Critical Review of Transcutaneous Vagus Nerve Stimulation: Challenges for Translation to Clinical Practice

Jonathan Y Y Yap, Charlotte Keatch, Elisabeth Lambert, Will Woods, Paul R Stoddart, Tatiana Kameneva, Jonathan Y Y Yap, Charlotte Keatch, Elisabeth Lambert, Will Woods, Paul R Stoddart, Tatiana Kameneva

Abstract

Several studies have illustrated that transcutaneous vagus nerve stimulation (tVNS) can elicit therapeutic effects that are similar to those produced by its invasive counterpart, vagus nerve stimulation (VNS). VNS is an FDA-approved therapy for the treatment of both depression and epilepsy, but it is limited to the management of more severe, intervention-resistant cases as a second or third-line treatment option due to perioperative risks involved with device implantation. In contrast, tVNS is a non-invasive technique that involves the application of electrical currents through surface electrodes at select locations, most commonly targeting the auricular branch of the vagus nerve (ABVN) and the cervical branch of the vagus nerve in the neck. Although it has been shown that tVNS elicits hypo- and hyperactivation in various regions of the brain associated with anxiety and mood regulation, the mechanism of action and influence of stimulation parameters on clinical outcomes remains predominantly hypothetical. Suppositions are largely based on correlations between the neurobiology of the vagus nerve and its effects on neural activity. However, tVNS has also been investigated for several other disorders, including tinnitus, migraine and pain, by targeting the vagus nerve at sites in both the ear and the neck. As most of the described methods differ in the parameters and protocols applied, there is currently no firm evidence on the optimal location for tVNS or the stimulation parameters that provide the greatest therapeutic effects for a specific condition. This review presents the current status of tVNS with a focus on stimulation parameters, stimulation sites, and available devices. For tVNS to reach its full potential as a non-invasive and clinically relevant therapy, it is imperative that systematic studies be undertaken to reveal the mechanism of action and optimal stimulation modalities.

Keywords: neuromodulation; neurostimulation; transcutaneous; vagus nerve; vagus nerve stimulation.

Copyright © 2020 Yap, Keatch, Lambert, Woods, Stoddart and Kameneva.

Figures

Figure 1
Figure 1
(A) Ear regions with innervation by the cutaneous auricular branch of the vagus nerve (ABVN). (B) Nerves in the neck region including cervical branch of the vagus nerve.
Figure 2
Figure 2
Innervation of the auricular branch of the vagus nerve (ABVN). GAN, great auricular nerve; ATN, auriculotemporal nerve; STA, superficial temporal artery; LON, lesser occipital nerve; V, vessels. Adapted from Peuker and Filler (2002) with permission.
Figure 3
Figure 3
Topography of vagus nerve anatomy in the neck. Blue arrows indicate vessels external to the epineurium. Adapted from Hammer et al. (2018) with permission.
Figure 4
Figure 4
(A) Cerbomed NEMOS. Adapted from www.cerbomed.com. (B). Electrocore gammaCore. Adapted from www.gammacore.com.
Figure 5
Figure 5
Stimulation electrode positions. (A) Neck stimulation using a gammaCore device (Silberstein et al., 2016b). Image courtesy of electroCore Inc, electrocore.com. (B) Earlobe sham and cymba concha stimulation using NEMOS electrodes (Frangos et al., 2015). (C) External ear canal and concha stimulation using a TENS device from Suzhou (Liu et al., 2018). (D) Tragus stimulation (Lehtimäki et al., 2013). (E) External ear canal stimulation using a headset NET-1000 (Hein et al., 2012). Image courtesy of Auri-Stim Medical Inc, net1device.com. (F) Concha and cymba concha active stimulation (Rong et al., 2016). All figures reproduced with permission.

