Mechanisms of magnetic stimulation of central nervous system neurons

Autor: Izhar Bar-Gad, Shuki Wolfus, Alon Korngreen, Alex Friedman, Yosef Yeshurun, Tamar Pashut, Michal Lavidor
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: PLoS Computational Biology, Vol 7, Iss 3, p e1002022 (2011)
PLoS Computational Biology
ISSN: 1553-7358
Popis: 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.
Databáze: OpenAIRE
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