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Front. Comput. Neurosci. | doi: 10.3389/fncom.2019.00017

Location Specificity of Transcranial Electrical Stimulation on Neuronal Electrodynamics: A Mathematical Model of Ion Channel Gating Dynamics and Ionic Flux Due to Neurostimulation

  • 1Department of Mathematics, Roger Williams University, United States

Transcranial Electrical Stimulation (TES) continues to demonstrate success as a medical intervention for individuals with neurodegenerative diseases. Despite promising results from these neuromodulation modalities, the cellular level mechanisms by which this neurotherapy operates are not fully comprehended. In particular, the effects of TES on ion channel gating and ion transport are not known. Using the Poisson-Nernst-Planck model of electrodiffusion, coupled with a Hodgkin-Huxley based model of cellular ion transport, we present a model of TES that, for the first time, integrates electric potential energy, individualized ion species, voltage-gated ion channels, and transmembrane ionic flux during TES administration. Computational simulations are executed on a biologically-inspired domain with medically-based TES treatment parameters and quantify neuron-level electrical processes resulting from this form of neurostimulation. Results confirm prior findings that show that TES polarizes the cell membrane, however, these are extended as simulations in this paper show that polarization occurs in a location specific manner, where the type and degree of polarization depends on the position on the membrane within a node of Ranvier. In addition, results demonstrate that TES causes ion channel gating variables to change in a location specific fashion and, as a result, transmembrane current from distinct ion species depends on both time and membrane location. Another simulation finding is that intracellular calcium concentrations increase significantly due to a TES-induced calcium influx. As cytosolic calcium is critical in intracellular signaling pathways that govern proper neurotransmitter secretion as well as support cell viability, this alteration in calcium homeostasis suggests a possible mechanism by which TES operates at the neuronal level to achieve neurotherapeutic success.

Keywords: Location Specificity of Neuronal Electrodynamics, Neurostimulation Induced Calcium Flux, mathematical model, Transcranial electrical stimulation, Finite element method simulation

Received: 07 Jul 2018; Accepted: 11 Mar 2019.

Edited by:

Yu-Guo Yu, Fudan University, China

Reviewed by:

Xiaojuan Sun, Beijing University of Posts and Telecommunications, China
Jacqueline Dresch, Clark University, United States  

Copyright: © 2019 Lindberg and Dougherty. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Edward T. Dougherty, Roger Williams University, Department of Mathematics, Bristol, United States, edougherty@rwu.edu