References

    1. Agnew W. F., McCreery D. B. (1990). Considerations for safety with chronically implanted nerve electrodes. Epilepsia 31, S27–S32. 10.1111/j.1528-1157.1990.tb05845.x
    1. Aihua L., Lu S., Liping L., Xiuru W., Hua L., Yuping W. (2014). A controlled trial of transcutaneous vagus nerve stimulation for the treatment of pharmacoresistant epilepsy. Epilepsy Behav. 39, 105–110. 10.1016/j.yebeh.2014.08.005
    1. Altavilla R., Paolucci M., Altamura C., Vernieri F. (2015). P038. Effects of non-invasive vagus nerve stimulation on cerebral vasomotor reactivity in patients with chronic migraine during intercritical phase: a pilot study. J. Headache Pain 16:A62. 10.1186/1129-2377-16-S1-A62
    1. Ardell J. L., Randall W. C. (1986). Selective vagal innervation of sinoatrial and atrioventricular nodes in canine heart. Am. J. Physiol. Heart Circ. Physiol. 251, H764–H773. 10.1152/ajpheart.1986.251.4.H764
    1. Assenza G., Campana C., Colicchio G., Tombini M., Assenza F., Di Pino G., et al. . (2017). Transcutaneous and invasive vagal nerve stimulations engage the same neural pathways: in-vivo human evidence. Brain Stimul. 10, 853–854. 10.1016/j.brs.2017.03.005
    1. Badran B. W., Dowdle L. T., Mithoefer O. J., LaBate N. T., Coatsworth J., Brown J. C., et al. . (2018a). Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: a concurrent taVNS/fMRI study and review. Brain Stimul. 11, 492–500. 10.1016/j.brs.2017.12.009
    1. Badran B. W., Jenkins D. D., DeVries W. H., Dancy M., Summers P. M., Mappin G. M., et al. . (2018b). Transcutaneous auricular vagus nerve stimulation (taVNS) for improving oromotor function in newborns. Brain Stimul. 11, 1198–1200. 10.1016/j.brs.2018.06.009
    1. Baillet S. (2017). Magnetoencephalography for brain electrophysiology and imaging. Nat. Neurosci. 20, 327–339. 10.1038/nn.4504
    1. Barbanti P., Grazzi L., Egeo G., Maria Padovan A., Liebler E., Bussone G. (2015). Non-invasive vagus nerve stimulation for acute treatment of high-frequency and chronic migraine: an open-label study. J. Headache Pain 16:61. 10.1186/s10194-015-0542-4
    1. Bauer S., Baier H., Baumgartner C., Bohlmann K., Fauser S., Graf W., et al. . (2016). Transcutaneous vagus nerve stimulation (tVNS) for treatment of drug-resistant epilepsy: a randomized, double-blind clinical trial (cMPsE02). Brain Stimul. 9, 356–363. 10.1016/j.brs.2015.11.003
    1. Beghi E. (2019). Global, regional, and national burden of epilepsy, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 18, 357–375. 10.1016/S1474-4422(18)30454-X
    1. Ben-Menachem E., Hamberger A., Hedner T., Hammond E., Uthman B., Slater J., et al. . (1995). Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. Epilepsy Res. 20, 221–227. 10.1016/0920-1211(94)00083-9
    1. Bikson M., Bestmann S., Edwards D. (2013). Transcranial devices are not playthings. Nature 501, 167–167. 10.1038/501167b
    1. Boon P., Vonck K., van Rijckevorsel K., Tahry R. E., Elger C. E., Mullatti N., et al. . (2015). A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation. Seizure 32, 52–61. 10.1016/j.seizure.2015.08.011
    1. Burger A. M., Verkuil B. (2018). Transcutaneous nerve stimulation via the tragus: are we really stimulating the vagus nerve? Brain Stimul. 11, 945–946. 10.1016/j.brs.2018.03.018
    1. Burger A. M., Verkuil B., Van Diest I., Van der Does W., Thayer J. F., Brosschot J. F. (2016). The effects of transcutaneous vagus nerve stimulation on conditioned fear extinction in humans. Neurobiol. Learn. Mem. 132, 49–56. 10.1016/j.nlm.2016.05.007
    1. Busch V., Zeman F., Heckel A., Menne F., Ellrich J., Eichhammer P. (2013). The effect of transcutaneous vagus nerve stimulation on pain perception–an experimental study. Brain Stimul. 6, 202–209. 10.1016/j.brs.2012.04.006
    1. Butt M. F., Albusoda A., Farmer A. D., Aziz Q. (2019). The anatomical basis for transcutaneous auricular vagus nerve stimulation. J. Anat. 236, 588–611. 10.1111/joa.13122
    1. Capone F., Assenza G., Di Pino G., Musumeci G., Ranieri F., Florio L., et al. . (2015). The effect of transcutaneous vagus nerve stimulation on cortical excitability. J. Neural Transm. 122, 679–685. 10.1007/s00702-014-1299-7
    1. Cha W. W., Song K., Lee H. Y. (2016). Persistent geotropic direction-changing positional nystagmus treated with transcutaneous vagus nerve stimulation. Brain Stimul. 9, 469–470. 10.1016/j.brs.2016.03.011
    1. Chae J. H., Nahas Z., Lomarev M., Denslow S., Lorberbaum J. P., Bohning D. E., et al. . (2003). A review of functional neuroimaging studies of vagus nerve stimulation (VNS). J. Psychiatr. Res. 37, 443–455. 10.1016/S0022-3956(03)00074-8
    1. Chen M., Yu L., Ouyang F., Liu Q., Wang Z., Wang S., et al. (2015). The right side or left side of noninvasive transcutaneous vagus nerve stimulation: based on conventional wisdom or scientific evidence? Int. J. Cardiol. 187, 44–45. 10.1016/j.ijcard.2015.03.351
    1. Clancy J. A., Mary D. A., Witte K. K., Greenwood J. P., Deuchars S. A., Deuchars J. (2014). Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity. Brain Stimul. 7, 871–877. 10.1016/j.brs.2014.07.031
    1. Colzato L. S., Ritter S. M., Steenbergen L. (2018). Transcutaneous vagus nerve stimulation (tVNS) enhances divergent thinking. Neuropsychologia 111, 72–76. 10.1016/j.neuropsychologia.2018.01.003
    1. Coppola G., Vandenheede M., Di Clemente L., Ambrosini A., Fumal A., De Pasqua V., et al. . (2004). Somatosensory evoked high-frequency oscillations reflecting thalamo-cortical activity are decreased in migraine patients between attacks. Brain 128, 98–103. 10.1093/brain/awh334
    1. Depression Physician's Manual (2005). Depression Physician's Manual: VNS Therapy Pulse Model 102 Generator and VNS Therapy Pulse Duo Model 102R Generator.
