Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals.

Published

Journal Article

OBJECTIVE:There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics' vBloc® therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. APPROACH:We developed a two-part computational model, coupling a 3D finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 µm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5-20 kHz), amplitudes (1-8 mA), and electrode designs. MAIN RESULTS:We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed 're-excitation', arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. SIGNIFICANCE:Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our results indicate that compound neural or downstream muscle force recordings may be unreliable as quantitative measures of neural activity for in vivo studies or as biomarkers in closed-loop clinical devices.

Full Text

Duke Authors

Cited Authors

  • Pelot, NA; Behrend, CE; Grill, WM

Published Date

  • August 2017

Published In

Volume / Issue

  • 14 / 4

Start / End Page

  • 046022 -

PubMed ID

  • 28361793

Pubmed Central ID

  • 28361793

Electronic International Standard Serial Number (EISSN)

  • 1741-2552

International Standard Serial Number (ISSN)

  • 1741-2560

Digital Object Identifier (DOI)

  • 10.1088/1741-2552/aa6a5f

Language

  • eng