title: High-frequency stimulation of excitable cells and networks.
abstract: High-frequency (HF) stimulation has been shown to block conduction in excitable cells including neurons and cardiac myocytes. However, the precise mechanisms underlying conduction block are unclear. Using a multi-scale method, the influence of HF stimulation is investigated in the simplified FitzhHugh-Nagumo and biophysically-detailed Hodgkin-Huxley models. In both models, HF stimulation alters the amplitude and frequency of repetitive firing in response to a constant applied current and increases the threshold to evoke a single action potential in response to a brief applied current pulse. Further, the excitable cells cannot evoke a single action potential or fire repetitively above critical values for the HF stimulation amplitude. Analytical expressions for the critical values and thresholds are determined in the FitzHugh-Nagumo model. In the Hodgkin-Huxley model, it is shown that HF stimulation alters the dynamics of ionic current gating, shifting the steady-state activation, inactivation, and time constant curves, suggesting several possible mechanisms for conduction block. Finally, we demonstrate that HF stimulation of a network of neurons reduces the electrical activity firing rate, increases network synchronization, and for a sufficiently large HF stimulation, leads to complete electrical quiescence. In this study, we demonstrate a novel approach to investigate HF stimulation in biophysically-detailed ionic models of excitable cells, demonstrate possible mechanisms for HF stimulation conduction block in neurons, and provide insight into the influence of HF stimulation on neural networks.
authors.affiliation: Department of Applied Science, The College of William and Mary, Williamsburg, Virginia, United States of America.
authors.forename: Seth H
authors.initials: SH
authors.lastname: Weinberg
mesh_terms: D000200:Action Potentials; D000465:Algorithms; D000818:Animals; D004558:Electric Stimulation; D006801:Humans; D008959:Models, Neurological; D009431:Neural Conduction; D009434:Neural Pathways; D009474:Neurons / Q000502:physiology*; D015203:Reproducibility of Results