    1. Dietrich S., Smith J., Scherzinger C., Hofmann-Preiß K., Freitag T., Eisenkolb A., et al. . (2008). A novel transcutaneous vagus nerve stimulation leads to brainstem and cerebral activations measured by functional MRI [Funktionelle Magnetresonanztomographie zeigt Aktivierungen des Hirnstamms und weiterer zerebraler Strukturen unter transkutaner Vagusne]. Biomed. Eng. 53, 104–111. 10.1515/BMT.2008.022
    1. Dorr A. E., Debonnel G. (2006). Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission. J. Pharmacol. Exp. Ther. 318, 890–898. 10.1124/jpet.106.104166
    1. ElectroCore I. (2018). Instructions for Use for gammaCore SapphireTM(Non-invasive Vagus Nerve Stimulator). Technical report, tVNS device GammaCore, electroCore Inc.
    1. Engineer N. D., Riley J. R., Seale J. D., Vrana W. A., Shetake J. A., Sudanagunta S. P., et al. . (2011). Reversing pathological neural activity using targeted plasticity. Nature 470, 101–104. 10.1038/nature09656
    1. Evans M. S., Verma-Ahuja S., Naritoku D. K., Espinosa J. A. (2004). Intraoperative human vagus nerve compound action potentials. Acta Neurol. Scand. 110, 232–238. 10.1111/j.1600-0404.2004.00309.x
    1. Fahy B. G. (2010). Intraoperative and perioperative complications with a vagus nerve stimulation device. J. Clin. Anesth. 22, 213–222. 10.1016/j.jclinane.2009.10.002
    1. Fallgatter A. J., Neuhauser B., Herrmann M. J., Ehlis A.-C., Wagener A., Scheuerpflug P., et al. . (2003). Far field potentials from the brain stem after transcutaneous vagus nerve stimulation. J. Neural Transm. 110, 1437–1443. 10.1007/s00702-003-0087-6
    1. Fang J., Egorova N., Rong P. (2017). Early cortical biomarkers of longitudinal transcutaneous vagus nerve stimulation treatment success in depression. Neuroimage Clin. 14, 105–111. 10.1016/j.nicl.2016.12.016
    1. Fang J., Rong P., Hong Y., Fan Y., Liu J., Wang H., et al. . (2016). Transcutaneous vagus nerve stimulation modulates default mode network in major depressive disorder. Biol. Psychiatry 79, 266–273. 10.1016/j.biopsych.2015.03.025
    1. Fischer R., Ventura-Bort C., Hamm A., Weymar M. (2018). Transcutaneous vagus nerve stimulation (tVNS) enhances conflict-triggered adjustment of cognitive control. Cogn. Affect. Behav. Neurosci. 18, 680–693. 10.3758/s13415-018-0596-2
    1. Fisher R. S., Afra P., Macken M., Minecan D. N., Bagić A., Benbadis S. R., et al. . (2016). Automatic vagus nerve stimulation triggered by ictal tachycardia: clinical outcomes and device performance-the U.S. E-37 trial. Neuromodulation 19, 188–195. 10.1111/ner.12376
    1. Fitzgerald P. B., Jessica Benitez F., Anthony de Castella G., Jeff Daskalakis D. Z., Kulkarni J. (2006). A Randomized, Controlled Trial of Sequential Bilateral Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression. Technical report.
    1. Fix J. D., Brueckner J. K. (2009). High-Yield Neuroanatomy. Philadelphia, PA: Wolters Kluwer Health; Lippincott Williams & Wilkins.
