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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Peña, E; Pelot, NA; Grill, WM

Published Date

  • March 3, 2021

Published In

Volume / Issue

  • 11 / 1

Start / End Page

  • 5077 -

PubMed ID

  • 33658552

Pubmed Central ID

  • 33658552

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

International Standard Serial Number (ISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-021-84503-3

Language

  • eng