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      Mechanisms of Magnetic Stimulation of Central Nervous System Neurons

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Transcranial magnetic stimulation (TMS) is a stimulation method in which a magnetic coil generates a magnetic field in an area of interest in the brain. This magnetic field induces an electric field that modulates neuronal activity. The spatial distribution of the induced electric field is determined by the geometry and location of the coil relative to the brain. Although TMS has been used for several decades, the biophysical basis underlying the stimulation of neurons in the central nervous system (CNS) is still unknown. To address this problem we developed a numerical scheme enabling us to combine realistic magnetic stimulation (MS) with compartmental modeling of neurons with arbitrary morphology. The induced electric field for each location in space was combined with standard compartmental modeling software to calculate the membrane current generated by the electromagnetic field for each segment of the neuron. In agreement with previous studies, the simulations suggested that peripheral axons were excited by the spatial gradients of the induced electric field. In both peripheral and central neurons, MS amplitude required for action potential generation was inversely proportional to the square of the diameter of the stimulated compartment. Due to the importance of the fiber's diameter, magnetic stimulation of CNS neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. Passive dendrites affect this process primarily as current sinks, not sources. The simulations predict that neurons with low current threshold are more susceptible to magnetic stimulation. Moreover, they suggest that MS does not directly trigger dendritic regenerative mechanisms. These insights into the mechanism of MS may be relevant for the design of multi-intensity TMS protocols, may facilitate the construction of magnetic stimulators, and may aid the interpretation of results of TMS of the CNS.

          Author Summary

          Transcranial magnetic stimulation (TMS) is a widely applied tool for probing cognitive function in humans and is one of the best tools for clinical treatments and interfering with cognitive tasks. Surprisingly, while TMS has been commercially available for decades, the cellular mechanisms underlying magnetic stimulation remain unclear. Here we investigate these mechanisms using compartmental modeling. We generated a numerical scheme allowing simulation of the physiological response to magnetic stimulation of neurons with arbitrary morphologies and active properties. Computational experiments using this scheme suggested that TMS affects neurons in the central nervous system (CNS) primarily by somatic stimulation. Since magnetic stimulation appears to cause somatic depolarization, its effects are highly correlated with the neuron's current threshold. Our simulations therefore predict that subpopulations of CNS neurons with different firing thresholds will respond differently to magnetic stimulation. For example, low-intensity TMS may be used to stimulate low-threshold cortical inhibitory interneurons. At higher intensities we predict that both inhibitory and excitatory neurons are activated. These predictions may be tested at the cellular level and may impact cognitive experiments in humans. Furthermore, our simulations may be used to design TMS coils, devices and protocols.

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          Interneurons of the neocortical inhibitory system.

          Mammals adapt to a rapidly changing world because of the sophisticated cognitive functions that are supported by the neocortex. The neocortex, which forms almost 80% of the human brain, seems to have arisen from repeated duplication of a stereotypical microcircuit template with subtle specializations for different brain regions and species. The quest to unravel the blueprint of this template started more than a century ago and has revealed an immensely intricate design. The largest obstacle is the daunting variety of inhibitory interneurons that are found in the circuit. This review focuses on the organizing principles that govern the diversity of inhibitory interneurons and their circuits.
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            Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex.

            Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.
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              Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Comput Biol
                plos
                ploscomp
                PLoS Computational Biology
                Public Library of Science (San Francisco, USA )
                1553-734X
                1553-7358
                March 2011
                March 2011
                24 March 2011
                : 7
                : 3
                : e1002022
                Affiliations
                [1 ]The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel
                [2 ]Department of Physics, Bar-Ilan University, Ramat-Gan, Israel
                [3 ]Department of Psychology, Bar-Ilan University, Ramat-Gan, Israel
                [4 ]The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel
                Université Paris Descartes, Centre National de la Recherche Scientifique, France
                Author notes

                Conceived and designed the experiments: TP YY IBG SW AF AK. Performed the experiments: TP AK. Analyzed the data: TP AK. Contributed reagents/materials/analysis tools: TP IBG AK. Wrote the paper: TP SW AF ML IBG YY AK. Attempted to reduce entropy: AK.

                Article
                PCOMPBIOL-D-10-00312
                10.1371/journal.pcbi.1002022
                3063755
                21455288
                d15244d0-e50d-41dc-afed-ed737ce19f9d
                Pashut et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 24 November 2010
                : 10 February 2011
                Page count
                Pages: 18
                Categories
                Research Article
                Biology
                Biophysics
                Biophysics Simulations
                Neuroscience
                Computational Neuroscience
                Single Neuron Function
                Neurophysiology
                Central Nervous System

                Quantitative & Systems biology
                Quantitative & Systems biology

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