    1. Frangos E., Ellrich J., Komisaruk B. R. (2015). Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: fMRI evidence in humans. Brain Stimul. 8, 624–636. 10.1016/j.brs.2014.11.018
    1. Frokaer J. B., Bergmann S., Brock C., Madzak A., Farmer A. D., Ellrich J., et al. (2016). Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity. Neurogastroenterol. Motil. 28, 592–598. 10.1111/nmo.12760
    1. Gaul C., Diener H.-C., Silver N., Magis D., Reuter U., Andersson A., et al. . (2016). Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): a randomised controlled study. Cephalalgia 36, 534–546. 10.1177/0333102415607070
    1. Goadsby P., Grosberg B., Mauskop A., Cady R., Simmons K. (2014). Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study. Cephalalgia 34, 986–993. 10.1177/0333102414524494
    1. Grazzi L., Egeo G., Calhoun A. H., McClure C. K., Liebler E., Barbanti P. (2016). Non-invasive vagus nerve stimulation (nVNS) as mini-prophylaxis for menstrual/menstrually related migraine: an open-label study. J. Headache Pain 17:91. 10.1186/s10194-016-0684-z
    1. Grazzi L., Usai S., Bussone G. (2014). Gammacore device for treatment of migraine attack: preliminary report. J. Headache Pain 15:G12 10.1186/1129-2377-15-S1-G12
    1. Groves D. A., Brown V. J. (2005). Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects. Neurosci. Biobehav. Rev. 29, 493–500. 10.1016/j.neubiorev.2005.01.004
    1. Gupta D., Verma S., Vishwakarma S. (1986). Anatomic basis of Arnold's ear-cough reflex. Surg. Radiol. Anat. 8, 217–220. 10.1007/BF02425070
    1. Hammer N., Löffler S., Cakmak Y. O., Ondruschka B., Planitzer U., Schultz M., et al. . (2018). Cervical vagus nerve morphometry and vascularity in the context of nerve stimulation–a cadaveric study. Nat. Sci. Rep. 8:7997. 10.1038/s41598-018-26135-8
    1. Han B. I., Lee H. W., Kim T. Y., Lim J. S., Shin K. S. (2009). Tinnitus: characteristics, causes, mechanisms, and treatments. J. Clin. Neurol. 5:11. 10.3988/jcn.2009.5.1.11
    1. Handforth A., DeGiorgio C. M., Schachter S. C., Uthman B. M., Naritoku D. K., Tecoma E. S., et al. . (1998). Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 51, 48–55. 10.1212/WNL.51.1.48
    1. Hasan A., Wolff-Menzler C., Pfeiffer S., Falkai P., Weidinger E., Jobst A., et al. . (2015). Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized controlled pilot study. Eur. Archiv. Psychiatry Clin. Neurosci. 265, 589–600. 10.1007/s00406-015-0618-9
    1. He W., Jing X., Wang X., Rong P., Li L., Shi H., et al. . (2013). Transcutaneous auricular vagus nerve stimulation as a complementary therapy for pediatric epilepsy: a pilot trial. Epilepsy Behav. 28, 343–346. 10.1016/j.yebeh.2013.02.001
    1. He W., Wang X., Shi H., Shang H., Li L., Jing X., et al. . (2012). Auricular acupuncture and vagal regulation. Evid. Based Complement. Altern. Med. 2012, 1–6. 10.1155/2012/615476
    1. He W., Zhu B., Rong P. (2009). A new concept of transcutaneous vagus nerve stimulation for epileptic seizure. Abstr. Soc. Neurosci. 539. 10.1155/2012/786839
    1. Hein E., Nowak M., Kiess O., Biermann T., Bayerlein K., Kornhuber J., et al. . (2012). Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. J. Neural Transm. 120, 821–827. 10.1007/s00702-012-0908-6
    1. Helmers S. L., Begnaud J., Cowley A., Corwin H. M., Edwards J. C., Holder D. L., et al. . (2012). Application of a computational model of vagus nerve stimulation. Acta Neurol. Scand. 126, 336–343. 10.1111/j.1600-0404.2012.01656.x
    1. Henry T. R. (2002). Therapeutic mechanisms of vagus nerve stimulation. Neurology 59, S3–S14. 10.1212/WNL.59.6_suppl_4.S3
    1. Henry T. R., Bakay R. A. E., Votaw J. R., Pennell P. B., Epstein C. M., Faber T. L., et al. . (1998). Brain blood flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: I. Acute effects at high and low levels of stimulation. Epilepsia 39, 983–990. 10.1111/j.1528-1157.1998.tb01448.x
    1. Huang F., Dong J., Kong J., Wang H., Meng H., Spaeth R. B., et al. . (2014). Effect of transcutaneous auricular vagus nerve stimulation on impaired glucose tolerance: a pilot randomized study. BMC Complement. Altern. Med. 14:203. 10.1186/1472-6882-14-203
