Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations

Bashar W Badran, Alfred B Yu, Devin Adair, Georgia Mappin, William H DeVries, Dorothea D Jenkins, Mark S George, Marom Bikson, Bashar W Badran, Alfred B Yu, Devin Adair, Georgia Mappin, William H DeVries, Dorothea D Jenkins, Mark S George, Marom Bikson

Abstract

Non-invasive vagus nerve stimulation (VNS) may be administered via a novel, emerging neuromodulatory technique known as transcutaneous auricular vagus nerve stimulation (taVNS). Unlike cervically-implanted VNS, taVNS is an inexpensive and non-surgical method used to modulate the vagus system. taVNS is appealing as it allows for rapid translation of basic VNS research and serves as a safe, inexpensive, and portable neurostimulation system for the future treatment of central and peripheral disease. The background and rationale for taVNS is described, along with electrical and parametric considerations, proper ear targeting and attachment of stimulation electrodes, individual dosing via determination of perception threshold (PT), and safe administration of taVNS.

Figures

Figure 1:. Vagus Nerve Efferent Projections and…
Figure 1:. Vagus Nerve Efferent Projections and Cross-section.
(A) Efferent projections of the vagus nerve target every major organ on the body with wide effects on bodily function (B) Cross-section of the vagus nerve, demonstrating the inside anatomy of the nerve as a series of bundles of nerves all contained within one major pathway.
Figure 2:. taVNS Ear Targets.
Figure 2:. taVNS Ear Targets.
Targeting the ABVN can be accomplished by stimulating the anterior wall of the outer ear canal, landmarked notably by the tragus (A1), or cymba conchae (A2). Sham stimulation is administered to the earlobe (S).
Figure 3:. Key Components.
Figure 3:. Key Components.
The minimum required components for proper administration of taVNS are the following (A) ear stimulation electrodes, (B) conductive gel and alcohol prep pads, (C) computer capable of sending and receiving TTL pulses to a (D) constant current stimulator to trigger stimulation.
Figure 4:. Example Setup.
Figure 4:. Example Setup.
This photo shows an individual receiving taVNS of the left ear while in position to undergo an experimental paradigm.
Figure 5:
Figure 5:
Screenshot of the GUI used for stimulation.
Figure 6:. Electrical Stimulation Waveform Manipulations.
Figure 6:. Electrical Stimulation Waveform Manipulations.
Direct square wave electrical current can be delivered at various parameters. This figure demonstrates key properties of the waveform that can be changed in order to achieve desired biologic effects.
Figure 7:. Perceptual Threshold Values at Increasing…
Figure 7:. Perceptual Threshold Values at Increasing Pulse Widths.
As pulse width increases, perceptual threshold (PT) decreases. Most healthy individuals will have a PT within 2 standard deviations (SD) of these mean values.

