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Sources of off-target effects of vagus nerve stimulation using the helical clinical lead in domestic pigs.

Publication ,  Journal Article
Nicolai, EN; Settell, ML; Knudsen, BE; McConico, AL; Gosink, BA; Trevathan, JK; Baumgart, IW; Ross, EK; Pelot, NA; Grill, WM; Gustafson, KJ ...
Published in: Journal of neural engineering
July 2020

Clinical data suggest that efficacious vagus nerve stimulation (VNS) is limited by side effects such as cough and dyspnea that have stimulation thresholds lower than those for therapeutic outcomes. VNS side effects are putatively caused by activation of nearby muscles within the neck, via direct muscle activation or activation of nerve fibers innervating those muscles. Our goal was to determine the thresholds at which various VNS-evoked effects occur in the domestic pig—an animal model with vagus anatomy similar to human—using the bipolar helical lead deployed clinically.Intrafascicular electrodes were placed within the vagus nerve to record electroneurographic (ENG) responses, and needle electrodes were placed in the vagal-innervated neck muscles to record electromyographic (EMG) responses.Contraction of the cricoarytenoid muscle occurred at low amplitudes (~0.3 mA) and resulted from activation of motor nerve fibers in the cervical vagus trunk within the electrode cuff which bifurcate into the recurrent laryngeal branch of the vagus. At higher amplitudes (~1.4 mA), contraction of the cricoarytenoid and cricothyroid muscles was generated by current leakage outside the cuff to activate motor nerve fibers running within the nearby superior laryngeal branch of the vagus. Activation of these muscles generated artifacts in the ENG recordings that may be mistaken for compound action potentials representing slowly conducting Aδ-, B-, and C-fibers.Our data resolve conflicting reports of the stimulation amplitudes required for C-fiber activation in large animal studies (>10 mA) and human studies (<250 μA). After removing muscle-generated artifacts, ENG signals with post-stimulus latencies consistent with Aδ- and B-fibers occurred in only a small subset of animals, and these signals had similar thresholds to those that caused bradycardia. By identifying specific neuroanatomical pathways that cause off-target effects and characterizing the stimulation dose-response curves for on- and off-target effects, we hope to guide interpretation and optimization of clinical VNS.

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Published In

Journal of neural engineering

DOI

EISSN

1741-2552

ISSN

1741-2560

Publication Date

July 2020

Volume

17

Issue

4

Start / End Page

046017

Related Subject Headings

  • Vagus Nerve Stimulation
  • Vagus Nerve
  • Swine
  • Sus scrofa
  • Laryngeal Muscles
  • Biomedical Engineering
  • Animals
  • Action Potentials
  • 4003 Biomedical engineering
  • 3209 Neurosciences
 

Citation

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Nicolai, E. N., Settell, M. L., Knudsen, B. E., McConico, A. L., Gosink, B. A., Trevathan, J. K., … Ludwig, K. A. (2020). Sources of off-target effects of vagus nerve stimulation using the helical clinical lead in domestic pigs. Journal of Neural Engineering, 17(4), 046017. https://doi.org/10.1088/1741-2552/ab9db8
Nicolai, Evan N., Megan L. Settell, Bruce E. Knudsen, Andrea L. McConico, Brian A. Gosink, James K. Trevathan, Ian W. Baumgart, et al. “Sources of off-target effects of vagus nerve stimulation using the helical clinical lead in domestic pigs.Journal of Neural Engineering 17, no. 4 (July 2020): 046017. https://doi.org/10.1088/1741-2552/ab9db8.
Nicolai EN, Settell ML, Knudsen BE, McConico AL, Gosink BA, Trevathan JK, et al. Sources of off-target effects of vagus nerve stimulation using the helical clinical lead in domestic pigs. Journal of neural engineering. 2020 Jul;17(4):046017.
Nicolai, Evan N., et al. “Sources of off-target effects of vagus nerve stimulation using the helical clinical lead in domestic pigs.Journal of Neural Engineering, vol. 17, no. 4, July 2020, p. 046017. Epmc, doi:10.1088/1741-2552/ab9db8.
Nicolai EN, Settell ML, Knudsen BE, McConico AL, Gosink BA, Trevathan JK, Baumgart IW, Ross EK, Pelot NA, Grill WM, Gustafson KJ, Shoffstall AJ, Williams JC, Ludwig KA. Sources of off-target effects of vagus nerve stimulation using the helical clinical lead in domestic pigs. Journal of neural engineering. 2020 Jul;17(4):046017.
Journal cover image

Published In

Journal of neural engineering

DOI

EISSN

1741-2552

ISSN

1741-2560

Publication Date

July 2020

Volume

17

Issue

4

Start / End Page

046017

Related Subject Headings

  • Vagus Nerve Stimulation
  • Vagus Nerve
  • Swine
  • Sus scrofa
  • Laryngeal Muscles
  • Biomedical Engineering
  • Animals
  • Action Potentials
  • 4003 Biomedical engineering
  • 3209 Neurosciences