    1. Hyvärinen P., Yrttiaho S., Lehtimäki J., Ilmoniemi R. J., Mäkitie A., Ylikoski J., et al. . (2015). Transcutaneous vagus nerve stimulation modulates tinnitus-related beta- and gamma-band activity. Ear Hear. 36, e76–e85. 10.1097/AUD.0000000000000123
    1. Iriarte J., Urrestarazu E., Alegre M., Macías A., Gómez A., Amaro P., et al. . (2009). Late-onset periodic asystolia during vagus nerve stimulation. Epilepsia 50, 928–932. 10.1111/j.1528-1167.2008.01918.x
    1. Jacobs H. I., Riphagen J. M., Razat C. M., Wiese S., Sack A. T. (2015). Transcutaneous vagus nerve stimulation boosts associative memory in older individuals. Neurobiol. Aging 36, 1860–1867. 10.1016/j.neurobiolaging.2015.02.023
    1. Johnson M., Hajela V., Ashton C., Thompson J. (1991). The effects of auricular transcutaneous electrical nerve stimulation (TENS) on experimental pain threshold and autonomic function in healthy subjects. Pain 46, 337–342. 10.1016/0304-3959(91)90116-F
    1. Johnson R. L., Wilson C. G. (2018). A review of vagus nerve stimulation as a therapeutic intervention. J. Inflamm. Res. 11, 203–213. 10.2147/JIR.S163248
    1. Jongkees B. J., Immink M. A., Finisguerra A., Colzato L. S. (2018). Transcutaneous vagus nerve stimulation (tVNS) enhances response selection during sequential action. Front. Psychol. 9:1159. 10.3389/fpsyg.2018.01159
    1. Kaniusas E., Kampusch S., Tittgemeyer M., Panetsos F., Gines R. F., Papa M., et al. . (2019a). Current directions in the auricular vagus nerve stimulation II–an engineering perspective. Front. Neurosci. 13:772. 10.3389/fnins.2019.00772
    1. Kaniusas E., Kampusch S., Tittgemeyer M., Panetsos F., Gines R. F., Papa M., et al. . (2019b). Current directions in the auricular vagus nerve stimulation I–a physiological perspective. Front. Neurosci. 13:854. 10.3389/fnins.2019.00854
    1. Keute M., Boehrer L., Ruhnau P., Heinze H.-J., Zaehle T. (2019). Transcutaneous vagus nerve stimulation (tVNS) and the dynamics of visual bistable perception. Front. Neurosci. 13:227. 10.3389/fnins.2019.00227
    1. Keute M., Ruhnau P., Heinze H. J., Zaehle T. (2018). Behavioral and electrophysiological evidence for GABAergic modulation through transcutaneous vagus nerve stimulation. Clin. Neurophysiol. 129, 1789–1795. 10.1016/j.clinph.2018.05.026
    1. Kinfe T. M., Pintea B., Güresir E., Vatter H. (2015a). Partial response of intractable cluster-Tic syndrome treated by cervical non-invasive vagal nerve stimulation (nVNS). Brain Stimul. 8, 669–671. 10.1016/j.brs.2015.01.002
    1. Kinfe T. M., Pintea B., Muhammad S., Zaremba S., Roeske S., Simon B. J., et al. (2015b). Cervical non-invasive vagus nerve stimulation (nVNS) for preventive and acute treatment of episodic and chronic migraine and migraine-associated sleep disturbance: preliminary findings from a prospective observational cohort study. J. Headache Pain 16:101 10.1186/s10194-015-0582-9
    1. Kiyokawa J., Yamaguchi K., Okada R., Maehara T., Akita K. (2014). Origin, course and distribution of the nerves to the posterosuperior wall of the external acoustic meatus. Anat. Sci. Int. 89, 238–245. 10.1007/s12565-014-0231-4
    1. Krahl S. (2012). Vagus nerve stimulation for epilepsy: a review of the peripheral mechanisms. Surg. Neurol. Int. 3:47. 10.4103/2152-7806.103015
    1. Krahl S. E., Clark K. B., Smith D. C., Browning R. A. (1998). Locus coeruleus lesions suppress the seizure-attenuating effects of vagus nerve stimulation. Epilepsia 39, 709–714. 10.1111/j.1528-1157.1998.tb01155.x
    1. Kraus T., Hösl K., Kiess O., Schanze A., Kornhuber J., Forster C. (2007). BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation. J. Neural Transm. 114, 1485–1493. 10.1007/s00702-007-0755-z
    1. Kraus T., Kiess O., Hösl K., Terekhin P., Kornhuber J., Forster C. (2013). CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal–a pilot study. Brain Stimul. 6, 798–804. 10.1016/j.brs.2013.01.011
