Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance

Abstract Reversible block of nerve conduction using kilohertz frequency electrical signals has substantial potential for treatment of disease. However, the ability to block nerve fibers selectively is limited by poor understanding of the relationship between waveform parameters and the nerve fibers...

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Autores principales:	Edgar Peña, Nicole A. Pelot, Warren M. Grill
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e21434f7774e4f1c92218e510af6ce71
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spelling	oai:doaj.org-article:e21434f7774e4f1c92218e510af6ce712021-12-02T15:53:46ZNon-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance10.1038/s41598-021-84503-32045-2322https://doaj.org/article/e21434f7774e4f1c92218e510af6ce712021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84503-3https://doaj.org/toc/2045-2322Abstract Reversible block of nerve conduction using kilohertz frequency electrical signals has substantial potential for treatment of disease. However, the ability to block nerve fibers selectively is limited by poor understanding of the relationship between waveform parameters and the nerve fibers that are blocked. Previous in vivo studies reported non-monotonic relationships between block signal frequency and block threshold, suggesting the potential for fiber-selective block. However, the mechanisms of non-monotonic block thresholds were unclear, and these findings were not replicated in a subsequent in vivo study. We used high-fidelity computational models and in vivo experiments in anesthetized rats to show that non-monotonic threshold-frequency relationships do occur, that they result from amplitude- and frequency-dependent charge imbalances that cause a shift between kilohertz frequency and direct current block regimes, and that these relationships can differ across fiber diameters such that smaller fibers can be blocked at lower thresholds than larger fibers. These results reconcile previous contradictory studies, clarify the mechanisms of interaction between kilohertz frequency and direct current block, and demonstrate the potential for selective block of small fiber diameters.Edgar PeñaNicole A. PelotWarren M. GrillNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Edgar Peña Nicole A. Pelot Warren M. Grill Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance
description	Abstract Reversible block of nerve conduction using kilohertz frequency electrical signals has substantial potential for treatment of disease. However, the ability to block nerve fibers selectively is limited by poor understanding of the relationship between waveform parameters and the nerve fibers that are blocked. Previous in vivo studies reported non-monotonic relationships between block signal frequency and block threshold, suggesting the potential for fiber-selective block. However, the mechanisms of non-monotonic block thresholds were unclear, and these findings were not replicated in a subsequent in vivo study. We used high-fidelity computational models and in vivo experiments in anesthetized rats to show that non-monotonic threshold-frequency relationships do occur, that they result from amplitude- and frequency-dependent charge imbalances that cause a shift between kilohertz frequency and direct current block regimes, and that these relationships can differ across fiber diameters such that smaller fibers can be blocked at lower thresholds than larger fibers. These results reconcile previous contradictory studies, clarify the mechanisms of interaction between kilohertz frequency and direct current block, and demonstrate the potential for selective block of small fiber diameters.
format	article
author	Edgar Peña Nicole A. Pelot Warren M. Grill
author_facet	Edgar Peña Nicole A. Pelot Warren M. Grill
author_sort	Edgar Peña
title	Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance
title_short	Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance
title_full	Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance
title_fullStr	Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance
title_full_unstemmed	Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance
title_sort	non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e21434f7774e4f1c92218e510af6ce71
work_keys_str_mv	AT edgarpena nonmonotonickilohertzfrequencyneuralblockthresholdsarisefromamplitudeandfrequencydependentchargeimbalance AT nicoleapelot nonmonotonickilohertzfrequencyneuralblockthresholdsarisefromamplitudeandfrequencydependentchargeimbalance AT warrenmgrill nonmonotonickilohertzfrequencyneuralblockthresholdsarisefromamplitudeandfrequencydependentchargeimbalance
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Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance

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