Dataset Information

Axonal blockage with microscopic magnetic stimulation.

ABSTRACT: Numerous neurological dysfunctions are characterized by undesirable nerve activity. By providing reversible nerve blockage, electric stimulation with an implanted electrode holds promise in the treatment of these conditions. However, there are several limitations to its application, including poor bio-compatibility and decreased efficacy during chronic implantation. A magnetic coil of miniature size can mitigate some of these problems, by coating it with biocompatible material for chronic implantation. However, it is unknown if miniature coils could be effective in axonal blockage and, if so, what the underlying mechanisms are. Here we demonstrate that a submillimeter magnetic coil can reversibly block action potentials in the unmyelinated axons from the marine mollusk Aplysia californica. Using a multi-compartment model of the Aplysia axon, we demonstrate that the miniature coil causes a significant local depolarization in the axon, alters activation dynamics of the sodium channels, and prevents the traveling of the invading action potentials. With improved biocompatibility and capability of emitting high-frequency stimuli, micro coils provide an interesting alternative for electric blockage of axonal conductance in clinical settings.

SUBMITTER: Skach J

PROVIDER: S-EPMC7582966 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Axonal blockage with microscopic magnetic stimulation.

Skach Jordan J Conway Catherine C Barrett Lauryn L Ye Hui H

Scientific reports 20201022 1

Numerous neurological dysfunctions are characterized by undesirable nerve activity. By providing reversible nerve blockage, electric stimulation with an implanted electrode holds promise in the treatment of these conditions. However, there are several limitations to its application, including poor bio-compatibility and decreased efficacy during chronic implantation. A magnetic coil of miniature size can mitigate some of these problems, by coating it with biocompatible material for chronic implan ...[more]

PMID: 33093520

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Project description:Magnetic stimulation for neural activation is widely used in clinical and lab research. In comparison to electric stimulation using an implanted electrode, stimulation with a large magnetic coil is associated with poor spatial specificity and incapability to stimulate deep brain structures. Recent developments in micromagnetic stimulation (μMS) technology mitigates some of these shortcomings. The sub-millimeter coils can be covered with soft, biocompatible material, and chronically implanted. They can provide highly specific neural stimulation in the deep neural structure. Although the μMS technology is expected to provide a precise location of neural stimulation, the exact site of neural activation is difficult to determine. Furthermore, factors that could cause the shifting of the activation site during μMS have not been fully investigated. To estimate the location of axon activation in μMS, we first derived an analytical expression of the activating function, which predicts the location of membrane depolarization in an unmyelinated axon. Then, we developed a multi-compartment, Hodgkin-Huxley (H-H) type of NEURON model of an unmyelinated axon to test the impact of several important coil parameters on the location of axonal activation. The location of axonal activation was dependent on both the parameters of the stimulus and the biophysics properties of the targeted axon during μMS. The activating function analysis predicted that the location of membrane depolarization and activation could shift due to the reversal of the coil current and the change in the coil-axon distance. The NEURON modeling confirmed these predictions. Interestingly, the NEURON simulation further revealed that the intensity of stimulation played a significant role in the activation location. Moderate or strong coil currents activated the axon at different locations, mediated by two distinct ion channel mechanisms. This study reports several experimental factors that could cause a potential shift in the location of neural activation during μMS, which is essential for further development of this novel technology.

Project description:Medical imaging has played a major role in defining the general anatomical targets for deep brain stimulation (DBS) therapies. However, specifics on the underlying brain circuitry that is directly modulated by DBS electric fields remain relatively undefined. Detailed biophysical modeling of DBS provides an approach to quantify the theoretical responses to stimulation at the cellular level, and has established a key role for axonal activation in the therapeutic mechanisms of DBS. Estimates of DBS-induced axonal activation can then be coupled with advances in defining the structural connectome of the human brain to provide insight into the modulated brain circuitry and possible correlations with clinical outcomes. These pathway-activation models (PAMs) represent powerful tools for DBS research, but the theoretical predictions are highly dependent upon the underlying assumptions of the particular modeling strategy used to create the PAM. In general, three types of PAMs are used to estimate activation: 1) field-cable (FC) models, 2) driving force (DF) models, and 3) volume of tissue activated (VTA) models. FC models represent the "gold standard" for analysis but at the cost of extreme technical demands and computational resources. Consequently, DF and VTA PAMs, derived from simplified FC models, are typically used in clinical research studies, but the relative accuracy of these implementations is unknown. Therefore, we performed a head-to-head comparison of the different PAMs, specifically evaluating DBS of three different axonal pathways in the subthalamic region. The DF PAM was markedly more accurate than the VTA PAMs, but none of these simplified models were able to match the results of the patient-specific FC PAM across all pathways and combinations of stimulus parameters. These results highlight the limitations of using simplified predictors to estimate axonal stimulation and emphasize the need for novel algorithms that are both biophysically realistic and computationally simple.

Dataset Information

Axonal blockage with microscopic magnetic stimulation.

Publications

Axonal blockage with microscopic magnetic stimulation.

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