    1. Kreuzer P. M., Landgrebe M., Resch M., Husser O., Schecklmann M., Geisreiter F., et al. . (2014). Feasibility, safety and efficacy of transcutaneous vagus nerve stimulation in chronic tinnitus: an open pilot study. Brain Stimul. 7, 740–747. 10.1016/j.brs.2014.05.003
    1. Kwan P., Brodie M. J. (2000). Early identification of refractory epilepsy. N. Engl. J. Med. 342, 314–319. 10.1056/NEJM200002033420503
    1. Labiner D. M., Ahern G. L. (2007). Vagus nerve stimulation therapy in depression and epilepsy: therapeutic parameter settings. Acta Neurol. Scand. 115, 23–33. 10.1111/j.1600-0404.2006.00732.x
    1. Laqua R., Leutzow B., Wendt M., Usichenko T. (2014). Transcutaneous vagal nerve stimulation may elicit anti- and pro-nociceptive effects under experimentally-induced pain–a crossover placebo-controlled investigation. Auton. Neurosci. Basic Clin. 185, 120–122. 10.1016/j.autneu.2014.07.008
    1. Lehtimäki J., Hyvärinen P., Ylikoski M., Bergholm M., Mäkelä J. P., Aarnisalo A., et al. . (2013). Transcutaneous vagus nerve stimulation in tinnitus: a pilot study. Acta Oto-Laryngol. 133, 378–382. 10.3109/00016489.2012.750736
    1. Lerman I., Hauger R., Sorkin L., Proudfoot J., Davis B., Huang A., et al. . (2016). Noninvasive Transcutaneous vagus nerve stimulation decreases whole blood culture-derived cytokines and chemokines: a randomized, blinded, healthy control pilot trial. Neuromodulation 19, 283–290. 10.1111/ner.12398
    1. Liu A., Rong P., Gong L., Song L., Wang X., Li L., et al. . (2018). Efficacy and safety of treatment with transcutaneous vagus nerve stimulation in 17 patients with refractory epilepsy evaluated by electroencephalogram, seizure frequency, and quality of life. Med. Sci. Monit. 24, 8439–8448. 10.12659/MSM.910689
    1. Mahadi K., Lall V., Deuchars S., Deuchars J. (2019). Cardiovascular autonomic effects of transcutaneous auricular nerve stimulation via the tragus in the rat involve spinal cervical sensory afferent pathways. Brain Stimul. 12, 1151–1158. 10.1016/j.brs.2019.05.002
    1. Manta S., Dong J., Debonnel G., Blier P. (2009). Enhancement of the function of rat serotonin and norepinephrine neurons by sustained vagus nerve stimulation. J. Psychiatry Neurosci. 34, 272–280.
    1. Marzec M., Edwards J., Sagher O., Fromes G., Malow B. A. (2003). Effects of vagus nerve stimulation on sleep-related breathing in epilepsy patients. Epilepsia 44, 930–935. 10.1046/j.1528-1157.2003.56202.x
    1. Mayberg H. S. (1997). Limbic-cortical dysregulation: a proposed model of depression. J. Neuropsychiatr. Clin. Neurosci. 9, 471–481. 10.1176/jnp.9.3.471
    1. Mayberg H. S., Brannan S. K., Tekell J. L., Silva J. A., Mahurin R. K., McGinnis S., et al. . (2000). Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol. Psychiatry 48, 830–843. 10.1016/S0006-3223(00)01036-2
    1. Mei Z., Yang S., Cai S., Lei H., Zhou C., Guo Y., et al. (2014). Treatment of tinnitus with electrical stimulation on acupoint in the distribution area of ear vagus nerve combining with sound masking: randomized controlled trial. World J. Acupunct. Moxibust. 24, 30–35. 10.1016/S1003-5257(14)60022-2
    1. Mertens A., Raedt R., Gadeyne S., Carrette E., Boon P., Vonck K. (2018). Recent advances in devices for vagus nerve stimulation. Expert Rev. Med. Devices 15, 527–539. 10.1080/17434440.2018.1507732
    1. Mohr P., Rodriguez M., Slavíčková A., Hanka J. (2011). The application of vagus nerve stimulation and deep brain stimulation in depression. Neuropsychobiology 64, 170–181. 10.1159/000325225
    1. Mourdoukoutas A. P., Truong D. Q., Adair D. K., Simon B. J., Bikson M. (2018). High-resolution multi-scale computational model for non-invasive cervical vagus nerve stimulation. Neuromodulation 21, 261–268. 10.1111/ner.12706
    1. Müller H. H. O., Moeller S., Lücke C., Lam A. P., Braun N., Philipsen A. (2018). Vagus nerve stimulation (VNS) and other augmentation strategies for therapy-resistant depression (TRD): review of the evidence and clinical advice for use. Front. Neurosci. 12:239. 10.3389/fnins.2018.00239
    1. Multon S., Schoenen J. (2005). Pain control by vagus nerve stimulation: from animal to man…and back. Acta Neurol. Belg. 105, 62–67.