References

    1. Berthoud HR, & Neuhuber WL Functional and chemical anatomy of the afferent vagal system. Autonomic Neuroscience. 85 (1–3), 1–17 (2000).
    1. George MS et al. Vagus nerve stimulation: a new form of therapeutic Brain Stimulation. CNS Spectrums. 5 (11), 43–52 (2000).
    1. Nemeroff CB et al. VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology. 31 (7), 1345–1355 (2006).
    1. Ventureyra EC Transcutaneous vagus nerve stimulation for partial onset seizure therapy. Child’s Nervous System. 16 (2), 101–102 (2000).
    1. Peuker ET, & Filler TJ The nerve supply of the human auricle. Clinical Anatomy. 15 (1), 35–37 (2002).
    1. Kreuzer PM et al. Transcutaneous vagus nerve stimulation: retrospective assessment of cardiac safety in a pilot study. Frontiers in Psychiatry. 3, 70(2012).
    1. Kreuzer PM et al. Feasibility, safety and efficacy of transcutaneous vagus nerve stimulation in chronic tinnitus: an open pilot study. Brain Stimulation. 7 (5), 740–747 (2014).
    1. Badran BW et al. Short trains of transcutaneous auricular vagus nerve stimulation (taVNS) have parameter-specific effects on heart rate. Brain Stimulation. 11 (4), 699–708 (2018).
    1. Badran BW et al. Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review. Brain Stimulation. 11 (3), 492–500 (2018).
    1. Clancy JA et al. Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity. Brain Stimulation. 7 (6), 871–877 (2014).
    1. Usichenko T, Hacker H, & Lotze M Transcutaneous auricular vagal nerve stimulation (taVNS) might be a mechanism behind the analgesic effects of auricular acupuncture. Brain Stimulation. 10 (6), 1042–1044 (2017).
    1. Rong P et al. Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: A nonrandomized controlled pilot study. Journal of Affective Disorders. 195, 172–179 (2016).
    1. Bauer S et al. Transcutaneous vagus nerve stimulation (tVNS) for treatment of drug-resistant epilepsy: a randomized, double-blind clinical trial (cMPsE02). Brain Stimulation. 9 (3), 356–363 (2016).
    1. Jacobs HI, Riphagen JM, Razat CM, Wiese S, & Sack AT Transcutaneous vagus nerve stimulation boosts associative memory in older individuals. Neurobiology of Aging. 36 (5), 1860–1867 (2015).
    1. Jongkees BJ, Immink MA, Finisguerra A, & Colzato LS Transcutaneous Vagus Nerve Stimulation (tVNS) Enhances Response Selection During Sequential Action. Frontiers in Psychology. 9, 1159(2018).
    1. Sellaro R, de Gelder B, Finisguerra A, & Colzato LS Transcutaneous vagus nerve stimulation (tVNS) enhances recognition of emotions in faces but not bodies. Cortex. 99, 213–223 (2018).
    1. Jin Y, & Kong J Transcutaneous vagus nerve stimulation: a promising method for treatment of autism spectrum disorders. Frontiers in Neuroscience. 10 (2016).
    1. Colzato LS, Ritter SM, & Steenbergen L Transcutaneous vagus nerve stimulation (tVNS) enhances divergent thinking. Neuropsychologia. 111, 72–76 (2018).
    1. George MS et al. Vagus nerve stimulation for the treatment of depression and other neuropsychiatric disorders. Expert Review of Neurotherapeutics. 7 (1), 63–74 (2007).
    1. Kong J, Fang J, Park J, Li S, & Rong P Treating Depression with Transcutaneous Auricular Vagus Nerve Stimulation: State of the Art and Future Perspectives. Frontiers in Psychiatry. 9, 20(2018).
    1. Dawson J et al. Safety, feasibility, and efficacy of vagus nerve stimulation paired with upper-limb rehabilitation after ischemic stroke. Stroke. 47 (1), 143–150 (2016).
    1. Liu H et al. Vagus nerve stimulation inhibits heroin-seeking behavior induced by heroin priming or heroin-associated cues in rats. Neuroscience Letters. 494 (1), 70–74 (2011).
    1. Zhang Y et al. Chronic Vagus Nerve Stimulation Improves Autonomic Control and Attenuates Systemic Inflammation and Heart Failure Progression in a Canine High-Rate Pacing ModelCLINICAL PERSPECTIVE. Circulation: Heart Failure. 2 (6), 692–699 (2009).
    1. De Ridder D, Kilgard M, Engineer N, & Vanneste S Placebo-controlled vagus nerve stimulation paired with tones in a patient with refractory tinnitus: a case report. Otology & Neurotology. 36 (4), 575–580 (2015).
    1. Shim HJ et al. Feasibility and safety of transcutaneous vagus nerve stimulation paired with notched music therapy for the treatment of chronic tinnitus. Journal of Audiology & Otology. 19 (3), 159–167 (2015).
    1. Chesterton LS, Foster NE, Wright CC, Baxter GD, & Barlas P Effects of TENS frequency, intensity and stimulation site parameter manipulation on pressure pain thresholds in healthy human subjects. Pain. 106 (1–2), 73–80 (2003).
    1. Badran BW et al. Tragus or cymba conchae? Investigating the anatomical foundation of transcutaneous auricular vagus nerve stimulation (taVNS). Brain Stimulation. 11 (4), 947–948 (2018).
    1. Ramsay RE et al. Vagus nerve stimulation for treatment of partial seizures: 2. Safety, side effects, and tolerability. First International Vagus Nerve Stimulation Study Group. Epilepsia. 35 (3), 627–636 (1994).
    1. Farrar JT, Young JP Jr., LaMoreaux L, Werth JL, & Poole RM Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 94 (2), 149–158 (2001).
    1. Badran BW et al. Short trains of transcutaneous auricular vagus nerve stimulation (taVNS) have parameter-specific effects on heart rate. Brain Stimulation. (2018).
    1. Bauer S et al. Transcutaneous Vagus Nerve Stimulation (tVNS) for Treatment of Drug-Resistant Epilepsy: A Randomized, Double-Blind Clinical Trial (cMPsE02). Brain Stimulation. 9 (3), 356–363 (2016).
    1. Bikson M et al. Limited output transcranial electrical stimulation (LOTES-2017): Engineering principles, regulatory statutes, and industry standards for wellness, over-the-counter, or prescription devices with low risk. Brain Stimulation. 11 (1), 134–157 (2018).
    1. Kraus T et al. BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation. Journal of Neural Transmission. 114 (11), 1485–1493 (2007).
    1. Kraus T et al. CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal-a pilot study. Brain Stimulation. 6 (5), 798–804 (2013).
    1. Fallgatter A et al. Far field potentials from the brain stem after transcutaneous vagus nerve stimulation. Journal of Neural Transmission. 110(12), 1437–1443 (2003).
    1. Fallgatter AJ, Ehlis A-C, Ringel TM, & Herrmann MJ Age effect on far field potentials from the brain stem after transcutaneous vagus nerve stimulation. International Journal of Psychophysiology. 56 (1), 37–43 (2005).
    1. Polak T et al. Far field potentials from brain stem after transcutaneous vagus nerve stimulation: optimization of stimulation and recording parameters. Journal of Neural Transmission. 116 (10), 1237–1242 (2009).
    1. Greif R et al. Transcutaneous electrical stimulation of an auricular acupuncture point decreases anesthetic requirement. The Journal of the American Society of Anesthesiologists. 96 (2), 306–312 (2002).
    1. Wang S-M, Peloquin C, & Kain ZN The use of auricular acupuncture to reduce preoperative anxiety. Anesthesia & Analgesia. 93 (5), 1178–1180 (2001).
    1. Badran BW et al. Transcutaneous auricular vagus nerve stimulation (taVNS) for improving oromotor function in newborns. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation. (2018).
    1. Borovikova LV et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 405 (6785), 458–462 (2000).
    1. Ulloa L The vagus nerve and the nicotinic anti-inflammatory pathway. Nature Reviews Drug Discovery. 4 (8), 673–684 (2005).

Source: PubMed

3
Sottoscrivi