction and charge accumulation on conductivity boundaries, respectively, are analyzed. Based on the field characteristics and decoupling of the longitudinal and transverse field components along the neural cable, quasi-potentials are a simple and accurate approximation for coupling of magnetically induced electric fields to neurons and a modified cable equation provides theoretical consistency for magnetic stimulation. The conventional and modified cable equations are used to simulate magnetic stimulation of long peripheral nerves by circular and figure-8 coils. Activation thresholds are obtained over a range of lateral and vertical coil positions for two nonlinear membrane models representing unmyelinated and myelinated axons and also for undulating myelinated axons. For unmyelinated straight axons, the thresholds obtained with the modified cable equation are significantly lower due to transverse polarization, and the spatial distributions of thresholds as a function of coil position differ significantly from predictions by the activating function. For myelinated axons, the transverse field contributes negligibly to activation thresholds, whereas axonal undulation can increase or decrease thresholds depending on coil position. The analysis provides a rigorous theoretical foundation and implementation methods for the use of the cable equation to model neuronal response to magnetically induced electric fields. Experimentally observed stimulation with the electric fields perpendicular to the nerve trunk cannot be explained by transverse polarization alone and is likely due to nerve fiber undulation and other geometrical inhomogeneities.

bioengineering↗