    1. Napadow V., Edwards R. R., Cahalan C. M., Mensing G., Greenbaum S., Valovska A., et al. . (2012). Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation. Pain Med. 13, 777–789. 10.1111/j.1526-4637.2012.01385.x
    1. Nemeroff C. B., Mayberg H. S., Krahl S. E., McNamara J., Frazer A., Henry T. R., et al. . (2006). VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology 31, 1345–1355. 10.1038/sj.npp.1301190
    1. Nesbitt A. D., Marin J. C. A., Tompkins E., Ruttledge M. H., Goadsby P. J. (2015). Initial use of a novel noninvasive vagus nerve stimulator for cluster headache treatment. Neurology 84, 1249–1253. 10.1212/WNL.0000000000001394
    1. Peuker E. T., Filler T. J. (2002). The nerve supply of the human auricle. Clin. Anat. 15, 35–37. 10.1002/ca.1089
    1. Polak T., Markulin F., Ehlis A.-C., Langer J. B. M., Ringel T. M., Fallgatter A. J. (2009). Far field potentials from brain stem after transcutaneous vagus nerve stimulation: optimization of stimulation and recording parameters. J. Neural Transm. 116, 1237–1242. 10.1007/s00702-009-0282-1
    1. Randich A., Gebhart G. (1992). Vagal afferent modulation of nociception. Brain. Res. Rev. 17, 77–99. 10.1016/0165-0173(92)90009-B
    1. Redgrave J., Day D., Leung H., Laud P. J., Ali A., Lindert R., et al. . (2018). Safety and tolerability of transcutaneous vagus nerve stimulation in humans; a systematic review. Brain Stimul. 11, 1225–1238. 10.1016/j.brs.2018.08.010
    1. Rong P., Liu A., Zhang J., Wang Y., Yang A., Li L., et al. . (2014). An alternative therapy for drug-resistant epilepsy: transcutaneous auricular vagus nerve stimulation. Chin. Med. J. 127, 300–304. 10.3760/cma.j.issn.0366-6999.20131511
    1. Rong P., Liu J., Wang L., Liu R., Fang J., Zhao J., et al. . (2016). Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: a nonrandomized controlled pilot study. J. Affect. Disord. 195, 172–179. 10.1016/j.jad.2016.02.031
    1. Rong P. J., Fang J. L., Wang L. P., Meng H., Liu J., ge Ma Y., et al. . (2012). Transcutaneous vagus nerve stimulation for the treatment of depression: a study protocol for a double blinded randomized clinical trial. BMC Complement. Altern. Med. 12:255. 10.1186/1472-6882-12-255
    1. Safi S., Ellrich J., Neuhuber W. (2016). Myelinated axons in the auricular branch of the human vagus nerve. Anat. Rec. 299, 1184–1191. 10.1002/ar.23391
    1. Schulz-Stübner S., Kehl F. (2011). Treatment of persistent hiccups with transcutaneous phrenic and vagal nerve stimulation. Intens. Care Med. 37, 1048–1049. 10.1007/s00134-011-2150-3
    1. Seiden D., Corbett S. A., Lachman E. (2013). Lachman's Case Studies in Anatomy. Oxford: Oxford University Press.
    1. Sellaro R., Steenbergen L., Verkuil B., van IJzendoorn M. H., Colzato L. S. (2015a). Transcutaneous vagus nerve stimulation (tVNS) does not increase prosocial behavior in cyberball. Front. Psychol. 6:499 10.3389/fpsyg.2015.00499
    1. Sellaro R., Van Leusden J. W. R., Tona K.-D., Verkuil B., Nieuwenhuis S., Colzato L. S. (2015b). Transcutaneous vagus nerve stimulation enhances post-error slowing. J. Cogn. Neurosci. 27, 2126–2132. 10.1162/jocn_a_00851
    1. Shiozawa P., da Silva M. E., de Carvalho T. C., Cordeiro Q., Brunoni A. R., Fregni F. (2014). Transcutaneous vagus and trigeminal nerve stimulation for neuropsychiatric disorders: a systematic review. Arquiv. Neuro Psiquiatr. 72, 542–547. 10.1590/0004-282X20140061
    1. Silberstein S. D., Calhoun A. H., Lipton R. B., Grosberg B. M., Cady R. K., Dorlas S., et al. . (2016a). Chronic migraine headache prevention with noninvasive vagus nerve stimulation: the EVENT study. Neurology 87, 529–538. 10.1212/WNL.0000000000002918
    1. Silberstein S. D., Mechtler L. L., Kudrow D. B., Calhoun A. H., McClure C., Saper J. R., et al. . (2016b). Non-invasive vagus nerve stimulation for the acute treatment of cluster headache: findings from the randomized, double-blind, Sham-controlled ACT1 study. Headache 56, 1317–1332. 10.1111/head.12896
    1. Standring S. (2015). Gray's Anatomy: The Anatomical Basis of Clinical Practice. Philadelphia, PA: Elsevier Limited.
    1. Stavrakis S., Humphrey M. B., Scherlag B. J., Hu Y., Jackman W. M., Nakagawa H., et al. . (2015). Low-level transcutaneous electrical vagus nerve stimulation suppresses atrial fibrillation. J. Am. Coll. Cardiol. 65, 867–875. 10.1016/j.jacc.2014.12.026
    1. Steenbergen L., Sellaro R., Stock A.-K., Verkuil B., Beste C., Colzato L. S. (2015). Transcutaneous vagus nerve stimulation (tVNS) enhances response selection during action cascading processes. Eur. Neuropsychopharmacol. 25, 773–778. 10.1016/j.euroneuro.2015.03.015
    1. Stefan H., Kreiselmeyer G., Kerling F., Kurzbuch K., Rauch C., Heers M., et al. . (2012). Transcutaneous vagus nerve stimulation (t-VNS) in pharmacoresistant epilepsies: a proof of concept trial. Epilepsia 53, e115–e118. 10.1111/j.1528-1167.2012.03492.x
    1. Straube A., Ellrich J., Eren O., Blum B., Ruscheweyh R. (2015). Treatment of chronic migraine with transcutaneous stimulation of the auricular branch of the vagal nerve (auricular t-VNS): a randomized, monocentric clinical triial. J. Headache Pain 16:543. 10.1186/s10194-015-0543-3
    1. Tekdemir I., Aslan A., Elhan A. (1998). A clinico-anatomic study of the auricular branch of the vagus nerve and Arnold's ear-cough reflex. Surg. Radiol. Anat. 20, 253–257. 10.1007/s00276-998-0253-5
    1. Trevizol A. P., Shiozawa P., Taiar I., Soares A., Gomes J. S., Barros M. D., et al. (2016). Transcutaneous vagus nerve stimulation (taVNS) for major depressive disorder: an open label proof-of-concept trial. Brain Stimul. 9, 453–454. 10.1016/j.brs.2016.02.001
    1. Van Leusden J. W. R., Sellaro R., Colzato L. S. (2015). Transcutaneous vagal nerve stimulation (tVNS): a new neuromodulation tool in healthy humans? Front. Psychol. 6:102. 10.3389/fpsyg.2015.00102
    1. Ventureyra E. C. G. (2000). Transcutaneous vagus nerve stimulation for partial onset seizure therapy. Childs Nerv. Syst. 16, 101–102. 10.1007/s003810050021
    1. Vonck K., De Herdt V., Boon P. (2009). Vagal nerve stimulation-a 15-year survey of an established treatment modality in epilepsy surgery. Adv. Tech. Stand Neurosurg. 34, 111–146. 10.1007/978-3-211-78741-0_5
    1. Walker B. R., Easton A., Gale K. (1999). Regulation of limbic motor seizures by GABA and glutamate transmission in nucleus tractus solitarius. Epilepsia 40, 1051–1057. 10.1111/j.1528-1157.1999.tb00818.x
    1. Weise D., Adamidis M., Pizzolato F., Rumpf J.-J., Fricke C., Classen J. (2015). Assessment of brainstem function with auricular branch of vagus nerve stimulation in Parkinson's disease. PLoS ONE 10:e0120786. 10.1371/journal.pone.0120786
    1. Wexler A. (2015). A pragmatic analysis of the regulation of consumer transcranial direct current stimulation (TDCS) devices in the United States: Table 1. J. Law Biosci. 2:lsv039 10.1093/jlb/lsv039
    1. Yakunina N., Kim S. S., Nam E.-C. (2018). BOLD fMRI effects of transcutaneous vagus nerve stimulation in patients with chronic tinnitus. PLoS ONE 13:e0207281. 10.1371/journal.pone.0207281
    1. Yu Y., Yang Y., Wang L., Fang J., Chen Y., He J., et al. . (2017). Transcutaneous auricular vagus nerve stimulation in disorders of consciousness monitored by fMRI: The first case report. Brain Stimul. 10, 328–330. 10.1016/j.brs.2016.12.004
    1. Yu Z. J., Weller R. A., Sandidge K., Weller E. B. (2008). Vagus nerve stimulation: can it be used in adolescents or children with treatment-resistant depression? Curr. Psychiatry Rep. 10, 116–122. 10.1007/s11920-008-0021-6
    1. Yuan H., Silberstein S. D. (2016a). Vagus nerve and vagus nerve stimulation, a comprehensive review: part I. Headache 56, 71–78. 10.1111/head.12647
    1. Yuan H., Silberstein S. D. (2016b). Vagus nerve and vagus nerve stimulation, a comprehensive review: part II. Headache 56, 259–266. 10.1111/head.12650
    1. Zhao B., Li L., Jiao Y., Luo M., Xu K., Hong Y., et al. . (2019). Transcutaneous auricular vagus nerve stimulation in treating post-stroke insomnia monitored by resting-state fMRI: The first case report. Brain Stimul. 12, 824–826. 10.1016/j.brs.2019.02.016

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever