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Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature

      Abstract

      Objectives

      After 20 years of development, there is confusion in the nomenclature of transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN). We performed a systematic review of transcutaneous stimulation of ABVN in nomenclature.

      Materials and Methods

      A systematic search of the literature was carried out, using the bibliographic search engine PubMed. The search covered articles published up until June 11, 2020. We recorded the full nomenclature and abbreviated nomenclature same or similar to transcutaneous stimulation of ABVN in the selected eligible studies, as well as the time and author information of this nomenclature.

      Results

      From 261 studies, 67 full nomenclatures and 27 abbreviated nomenclatures were finally screened out, transcutaneous vagus nerve stimulation and tVNS are the most common nomenclature, accounting for 38.38% and 42.06%, respectively. In a total of 97 combinations of full nomenclatures and abbreviations, the most commonly used nomenclature for the combination of transcutaneous vagus nerve stimulation and tVNS, accounting for 30.28%. Interestingly, the combination of full nomenclatures and abbreviations is not always a one-to-one relationship, there are ten abbreviated nomenclatures corresponding to transcutaneous vagus nerve stimulation, and five full nomenclatures corresponding to tVNS. In addition, based on the analysis of the usage habits of nomenclature in 21 teams, it is found that only three teams have fixed habits, while other different teams or the same team do not always use the same nomenclature in their paper.

      Conclusions

      The phenomenon of confusion in the nomenclature of transcutaneous stimulation of ABVN is obvious and shows a trend of diversity. The nomenclature of transcutaneous stimulation of ABVN needs to become more standardized in the future.

      Keywords

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      References

        • He W.
        • Wang X.
        • Shi H.
        • et al.
        Auricular acupuncture and vagal regulation.
        Evid Based Complement Alternat Med. 2012; 2012: 786839
        • Howland R.H.
        Vagus nerve stimulation.
        Curr Behav Neurosci Rep. 2014; 1: 64-73
        • Ventureyra E.C.
        Transcutaneous vagus nerve stimulation for partial onset seizure therapy. A new concept.
        Childs Nerv Syst. 2000; 16: 101-102
        • Zorzela L.
        • Loke Y.K.
        • Ioannidis J.P.
        • et al.
        PRISMA harms checklist: improving harms reporting in systematic reviews.
        BMJ. 2016; 352: i157https://doi.org/10.1136/bmj.i157
        • Yap J.Y.Y.
        • Keatch C.
        • Lambert E.
        • Woods W.
        • Stoddart P.R.
        • Kameneva T.
        Critical review of transcutaneous vagus nerve stimulation: challenges for translation to clinical practice.
        Front Neurosci. 2020; 14: 284
        • Mertens A.
        • Naert L.
        • Miatton M.
        • et al.
        Transcutaneous vagus nerve stimulation does not affect verbal memory performance in healthy volunteers.
        Front Psychol. 2020; 11: 551
        • Maraver M.J.
        • Steenbergen L.
        • Hossein R.
        • et al.
        Transcutaneous vagus nerve stimulation modulates attentional resource deployment towards social cues.
        Neuropsychologia. 2020; 143: 107465
        • Hakon J.
        • Moghiseh M.
        • Poulsen I.
        • CML Øland
        • Hansen C.P.
        • Sabers A.
        Transcutaneous vagus nerve stimulation in patients with severe traumatic brain injury: a feasibility trial.
        Neuromodulation. 2020; 23: 859-864
        • Colzato L.
        • Beste C.
        A literature review on the neurophysiological underpinnings and cognitive effects of transcutaneous vagus nerve stimulation: challenges and future directions.
        J Neurophysiol. 2020; 123: 1739-1755
        • Burger A.M.
        • D'Agostini M.
        • Verkuil B.
        • Van Diest I.
        Moving beyond belief: a narrative review of potential biomarkers for transcutaneous vagus nerve stimulation.
        Psychophysiology. 2020; 57: e13571
        • Wu K.
        • Wang Z.
        • Zhang Y.
        • Yao J.
        • Zhang Z.
        Transcutaneous vagus nerve stimulation for the treatment of drug-resistant epilepsy: a meta-analysis and systematic review.
        ANZ J Surg. 2020; 90: 467-471
        • Szeska C.
        • Richter J.
        • Wendt J.
        • Weymar M.
        • Hamm A.O.
        Promoting long-term inhibition of human fear responses by non-invasive transcutaneous vagus nerve stimulation during extinction training.
        Sci Rep. 2020; 10: 1529
        • Koenig J.
        • Parzer P.
        • Haigis N.
        • et al.
        Effects of acute transcutaneous vagus nerve stimulation on emotion recognition in adolescent depression.
        Psychol Med. 2019; 1–10https://doi.org/10.1017/S0033291719003490
        • Butt M.F.
        • Albusoda A.
        • Farmer A.D.
        • Aziz Q.
        The anatomical basis for transcutaneous auricular vagus nerve stimulation.
        J Anat. 2020; 236: 588-611
        • Steenbergen L.
        • Colzato L.S.
        • Maraver M.J.
        Vagal signaling and the somatic marker hypothesis: the effect of transcutaneous vagal nerve stimulation on delay discounting is modulated by positive mood.
        Int J Psychophysiol. 2020; 148: 84-92
        • Ellrich J.
        Transcutaneous auricular vagus nerve stimulation.
        J Clin Neurophysiol. 2019; 36: 437-442
        • Borges U.
        • Laborde S.
        • Raab M.
        Influence of transcutaneous vagus nerve stimulation on cardiac vagal activity: not different from sham stimulation and no effect of stimulation intensity.
        PLoS One. 2019; 14: e0223848
        • Sternberg Z.
        • Schaller B.
        Central noradrenergic agonists in the treatment of ischemic stroke—an overview.
        Transl Stroke Res. 2020; 11: 165-184
        • von Wrede R.
        • Moskau-Hartmann S.
        • Rüber T.
        • Helmstaedter C.
        • Surges R.
        Sustained seizure freedom with transcutaneous vagal nerve stimulation in drug-resistant epilepsy caused by subcortical band heterotopias.
        Seizure. 2019; 70: 25-26
        • Paccione C.E.
        • Jacobsen H.B.
        Motivational non-directive resonance breathing as a treatment for chronic widespread pain.
        Front Psychol. 2019; 10: 1207
        • Finisguerra A.
        • Crescentini C.
        • Urgesi C.
        Transcutaneous vagus nerve stimulation affects implicit spiritual self-representations.
        Neuroscience. 2019; 412: 144-159
        • Burger A.M.
        • Van Diest I.
        • Van der Does W.
        • et al.
        The effect of transcutaneous vagus nerve stimulation on fear generalization and subsequent fear extinction.
        Neurobiol Learn Mem. 2019; 161: 192-201
        • Tobaldini E.
        • Toschi-Dias E.
        • Appratto de Souza L.
        • Rabello Casali K.
        • Vicenzi M.
        • Sandrone G.
        Cardiac and peripheral autonomic responses to orthostatic stress during transcutaneous vagus nerve stimulation in healthy subjects.
        J Clin Med. 2019; 8: 496
        • Bialer M.
        • Johannessen S.I.
        • Koepp M.J.
        • et al.
        A summary of data presented at the XIV conference on new antiepileptic drug and devices (EILAT XIV).
        Epilepsy Res. 2019; 153: 66-67
        • Keute M.
        • Boehrer L.
        • Ruhnau P.
        • Heinze H.J.
        • Zaehle T.
        Transcutaneous vagus nerve stimulation (tVNS) and the dynamics of visual bistable perception.
        Front Neurosci. 2019; 13: 227
        • Hamer H.M.
        • Bauer S.
        Lessons learned from transcutaneous vagus nerve stimulation (tVNS).
        Epilepsy Res. 2019; 153: 83-84
        • Costa B.
        • Ferreira I.
        • Trevizol A.
        • Thibaut A.
        • Fregni F.
        Emerging targets and uses of neuromodulation for pain.
        Expert Rev Neurother. 2019; 19: 109-118
        • Warren C.M.
        • Tona K.D.
        • Ouwerkerk L.
        • et al.
        The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential.
        Brain Stimul. 2019; 12: 635-642
        • Hong G.S.
        • Pintea B.
        • Lingohr P.
        • et al.
        Effect of transcutaneous vagus nerve stimulation on muscle activity in the gastrointestinal tract (transVaGa): a prospective clinical trial.
        Int J Colorectal Dis. 2019; 34: 417-422
        • Yakunina N.
        • Kim S.S.
        • Nam E.C.
        BOLD fMRI effects of transcutaneous vagus nerve stimulation in patients with chronic tinnitus.
        PLoS One. 2018; 13: e0207281
        • Liu A.
        • Rong P.
        • Gong L.
        • et al.
        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. 2018; 24: 8439-8448
        • Hong G.S.
        • Zillekens A.
        • Schneiker B.
        • et al.
        Non-invasive transcutaneous auricular vagus nerve stimulation prevents postoperative ileus and endotoxemia in mice.
        Neurogastroenterol Motil. 2019; 31: e13501
        • Rangon C.M.
        Reconsidering sham in transcutaneous vagus nerve stimulation studies.
        Clin Neurophysiol. 2018; 129: 2501-2502
        • Keute M.
        • Ruhnau P.
        • Zaehle T.
        Reply to "Reconsidering sham in transcutaneous vagus nerve stimulation studies".
        Clin Neurophysiol. 2018; 129: 2503-2504
        • Redgrave J.
        • Day D.
        • Leung H.
        • et al.
        Safety and tolerability of transcutaneous vagus nerve stimulation in humans: a systematic review.
        Brain Stimul. 2018; 11: 1225-1238
        • Suk W.C.
        • Kim S.J.
        • Chang D.S.
        • Lee H.Y.
        Characteristics of stimulus intensity in transcutaneous vagus nerve stimulation for chronic tinnitus.
        J Int Adv Otol. 2018; 14: 267-272
        • Mertens A.
        • Raedt R.
        • Gadeyne S.
        • Carrette E.
        • Boon P.
        • Vonck K.
        Recent advances in devices for vagus nerve stimulation.
        Expert Rev Med Devices. 2018; 15: 527-539
        • Fischer R.
        • Ventura-Bort C.
        • Hamm A.
        • Weymar M.
        Transcutaneous vagus nerve stimulation (tVNS) enhances conflict-triggered adjustment of cognitive control.
        Cogn Affect Behav Neurosci. 2018; 18: 680-693
        • Jongkees B.J.
        • Immink M.A.
        • Finisguerra A.
        • Colzato L.S.
        Transcutaneous vagus nerve stimulation (tVNS) enhances response selection during sequential action.
        Front Psychol. 2018; 9: 1159
        • Keute M.
        • Ruhnau P.
        • Heinze H.J.
        • Zaehle T.
        Behavioral and electrophysiological evidence for GABAergic modulation through transcutaneous vagus nerve stimulation.
        Clin Neurophysiol. 2018; 129: 1789-1795
        • Ventura-Bort C.
        • Wirkner J.
        • Genheimer H.
        • Wendt J.
        • Hamm A.O.
        • Weymar M.
        Effects of transcutaneous vagus nerve stimulation (tVNS) on the P300 and alpha-amylase level: a pilot study.
        Front Hum Neurosci. 2018; 12: 202
        • Kwon C.S.
        • Ripa V.
        • Al-Awar O.
        • Panov F.
        • Ghatan S.
        • Jetté N.
        Epilepsy and neuromodulation-randomized controlled trials.
        Brain Sci. 2018; 8: 69
        • Burger A.M.
        • Verkuil B.
        Transcutaneous nerve stimulation via the tragus: are we really stimulating the vagus nerve?.
        Brain Stimul. 2018; 11: 945-946
        • Boon P.
        • De Cock E.
        • Mertens A.
        • Trinka E.
        Neurostimulation for drug-resistant epilepsy: a systematic review of clinical evidence for efficacy, safety, contraindications and predictors for response.
        Curr Opin Neurol. 2018; 31: 198-210
        • Tu Y.
        • Fang J.
        • Cao J.
        • et al.
        A distinct biomarker of continuous transcutaneous vagus nerve stimulation treatment in major depressive disorder.
        Brain Stimul. 2018; 11: 501-508
        • Mercante B.
        • Deriu F.
        • Rangon C.M.
        Auricular neuromodulation: the emerging concept beyond the stimulation of vagus and trigeminal nerves.
        Medicines. 2018; 5: 10
        • Colzato L.S.
        • Ritter S.M.
        • Steenbergen L.
        Transcutaneous vagus nerve stimulation (tVNS) enhances divergent thinking.
        Neuropsychologia. 2018; 111: 72-76
        • Wang Z.
        • Fang J.
        • Liu J.
        • et al.
        Frequency-dependent functional connectivity of the nucleus accumbens during continuous transcutaneous vagus nerve stimulation in major depressive disorder.
        J Psychiatr Res. 2018; 102: 123-131
        • Genheimer H.
        • Andreatta M.
        • Asan E.
        • Pauli P.
        Reinstatement of contextual conditioned anxiety in virtual reality and the effects of transcutaneous vagus nerve stimulation in humans.
        Sci Rep. 2017; 7: 17886
        • Deuchars S.A.
        • Lall V.K.
        • Clancy J.
        • et al.
        Mechanisms underpinning sympathetic nervous activity and its modulation using transcutaneous vagus nerve stimulation.
        Exp Physiol. 2018; 103: 326-331
        • Sellaro R.
        • de Gelder B.
        • Finisguerra A.
        • Colzato L.S.
        Transcutaneous vagus nerve stimulation (tVNS) enhances recognition of emotions in faces but not bodies.
        Cortex. 2018; 99: 213-223
        • Colzato L.S.
        • Wolters G.
        • Peifer C.
        Transcutaneous vagus nerve stimulation (tVNS) modulates flow experience.
        Exp Brain Res. 2018; 236: 253-257
        • Göbel C.H.
        • Tronnier V.M.
        • Münte T.F.
        Brain stimulation in obesity.
        Int J Obes. 2017; 41: 1721-1727
        • Burger A.M.
        • Verkuil B.
        • Fenlon H.
        • et al.
        Mixed evidence for the potential of non-invasive transcutaneous vagal nerve stimulation to improve the extinction and retention of fear.
        Behav Res Ther. 2017; 97: 64-74
        • Nicholson W.C.
        • Kempf M.C.
        • Moneyham L.
        • Vance D.E.
        The potential role of vagus-nerve stimulation in the treatment of HIV-associated depression: a review of literature.
        Neuropsychiatr Dis Treat. 2017; 13: 1677-1689
        • Antonino D.
        • Teixeira A.L.
        • Maia-Lopes P.M.
        • et al.
        Non-invasive vagus nerve stimulation acutely improves spontaneous cardiac baroreflex sensitivity in healthy young men: a randomized placebo-controlled trial.
        Brain Stimul. 2017; 10: 875-881
        • Colzato L.S.
        • Sellaro R.
        • Beste C.
        Darwin revisited: the vagus nerve is a causal element in controlling recognition of other's emotions.
        Cortex. 2017; 92: 95-102
        • Jin Y.
        • Kong J.
        Transcutaneous vagus nerve stimulation: a promising method for treatment of autism spectrum disorders.
        Front Neurosci. 2017; 10: 609
        • Fang J.
        • Egorova N.
        • Rong P.
        • et al.
        Early cortical biomarkers of longitudinal transcutaneous vagus nerve stimulation treatment success in depression.
        Neuroimage Clin. 2016; 14: 105-111
        • Cimpianu C.L.
        • Strube W.
        • Falkai P.
        • Palm U.
        • Hasan A.
        Vagus nerve stimulation in psychiatry: a systematic review of the available evidence.
        J Neural Transm. 2017; 124: 145-158
        • Schulze-Bonhage A.
        Brain stimulation as a neuromodulatory epilepsy therapy.
        Seizure. 2017; 44: 169-175
        • Anfinogenova Y.
        Vagus nerve stimulation: invasive or noninvasive?.
        Anatol J Cardiol. 2016; 16: 811-812
        • Liu J.
        • Fang J.
        • Wang Z.
        • et al.
        Transcutaneous vagus nerve stimulation modulates amygdala functional connectivity in patients with depression.
        J Affect Disord. 2016; 205: 319-326
        • Beste C.
        • Steenbergen L.
        • Sellaro R.
        • et al.
        Effects of concomitant stimulation of the GABAergic and norepinephrine system on inhibitory control - a study using transcutaneous vagus nerve stimulation.
        Brain Stimul. 2016; 9: 811-818
        • Murray A.R.
        • Atkinson L.
        • Mahadi M.K.
        • Deuchars S.A.
        • Deuchars J.
        The strange case of the ear and the heart: the auricular vagus nerve and its influence on cardiac control.
        Auton Neurosci. 2016; 199: 48-53
        • Burger A.M.
        • Verkuil B.
        • Van Diest I.
        • Van der Does W.
        • Thayer J.F.
        • Brosschot J.F.
        The effects of transcutaneous vagus nerve stimulation on conditioned fear extinction in humans.
        Neurobiol Learn Mem. 2016; 132: 49-56
        • Bonaz B.
        • Sinniger V.
        • Pellissier S.
        Anti-inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation.
        J Physiol. 2016; 594: 5781-5790
        • Cha W.W.
        • Song K.
        • Lee H.Y.
        Persistent geotropic direction-changing positional nystagmus treated with transcutaneous vagus nerve stimulation.
        Brain Stimul. 2016; 9: 469-470
        • Carreno F.R.
        • Frazer A.
        The allure of transcutaneous vagus nerve stimulation as a novel therapeutic modality.
        Biol Psychiatry. 2016; 79: 260-261
        • Bauer S.
        • Baier H.
        • Baumgartner C.
        • et al.
        Transcutaneous vagus nerve stimulation (tVNS) for treatment of drug-resistant epilepsy: a randomized, double-blind clinical trial (cMPsE02).
        Brain Stimul. 2016; 9: 356-363
        • Shim H.J.
        • Kwak M.Y.
        • An Y.H.
        • Kim D.H.
        • Kim Y.J.
        • Kim H.J.
        Feasibility and safety of transcutaneous vagus nerve stimulation paired with notched music therapy for the treatment of chronic tinnitus.
        J Audiol Otol. 2015; 19: 159-167
        • Trevizol A.P.
        • Taiar I.
        • Barros M.D.
        • Liquidatto B.
        • Cordeiro Q.
        • Shiozawa P.
        Transcutaneous vagus nerve stimulation (tVNS) protocol for the treatment of major depressive disorder: a case study assessing the auricular branch of the vagus nerve.
        Epilepsy Behav. 2015; 53: 166-167
        • Guerrini R.
        • Duchowny M.
        • Jayakar P.
        • et al.
        Diagnostic methods and treatment options for focal cortical dysplasia.
        Epilepsia. 2015; 56: 1669-1686
        • Trevizol A.
        • Barros M.D.
        • Liquidato B.
        • Cordeiro Q.
        • Shiozawa P.
        Vagus nerve stimulation in neuropsychiatry: targeting anatomy-based stimulation sites.
        Epilepsy Behav. 2015; 51: 18
        • Sellaro R.
        • van Leusden J.W.
        • Tona K.D.
        • Verkuil B.
        • Nieuwenhuis S.
        • Colzato L.S.
        Transcutaneous vagus nerve stimulation enhances post-error slowing.
        J Cogn Neurosci. 2015; 27: 2126-2132
        • Hyvärinen P.
        • Yrttiaho S.
        • Lehtimäki J.
        • et al.
        Transcutaneous vagus nerve stimulation modulates tinnitus-related beta- and gamma-band activity.
        Ear Hear. 2015; 36: e76-e85
        • Sellaro R.
        • Steenbergen L.
        • Verkuil B.
        • van Ijzendoorn M.H.
        • Colzato L.S.
        Transcutaneous vagus nerve stimulation (tVNS) does not increase prosocial behavior in cyberball.
        Front Psychol. 2015; 6: 499
        • Fang J.
        • Rong P.
        • Hong Y.
        • et al.
        Transcutaneous vagus nerve stimulation modulates default mode network in major depressive disorder.
        Biol Psychiatry. 2016; 79: 266-273
        • Steenbergen L.
        • Sellaro R.
        • Stock A.K.
        • Verkuil B.
        • Beste C.
        • Colzato L.S.
        Transcutaneous vagus nerve stimulation (tVNS) enhances response selection during action cascading processes.
        Eur Neuropsychopharmacol. 2015; 25: 773-778
        • Jacobs H.I.
        • Riphagen J.M.
        • Razat C.M.
        • Wiese S.
        • Sack A.T.
        Transcutaneous vagus nerve stimulation boosts associative memory in older individuals.
        Neurobiol Aging. 2015; 36: 1860-1867
        • Ben-Menachem E.
        • Revesz D.
        • Simon B.J.
        • Silberstein S.
        Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability.
        Eur J Neurol. 2015; 22: 1260-1268
        • Capone F.
        • Assenza G.
        • Di Pino G.
        • et al.
        The effect of transcutaneous vagus nerve stimulation on cortical excitability.
        J Neural Transm. 2015; 122: 679-685
        • Clancy J.A.
        • Mary D.A.
        • Witte K.K.
        • Greenwood J.P.
        • Deuchars S.A.
        • Deuchars J.
        Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity.
        Brain Stimul. 2014; 7: 871-877
        • Shiozawa P.
        • Silva M.E.
        • Carvalho T.C.
        • Cordeiro Q.
        • Brunoni A.R.
        • Fregni F.
        Transcutaneous vagus and trigeminal nerve stimulation for neuropsychiatric disorders: a systematic review.
        Arq Neuropsiquiatr. 2014; 72: 542-547
        • Kraus T.
        • Kiess O.
        • Hösl K.
        • Terekhin P.
        • Kornhuber J.
        • Forster C.
        CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal - a pilot study.
        Brain Stimul. 2013; 6: 798-804
        • Rong P.J.
        • Fang J.L.
        • Wang L.P.
        • et al.
        Transcutaneous vagus nerve stimulation for the treatment of depression: a study protocol for a double blinded randomized clinical trial.
        BMC Complement Altern Med. 2012; 12: 255
        • Lehtimäki J.
        • Hyvärinen P.
        • Ylikoski M.
        • et al.
        Transcutaneous vagus nerve stimulation in tinnitus: a pilot study.
        Acta Otolaryngol. 2013; 133: 378-382
        • Hein E.
        • Nowak M.
        • Kiess O.
        • et al.
        Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study.
        J Neural Transm. 2013; 120: 821-827
        • Kreuzer P.M.
        • Landgrebe M.
        • Husser O.
        • et al.
        Transcutaneous vagus nerve stimulation: retrospective assessment of cardiac safety in a pilot study.
        Front Psychiatry. 2012; 3: 70
        • Dietrich S.
        • Smith J.
        • Scherzinger C.
        • et al.
        A novel transcutaneous vagus nerve stimulation leads to brainstem and cerebral activations measured by functional MRI.
        Biomed Tech. 2008; 53: 104-111
        • Kühnel A.
        • Teckentrup V.
        • Neuser M.P.
        • et al.
        Stimulation of the vagus nerve reduces learning in a go/no-go reinforcement learning task.
        Eur Neuropsychopharmacol. 2020; 35: 17-29
        • Badran B.W.
        • Jenkins D.D.
        • Cook D.
        • et al.
        Transcutaneous auricular vagus nerve stimulation-paired rehabilitation for oromotor feeding problems in newborns: an open-label pilot study.
        Front Hum Neurosci. 2020; 14: 77
        • Zhao B.
        • Bi Y.
        • Li L.
        • et al.
        The instant spontaneous neuronal activity modulation of transcutaneous auricular vagus nerve stimulation on patients with primary insomnia.
        Front Neurosci. 2020; 14: 205
        • Cook D.N.
        • Thompson S.
        • Stomberg-Firestein S.
        • et al.
        Design and validation of a closed-loop, motor-activated auricular vagus nerve stimulation (MAAVNS) system for neurorehabilitation.
        Brain Stimul. 2020; 13: 800-803
        • Liu C.H.
        • Yang M.H.
        • Zhang G.Z.
        • et al.
        Neural networks and the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation in depression.
        J Neuroinflammation. 2020; 17: 54
        • Bucksot J.E.
        • Morales Castelan K.
        • Skipton S.K.
        • Hays S.A.
        Parametric characterization of the rat Hering-Breuer reflex evoked with implanted and non-invasive vagus nerve stimulation.
        Exp Neurol. 2020; 327: 113220
        • Teckentrup V.
        • Neubert S.
        • Santiago J.C.P.
        • Hallschmid M.
        • Walter M.
        • Kroemer N.B.
        Non-invasive stimulation of vagal afferents reduces gastric frequency.
        Brain Stimul. 2020; 13: 470-473
        • Baig S.S.
        • Falidas K.
        • Laud P.J.
        • et al.
        Transcutaneous auricular vagus nerve stimulation with upper limb repetitive task practice may improve sensory recovery in chronic stroke.
        J Stroke Cerebrovasc Dis. 2019; 28: 104348
        • Ma J.
        • Qiao P.
        • Li Q.
        • et al.
        Vagus nerve stimulation as a promising adjunctive treatment for ischemic stroke.
        Neurochem Int. 2019; 131: 104539
        • Keute M.
        • Demirezen M.
        • Graf A.
        • Mueller N.G.
        • Zaehle T.
        No modulation of pupil size and event-related pupil response by transcutaneous auricular vagus nerve stimulation (taVNS).
        Sci Rep. 2019; 9: 11452
        • Ulgen Y.
        • Buyuksarac B.
        • Tunc B.
        • Solmaz H.
        Extracellular and intracellular fluid shifts on the onset of transcutaneous auricular vagus nerve stimulation.
        Annu Int Conf IEEE Eng Med Biol Soc. 2019; 2019: 6888-6891
        • Rawat J.K.
        • Roy S.
        • Singh M.
        • et al.
        Transcutaneous vagus nerve stimulation regulates the cholinergic anti-inflammatory pathway to counteract 1, 2-dimethylhydrazine induced colon carcinogenesis in albino wistar rats.
        Front Pharmacol. 2019; 10: 353
        • Paleczny B.
        • Seredyński R.
        • Ponikowska B.
        Inspiratory- and expiratory-gated transcutaneous vagus nerve stimulation have different effects on heart rate in healthy subjects: preliminary results.
        Clin Auton Res. 2021; 31: 205-214
        • Zhao B.
        • Li L.
        • Jiao Y.
        • et al.
        Transcutaneous auricular vagus nerve stimulation in treating post-stroke insomnia monitored by resting-state fMRI: the first case report.
        Brain Stimul. 2019; 12: 824-826
        • Sclocco R.
        • Garcia R.G.
        • Kettner N.W.
        • et al.
        The influence of respiration on brainstem and cardiovagal response to auricular vagus nerve stimulation: a multimodal ultrahigh-field (7T) fMRI study.
        Brain Stimul. 2019; 12: 911-921
        • Badran B.W.
        • Yu A.B.
        • Adair D.
        • et al.
        Laboratory administration of transcutaneous auricular vagus nerve stimulation (taVNS): technique, targeting, and considerations.
        J Vis Exp. 2019; 143 (10.3791/58984)
        • Zhang Y.
        • Liu J.
        • Li H.
        • et al.
        Transcutaneous auricular vagus nerve stimulation at 1 Hz modulates locus coeruleus activity and resting state functional connectivity in patients with migraine: an fMRI study.
        Neuroimage Clin. 2019; 24: 101971
        • Wu C.
        • Liu P.
        • Fu H.
        • et al.
        Transcutaneous auricular vagus nerve stimulation in treating major depressive disorder: a systematic review and meta-analysis.
        Medicine. 2018; 97: e13845
        • Badran B.W.
        • Jenkins D.D.
        • DeVries W.H.
        • et al.
        Transcutaneous auricular vagus nerve stimulation (taVNS) for improving oromotor function in newborns.
        Brain Stimul. 2018; 11: 1198-1200
        • Badran B.W.
        • Brown J.C.
        • Dowdle L.T.
        • et al.
        Tragus or cymba conchae? Investigating the anatomical foundation of transcutaneous auricular vagus nerve stimulation (taVNS).
        Brain Stimul. 2018; 11: 947-948
        • Badran B.W.
        • Mithoefer O.J.
        • Summer C.E.
        • et al.
        Short trains of transcutaneous auricular vagus nerve stimulation (taVNS) have parameter-specific effects on heart rate.
        Brain Stimul. 2018; 11: 699-708
        • 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.
        Front Psychiatry. 2018; 9: 20
        • Osoegawa C.
        • Gomes J.S.
        • Grigolon R.B.
        • et al.
        Non-invasive brain stimulation for negative symptoms in schizophrenia: an updated systematic review and meta-analysis.
        Schizophr Res. 2018; 197: 34-44
        • Li S.
        • Sun C.
        • Rong P.
        • et al.
        Auricular vagus nerve stimulation enhances central serotonergic function and inhibits diabetic neuropathy development in Zucker fatty rats.
        Mol Pain. 2018; 14 (1744806918787368)
        • Badran B.W.
        • Dowdle L.T.
        • Mithoefer O.J.
        • 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 Stimul. 2018; 11: 492-500
        • Gancheva S.
        • Bierwagen A.
        • Markgraf D.F.
        • et al.
        Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos ® on parasympathetic tone and hepatic energy metabolism.
        Mol Metab. 2018; 7: 71-79
        • Trevizol A.P.
        • Shiozawa P.
        • Taiar I.
        • et al.
        Transcutaneous vagus nerve stimulation (taVNS) for major depressive disorder: an open label proof-of-concept trial.
        Brain Stimul. 2016; 9: 453-454
        • Rong P.
        • Liu J.
        • Wang L.
        • et al.
        Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: a nonrandomized controlled pilot study.
        J Affect Disord. 2016; 195: 172-179
        • Li S.
        • Zhai X.
        • Rong P.
        • et al.
        Therapeutic effect of vagus nerve stimulation on depressive-like behavior, hyperglycemia and insulin receptor expression in Zucker fatty rats.
        PLoS One. 2014; 9: e112066
        • Li S.
        • Zhai X.
        • Rong P.
        • et al.
        Transcutaneous auricular vagus nerve stimulation triggers melatonin secretion and is antidepressive in Zucker diabetic fatty rats.
        PLoS One. 2014; 9: e111100
        • Huang F.
        • Dong J.
        • Kong J.
        • et al.
        Effect of transcutaneous auricular vagus nerve stimulation on impaired glucose tolerance: a pilot randomized study.
        BMC Complement Altern Med. 2014; 14: 203
        • Li J.
        • Zhang Q.
        • Li S.
        • et al.
        α7nAchR mediates transcutaneous auricular vagus nerve stimulation-induced neuroprotection in a rat model of ischemic stroke by enhancing axonal plasticity.
        Neurosci Lett. 2020; 730: 135031
        • Ma J.
        • Zhang L.
        • He G.
        • Tan X.
        • Jin X.
        • Li C.
        Transcutaneous auricular vagus nerve stimulation regulates expression of growth differentiation factor 11 and activin-like kinase 5 in cerebral ischemia/reperfusion rats.
        J Neurol Sci. 2016; 369: 27-35
        • Bonaz B.
        • Sinniger V.
        • Pellissier S.
        Vagal tone: effects on sensitivity, motility, and inflammation.
        Neurogastroenterol Motil. 2016; 28: 455-462
        • He W.
        • Wang X.Y.
        • Zhou L.
        • et al.
        Transcutaneous auricular vagus nerve stimulation for pediatric epilepsy: study protocol for a randomized controlled trial.
        Trials. 2015; 16: 371
        • Rong P.
        • Liu A.
        • Zhang J.
        • et al.
        Transcutaneous vagus nerve stimulation for refractory epilepsy: a randomized controlled trial.
        Clin Sci. 2014; 2014: CS20130518https://doi.org/10.1042/CS20130518
        • Rong P.
        • Liu A.
        • Zhang J.
        • et al.
        An alternative therapy for drug-resistant epilepsy: transcutaneous auricular vagus nerve stimulation.
        Chin Med J. 2014; 127: 300-304
        • He W.
        • Jing X.H.
        • Zhu B.
        • et al.
        The auriculo-vagal afferent pathway and its role in seizure suppression in rats.
        BMC Neurosci. 2013; 14: 85
        • He W.
        • Jing X.
        • Wang X.
        • et al.
        Transcutaneous auricular vagus nerve stimulation as a complementary therapy for pediatric epilepsy: a pilot trial.
        Epilepsy Behav. 2013; 28: 343-346
        • Zhao Y.X.
        • He W.
        • Jing X.H.
        • et al.
        Transcutaneous auricular vagus nerve stimulation protects endotoxemic rat from lipopolysaccharide-induced inflammation.
        Evid Based Complement Alternat Med. 2012; 2012: 627023
        • Bretherton B.
        • Atkinson L.
        • Murray A.
        • Clancy J.
        • Deuchars S.
        • Deuchars J.
        Effects of transcutaneous vagus nerve stimulation in individuals aged 55 years or above: potential benefits of daily stimulation.
        Aging. 2019; 11: 4836-4857
        • Mahadi K.M.
        • Lall V.K.
        • Deuchars S.A.
        • Deuchars J.
        Cardiovascular autonomic effects of transcutaneous auricular nerve stimulation via the tragus in the rat involve spinal cervical sensory afferent pathways.
        Brain Stimul. 2019; 12: 1151-1158
        • Early S.
        • Stankovic K.M.
        Reversible sensorineural hearing loss associated with off-label use of transcutaneous vagal nerve stimulator.
        Otolaryngol Head Neck Surg. 2018; 159: 802-804
        • Rufener K.S.
        • Geyer U.
        • Janitzky K.
        • Heinze H.J.
        • Zaehle T.
        Modulating auditory selective attention by non-invasive brain stimulation: differential effects of transcutaneous vagal nerve stimulation and transcranial random noise stimulation.
        Eur J Neurosci. 2018; 48: 2301-2309
        • Lamb D.G.
        • Porges E.C.
        • Lewis G.F.
        • Williamson J.B.
        Non-invasive vagal nerve stimulation effects on hyperarousal and autonomic state in patients with posttraumatic stress disorder and history of mild traumatic brain injury: preliminary evidence.
        Front Med. 2017; 4: 124
        • Ylikoski J.
        • Lehtimäki J.
        • Pirvola U.
        • et al.
        Non-invasive vagus nerve stimulation reduces sympathetic preponderance in patients with tinnitus.
        Acta Otolaryngol. 2017; 137: 426-431
        • Van Leusden J.W.
        • Sellaro R.
        • Colzato L.S.
        Transcutaneous vagal nerve stimulation (tVNS): a new neuromodulation tool in healthy humans?.
        Front Psychol. 2015; 6: 102
        • Manning K.E.
        • Beresford-Webb J.A.
        • Aman L.C.S.
        • et al.
        Transcutaneous vagus nerve stimulation (t-VNS): a novel effective treatment for temper outbursts in adults with Prader-Willi syndrome indicated by results from a non-blind study.
        PLoS One. 2019; 14: e0223750
        • De Couck M.
        • Cserjesi R.
        • Caers R.
        • et al.
        Effects of short and prolonged transcutaneous vagus nerve stimulation on heart rate variability in healthy subjects.
        Auton Neurosci. 2017; 203: 88-96
        • Frangos E.
        • Ellrich J.
        • Komisaruk B.R.
        Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: fMRI evidence in humans.
        Brain Stimul. 2015; 8: 624-636
        • Aihua L.
        • Lu S.
        • Liping L.
        • Xiuru W.
        • Hua L.
        • Yuping W.
        A controlled trial of transcutaneous vagus nerve stimulation for the treatment of pharmacoresistant epilepsy.
        Epilepsy Behav. 2014; 39: 105-110
        • Stefan H.
        • Kreiselmeyer G.
        • Kerling F.
        • et al.
        Transcutaneous vagus nerve stimulation (t-VNS) in pharmacoresistant epilepsies: a proof of concept trial.
        Epilepsia. 2012; 53: e115-e118
        • Eichhammer P.
        Potential for transcutaneous vagus nerve stimulation in pain management.
        Pain Manag. 2011; 1: 287-289
        • Kraus T.
        • Hösl K.
        • Kiess O.
        • Schanze A.
        • Kornhuber J.
        • Forster C.
        BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation.
        J Neural Transm. 2007; 114: 1485-1493
        • Verkuil B.
        • Burger A.M.
        Transcutaneous vagus nerve stimulation does not affect attention to fearful faces in high worriers.
        Behav Res Ther. 2019; 113: 25-31
        • Li X.J.
        • Wang L.
        • Wang H.X.
        • et al.
        The effect of transcutaneous auricular vagus nerve stimulation on treatment-resistant depression monitored by resting-state fMRI and MRS: the first case report.
        Brain Stimul. 2019; 12: 377-379
        • Yu Y.T.
        • Yang Y.
        • Wang L.B.
        • et al.
        Transcutaneous auricular vagus nerve stimulation in disorders of consciousness monitored by fMRI: the first case report.
        Brain Stimul. 2017; 10: 328-330
        • Oliveira T.V.H.F.
        • Francisco A.N.
        • Demartini Z.
        • Stebel S.L.
        The role of vagus nerve stimulation in refractory epilepsy.
        Arq Neuropsiquiatr. 2017; 75: 657-666
        • Akdemir B.
        • Benditt D.G.
        Vagus nerve stimulation: an evolving adjunctive treatment for cardiac disease.
        Anatol J Cardiol. 2016; 16: 804-810
        • Polak T.
        • Markulin F.
        • Ehlis A.C.
        • Langer J.B.
        • Ringel T.M.
        • Fallgatter A.J.
        Far field potentials from brain stem after transcutaneous vagus nerve stimulation: optimization of stimulation and recording parameters.
        J Neural Transm. 2009; 116: 1237-1242
        • Fallgatter A.J.
        • Ehlis A.C.
        • Ringel T.M.
        • Herrmann M.J.
        Age effect on far field potentials from the brain stem after transcutaneous vagus nerve stimulation.
        Int J Psychophysiol. 2005; 56: 37-43
        • Fallgatter A.J.
        • Neuhauser B.
        • Herrmann M.J.
        • et al.
        Far field potentials from the brain stem after transcutaneous vagus nerve stimulation.
        J Neural Transm. 2003; 110: 1437-1443
        • Young J.R.
        • Smani S.A.
        • Mischel N.A.
        • Kritzer M.D.
        • Appelbaum L.G.
        • Patkar A.A.
        Non-invasive brain stimulation modalities for the treatment and prevention of opioid use disorder: a systematic review of the literature.
        J Addict Dis. 2020; 38: 186-199
        • Cai L.
        • Lu K.
        • Chen X.
        • Huang J.Y.
        • Zhang B.P.
        • Zhang H.
        Auricular vagus nerve stimulation protects against postoperative cognitive dysfunction by attenuating neuroinflammation and neurodegeneration in aged rats.
        Neurosci Lett. 2019; 703: 104-110
        • Jiang Y.
        • Cao Z.
        • Ma H.
        • et al.
        Auricular vagus nerve stimulation exerts antiinflammatory effects and immune regulatory function in a 6-OHDA model of Parkinson's disease.
        Neurochem Res. 2018; 43: 2155-2164
        • Jiang Y.
        • Li L.
        • Ma J.
        • Zhang L.
        • Niu F.
        • Feng T.
        Auricular vagus nerve stimulation promotes functional recovery and enhances the post-ischemic angiogenic response in an ischemia/reperfusion rat model.
        Neurochem Int. 2016; 97: 73-82
        • Ay I.
        • Napadow V.
        • Ay H.
        Electrical stimulation of the vagus nerve dermatome in the external ear is protective in rat cerebral ischemia.
        Brain Stimul. 2015; 8: 7-12
        • Sclocco R.
        • Garcia R.G.
        • Kettner N.W.
        • et al.
        Stimulus frequency modulates brainstem response to respiratory-gated transcutaneous auricular vagus nerve stimulation.
        Brain Stimul. 2020; 13: 970-978
        • Garcia R.G.
        • Lin R.L.
        • Lee J.
        • et al.
        Modulation of brainstem activity and connectivity by respiratory-gated auricular vagal afferent nerve stimulation in migraine patients.
        Pain. 2017; 158: 1461-1472
        • Sclocco R.
        • Garcia R.G.
        • Gabriel A.
        • Kettner N.W.
        • Napadow V.
        • Barbieri R.
        Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) effects on autonomic outflow in hypertension.
        Annu Int Conf IEEE Eng Med Biol Soc. 2017; 2017: 3130-3133
        • Napadow V.
        • Edwards R.R.
        • Cahalan C.M.
        • et al.
        Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation.
        Pain Med. 2012; 13: 777-789
        • Dabiri B.
        • Kampusch S.
        • Geyer S.H.
        • et al.
        High-resolution episcopic imaging for visualization of dermal arteries and nerves of the auricular cymba conchae in humans.
        Front Neuroanat. 2020; 14: 22
        • Van de Steene T.
        • Tanghe E.
        • Tarnaud T.
        • et al.
        Sensitivity study of neuronal excitation and cathodal blocking thresholds of myelinated axons for percutaneous auricular vagus nerve stimulation.
        IEEE Trans Biomed Eng. 2020; 67: 3276-3287
        • Gomolka R.S.
        • Kampusch S.
        • Kaniusas E.
        • Thürk F.
        • Széles J.C.
        • Klonowski W.
        Higuchi fractal dimension of heart rate variability during percutaneous auricular vagus nerve stimulation in healthy and diabetic subjects.
        Front Physiol. 2018; 9: 1162
        • Kampusch S.
        • Kaniusas E.
        • Széles J.C.
        Modulation of muscle tone and sympathovagal balance in cervical dystonia using percutaneous stimulation of the auricular vagus nerve.
        Artif Organs. 2015; 39: E202-E212
        • Weise D.
        • Pargac C.
        • Pelz J.O.
        • Rumpf J.J.
        • Fricke C.
        • Classen J.
        Assessing blink reflex circuits by three different afferent routes in Parkinson's disease.
        Clin Neurophysiol. 2019; 130: 582-587
        • Weise D.
        • Adamidis M.
        • Pizzolato F.
        • Rump J.J.
        • Fricke C.
        • Classen J.
        Assessment of brainstem function with auricular branch of vagus nerve stimulation in Parkinson's disease.
        PLoS One. 2015; 10: e0120786
        • Polak T.
        • Dresler T.
        • Zeller J.B.
        • et al.
        Vagus somatosensory evoked potentials are delayed in Alzheimer's disease, but not in major depression.
        Eur Arch Psychiatry Clin Neurosci. 2014; 264: 263-267
        • Polak T.
        • Zeller D.
        • Fallgatter A.J.
        • Metzger F.G.
        Vagus somatosensory-evoked potentials are prolonged in patients with multiple sclerosis with brainstem involvement.
        Neuroreport. 2013; 24: 251-253
        • Peter N.
        • Kleinjung T.
        Neuromodulation for tinnitus treatment: an overview of invasive and non-invasive techniques.
        J Zhejiang Univ Sci B. 2019; 20: 116-130
        • Capone F.
        • Miccinilli S.
        • Pellegrino G.
        • et al.
        Transcutaneous vagus nerve stimulation combined with robotic rehabilitation improves upper limb function after stroke.
        Neural Plast. 2017; 2017: 7876507
        • Schoenen J.
        • Roberta B.
        • Magis D.
        • Coppola G.
        Noninvasive neurostimulation methods for migraine therapy: the available evidence.
        Cephalalgia. 2016; 36: 1170-1180
        • Yu L.
        • Wang S.
        • Zhou X.
        • et al.
        Chronic intermittent low-level stimulation of tragus reduces cardiac autonomic remodeling and ventricular arrhythmia inducibility in a post-infarction canine model.
        JACC Clin Electrophysiol. 2016; 2: 330-339
        • Wang Z.
        • Yu L.
        • Wang S.
        • et al.
        Chronic intermittent low-level transcutaneous electrical stimulation of auricular branch of vagus nerve improves left ventricular remodeling in conscious dogs with healed myocardial infarction.
        Circ Heart Fail. 2014; 7: 101421
        • Yu L.
        • Scherlag B.J.
        • Li S.
        • et al.
        Low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve: a noninvasive approach to treat the initial phase of atrial fibrillation.
        Heart Rhythm. 2013; 10: 428-435
        • Kapa S.
        • Callans D.J.
        Looking beyond the ablation shore, treating atrial fibrillation from afar: integrating anatomic, physiologic, neurologic, and cardiovascular principles into novel therapies.
        J Am Coll Cardiol. 2015; 65: 876-878
        • Wang Z.
        • Zhou X.
        • Sheng X.
        • Yu L.
        • Jiang H.
        Unilateral low-level transcutaneous electrical vagus nerve stimulation: a novel noninvasive treatment for myocardial infarction.
        Int J Cardiol. 2015; 190: 9-10
        • Wang Z.
        • Zhou X.
        • Sheng X.
        • Yu L.
        • Jiang H.
        Noninvasive vagal nerve stimulation for heart failure: was it practical or just a stunt?.
        Int J Cardiol. 2015; 187: 637-638
        • Sukasem A.
        • Cakmak Y.O.
        • Khwaounjoo P.
        • Gharibans A.
        • Du P.
        The effects of low-and high-frequency non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) on gastric slow waves evaluated using in vivo high-resolution mapping in porcine.
        Neurogastroenterol Motil. 2020; 32: e13852
        • Qureshi I.S.
        • Datta-Chaudhuri T.
        • Tracey K.J.
        • Pavlov V.A.
        • Chen A.C.H.
        Auricular neural stimulation as a new non-invasive treatment for opioid detoxification.
        Bioelectron Med. 2020; 6: 7
        • Usichenko T.
        • Hacker H.
        • Lotze M.
        Transcutaneous auricular vagal nerve stimulation (taVNS) might be a mechanism behind the analgesic effects of auricular acupuncture.
        Brain Stimul. 2017; 10: 1042-1044
        • Burger A.M.
        • Van der Does W.
        • Brosschot J.F.
        • Verkuil B.
        From ear to eye? No effect of transcutaneous vagus nerve stimulation on human pupil dilation: a report of three studies.
        Biol Psychol. 2020; 152: 107863
        • Burger A.M.
        • Van Diest I.
        • van der Does W.
        • et al.
        Transcutaneous vagus nerve stimulation and extinction of prepared fear: a conceptual non-replication.
        Sci Rep. 2018; 8: 11471
        • Yakunina N.
        • Kim S.S.
        • Nam E.C.
        Optimization of transcutaneous vagus nerve stimulation using functional MRI.
        Neuromodulation. 2017; 20: 290-300
        • Song G.F.
        • Wang H.Y.
        • Wu C.J.
        • Li X.
        • Yang F.Y.
        A retrospective study of transcutaneous vagus nerve stimulation for poststroke epilepsy.
        Medicine. 2018; 97: e11625
        • Janner H.
        • Klausenitz C.
        • Gürtler N.
        • Hahnenkamp K.
        • Usichenko T.I.
        Effects of electrical transcutaneous vagus nerve stimulation on the perceived intensity of repetitive painful heat stimuli: a blinded placebo- and sham-controlled randomized crossover investigation.
        Anesth Analg. 2018; 126: 2085-2092
        • Xiong J.
        • Xue F.S.
        • Liu J.H.
        • et al.
        Transcutaneous vagus nerve stimulation may attenuate postoperative cognitive dysfunction in elderly patients.
        Med Hypotheses. 2009; 73: 938-941
        • Li H.
        • Zhang J.B.
        • Xu C.
        • et al.
        Effects and mechanisms of auricular vagus nerve stimulation on high-fat-diet–induced obese rats.
        Nutrition. 2015; 31: 1416-1422
        • Kampusch S.
        • Kaniusas E.
        • Széles J.C.
        Expected effects of auricular vagus nerve stimulation in dystonia.
        Biomed Tech. 2013; 58https://doi.org/10.1515/bmt-2013-4033
        • Chen M.
        • Zhou X.
        • Liu Q.
        • et al.
        Left-sided noninvasive vagus nerve stimulation suppresses atrial fibrillation by upregulating atrial gap junctions in canines.
        J Cardiovasc Pharmacol. 2015; 66: 593-599
        • Chen M.
        • Yu L.
        • Liu Q.
        • et al.
        Low level tragus nerve stimulation is a non-invasive approach for anti-atrial fibrillation via preventing the loss of connexins.
        Int J Cardiol. 2015; 179: 144-145
        • Stavrakis S.
        • Stoner J.A.
        • Humphrey M.B.
        • et al.
        TREAT AF (transcutaneous electrical vagus nerve stimulation to suppress atrial fibrillation): a randomized clinical trial.
        JACC Clin Electrophysiol. 2020; 6: 282-291
        • Stavrakis S.
        • Humphrey M.B.
        • Po S.S.
        Reply: vagal modulation of atrial fibrillation.
        J Am Coll Cardiol. 2015; 66: 978
        • Chen M.
        • Yu L.
        • Liu Q.
        • et al.
        Noninvasive vagus nerve stimulation: a novel promising modulator for cardiac autonomic nerve system dysfunction.
        Int J Cardiol. 2015; 187: 338-339
        • Chen M.
        • Yu L.
        • Ouyang F.
        • et al.
        The right side or left side of noninvasive transcutaneous vagus nerve stimulation: based on conventional wisdom or scientific evidence?.
        Int J Cardiol. 2015; 187: 44-45
        • Yu L.
        • Li X.
        • Huang B.
        • et al.
        Atrial fibrillation in acute obstructive sleep apnea: autonomic nervous mechanism and modulation.
        J Am Heart Assoc. 2017; 6: e006264
        • Yu L.
        • Huang B.
        • Po S.S.
        • et al.
        Low-level tragus stimulation for the treatment of ischemia and reperfusion injury in patients with ST-segment elevation myocardial infarction: a proof-of-concept study.
        JACC Cardiovasc Interv. 2017; 10: 1511-1520
        • Wang Z.
        • Yu L.
        • Huang B.
        • et al.
        Low-level transcutaneous electrical stimulation of the auricular branch of vagus nerve ameliorates left ventricular remodeling and dysfunction by downregulation of matrix metalloproteinase 9 and transforming growth factor β1.
        J Cardiovasc Pharmacol. 2015; 65: 342-348
        • Kaniusas E.
        • Kampusch S.
        • Tittgemeyer M.
        • et al.
        Current directions in the auricular vagus nerve stimulation I - a physiological perspective.
        Front Neurosci. 2019; 13: 854
        • Kaniusas E.
        • Kampusch S.
        • Tittgemeyer M.
        • et al.
        Current directions in the auricular vagus nerve stimulation II - an engineering perspective.
        Front Neurosci. 2019; 13: 772
        • Peng L.
        • Mu K.
        • Liu A.
        • et al.
        Transauricular vagus nerve stimulation at auricular acupoints Kindey (CO10), Yidan (CO11), Liver (CO12) and Shenmen (TF4) can induce auditory and limbic cortices activation measured by fMRI.
        Hear Res. 2018; 359: 1-12
        • Yuan H.
        • Silberstein S.D.
        Vagus nerve and vagus nerve stimulation, a comprehensive review: part II.
        Headache. 2016; 56: 259-266
        • Howland R.H.
        New developments with vagus nerve stimulation therapy.
        J Psychosoc Nurs Ment Health Serv. 2014; 52: 11-14
        • Polak T.
        • Herrmann M.J.
        • Müller L.D.
        • et al.
        Near-infrared spectroscopy (NIRS) and vagus somatosensory evoked potentials (VSEP) in the early diagnosis of Alzheimer's disease: rationale, design, methods, and first baseline data of the Vogel study.
        J Neural Transm. 2017; 124: 1473-1488
        • Nonis R.
        • D'Ostilio K.
        • Schoenen J.
        • Magis D.
        Evidence of activation of vagal afferents by non-invasive vagus nerve stimulation: an electrophysiological study in healthy volunteers.
        Cephalalgia. 2017; 37: 1285-1293
        • van der Vlis T.A.M.B.
        • Schijns O.E.M.G.
        • Schaper F.L.W.V.J.
        • Hoogland G.
        • Kubben P.
        • Wagner L.
        Deep brain stimulation of the anterior nucleus of the thalamus for drug-resistant epilepsy.
        Neurosurg Rev. 2019; 42: 287-296
        • Barbella G.
        • Cocco I.
        • Freri E.
        • et al.
        Transcutaneous vagal nerve stimulation (t-VNS): an adjunctive treatment option for refractory epilepsy.
        Seizure. 2018; 60: 115-119
        • Juel J.
        • Brock C.
        • Olesen S.S.
        • et al.
        Acute physiological and electrical accentuation of vagal tone has no effect on pain or gastrointestinal motility in chronic pancreatitis.
        J Pain Res. 2017; 10: 1347-1355
        • Usichenko T.
        • Laqua R.
        • Leutzow B.
        • Lotze M.
        Preliminary findings of cerebral responses on transcutaneous vagal nerve stimulation on experimental heat pain.
        Brain Imaging Behav. 2017; 11: 30-37
        • Laqua R.
        • Leutzow B.
        • Wendt M.
        • Usichenko T.
        Transcutaneous vagal nerve stimulation may elicit anti- and pro-nociceptive effects under experimentally-induced pain - a crossover placebo-controlled investigation.
        Auton Neurosci. 2014; 185: 120-122
        • Janitzky K.
        Impaired phasic discharge of locus coeruleus neurons based on persistent high tonic discharge-a new hypothesis with potential implications for neurodegenerative diseases.
        Front Neurol. 2002; 11: 371
        • Marshall R.
        • Taylor I.
        • Lahr C.
        • et al.
        Bioelectrical stimulation for the reduction of inflammation in inflammatory bowel disease.
        Clin Med Insights Gastroenterol. 2015; 8: 55-59
        • Rong P.J.
        • Zhao J.J.
        • Li Y.Q.
        • et al.
        Auricular acupuncture and biomedical research—a promising Sino-Austrian research cooperation.
        Chin J Integr Med. 2015; 21: 887-894
        • Sun H.
        • Nasi-Er B.G.
        • Wang X.
        • et al.
        Tragus nerve stimulation suppresses post-infarction ventricular arrhythmia by modulating autonomic activity and heterogeneities of cardiac receptor distribution.
        Med Sci Monit. 2020; 26: e922277
        • Chen S.H.
        • Chen H.C.
        • Hsieh C.L.
        • Chao P.M.
        Electric stimulation of ears accelerates body weight loss mediated by high-fat to low-fat diet switch accompanied by increased white adipose tissue browning in C57BL/6J mice.
        BMC Complement Altern Med. 2018; 18: 323
        • Afanasiev S.A.
        • Pavliukova E.N.
        • Kuzmichkina M.A.
        • Rebrova T.Y.
        • Anfinogenova Y.
        • Likhomanov K.S.
        Nonpharmacological correction of hypersympatheticotonia in patients with chronic coronary insufficiency and severe left ventricular dysfunction.
        Ann Noninvasive Electrocardiol. 2016; 21: 548-556
        • Frangos E.
        • Richards E.A.
        • Bushnell M.C.
        Do the psychological effects of vagus nerve stimulation partially mediate vagal pain modulation?.
        Neurobiol Pain. 2017; 1: 37-45
        • Hansen N.
        Memory reinforcement and attenuation by activating the human locus coeruleus via transcutaneous vagus nerve stimulation.
        Front Neurosci. 2019; 12: 955
        • Vázquez Oliver A.
        • Brambilla Pisoni C.
        • Domingo Gainza M.
        • Maldonado R.
        • Ivorra A.
        • Ozaita A.
        Auricular transcutaneous vagus nerve stimulation improves memory persistence in naïve mice and in an intellectual disability mouse model.
        Brain Stimul. 2020; 13: 494-498
        • Broncel A.
        • Bocian R.
        • Kłos Wojtczak P.
        • Kulbat Warycha K.
        • Konopacki J.
        Vagal nerve stimulation as a promising tool in the improvement of cognitive disorders.
        Brain Res Bull. 2020; 155: 37-47
        • Cakmak Y.O.
        Concerning auricular vagal nerve stimulation: occult neural networks.
        Front Hum Neurosci. 2019; 13: 421
        • Kutlu N.
        • Özden A.V.
        • Alptekin H.K.
        • Alptekin J.Ö.
        The impact of auricular vagus nerve stimulation on pain and life quality in patients with fibromyalgia syndrome.
        Biomed Res Int. 2020; 2020: 8656218
        • Yang A.C.
        • Zhang J.G.
        • Rong P.J.
        • Liu H.G.
        • Chen N.
        • Zhu B.
        A new choice for the treatment of epilepsy: electrical auricula-vagus-stimulation.
        Med Hypotheses. 2011; 77: 244-245
        • Polak T.
        • Ehlis A.C.
        • Langer J.B.
        • et al.
        Non-invasive measurement of vagus activity in the brainstem - a methodological progress towards earlier diagnosis of dementias?.
        J Neural Transm. 2007; 114: 613-619
        • Stavrakis S.
        • Humphrey M.B.
        • Scherlag B.J.
        • et al.
        Low-level transcutaneous electrical vagus nerve stimulation suppresses atrial fibrillation.
        J Am Coll Cardiol. 2015; 65: 867-875
        • Krul S.P.J.
        • Berger W.R.
        • Veldkamp M.W.
        • et al.
        Treatment of atrial and ventricular arrhythmias through autonomic modulation.
        JACC Clin Electrophysiol. 2015; 1: 496-508
        • Wang Z.
        • Zhou X.
        • Zhou L.
        • Yu L.
        • Jiang H.
        Noninvasive vagus nerve stimulation: a novel feasible approach for cardioprotection during ischemia-reperfusion injury.
        Int J Cardiol. 2015; 191: 13-14
        • Machhada A.
        • Gourine A.V.
        • Ackland G.L.
        Vagal modulation of atrial fibrillation.
        J Am Coll Cardiol. 2015; 66: 977-978
        • Bretherton B.
        • Deuchars S.A.
        • Deuchars J.
        Messages from the auricle: limiting progression of heart failure with preserved ejection fraction through transcutaneous nerve stimulation of nerves in the external ear.
        Exp Physiol. 2019; 104: 11-12
        • Tran N.
        • Asad Z.
        • Elkholey K.
        • Scherlag B.J.
        • Po S.S.
        • Stavrakis S.
        Autonomic neuromodulation acutely ameliorates left ventricular strain in humans.
        J Cardiovasc Transl Res. 2019; 12: 221-230
        • Li S.
        • Zhou X.
        • Yu L.
        • Jiang H.
        Low level non-invasive vagus nerve stimulation: a novel feasible therapeutic approach for atrial fibrillation.
        Int J Cardiol. 2015; 182: 189-190
        • Hou Y.
        • Zhou Q.
        • Po S.S.
        Neuromodulation for cardiac arrhythmia.
        Heart Rhythm. 2016; 13: 584-592
        • Zhou L.
        • Filiberti A.
        • Humphrey M.B.
        • et al.
        Low-level transcutaneous vagus nerve stimulation attenuates cardiac remodelling in a rat model of heart failure with preserved ejection fraction.
        Exp Physiol. 2019; 104: 28-38
        • Zhou X.
        • Zhou L.
        • Wang S.
        • et al.
        The use of noninvasive vagal nerve stimulation to inhibit sympathetically induced sinus node acceleration: a potential therapeutic approach for inappropriate sinus tachycardia.
        J Cardiovasc Electrophysiol. 2016; 27: 217-223
        • Kassir R.
        • Barthelemy J.C.
        • Roche F.
        • Tiffet O.
        Comments on the article: occipital C1-C2 neuromodulation decreases body mass and fat stores and modifies activity of the autonomic nervous system in morbidly obese patients–a pilot study.
        Obes Surg. 2016; 26: 384-385
        • Henssen D.J.H.A.
        • Derks B.
        • van Doorn M.
        • Verhoogt N.
        • Van Cappellen van Walsum A.M.
        • Staats P.
        Vagus nerve stimulation for primary headache disorders: an anatomical review to explain a clinical phenomenon.
        Cephalalgia. 2019; 39: 1180-1194
        • Maharjan A.
        • Wang E.
        • Peng M.
        • Cakmak Y.O.
        Improvement of olfactory function with high frequency non-invasive auricular electrostimulation in healthy humans.
        Front Neurosci. 2018; 12: 225
        • Safi S.
        • Ellrich J.
        • Neuhuber W.
        Myelinated axons in the auricular branch of the human vagus nerve.
        Anat Rec. 2016; 299: 1184-1191
        • Kaniusas E.
        • Samoudi A.M.
        • Kampusch S.
        • et al.
        Stimulation pattern efficiency in percutaneous auricular vagus nerve stimulation: experimental versus numerical data.
        IEEE Trans Biomed Eng. 2020; 67: 1921-1935
        • Samoudi A.M.
        • Kampusch S.
        • Tanghe E.
        • et al.
        Numerical modeling of percutaneous auricular vagus nerve stimulation: a realistic 3D model to evaluate sensitivity of neural activation to electrode position.
        Med Biol Eng Comput. 2017; 55: 1763-1772
        • Fuentes Márquez P.
        • Cabrera Martos I.
        • Valenza M.C.
        Physiotherapy interventions for patients with chronic pelvic pain: a systematic review of the literature.
        Physiother Theory Pract. 2019; 35: 1131-1138
        • Noé E.
        • Ferri J.
        • Colomer C.
        • et al.
        Feasibility, safety and efficacy of transauricular vagus nerve stimulation in a cohort of patients with disorders of consciousness.
        Brain Stimul. 2020; 13: 427-429
        • Redgrave J.N.
        • Moore L.
        • Oyekunle T.
        • et al.
        Transcutaneous auricular vagus nerve stimulation with concurrent upper limb repetitive task practice for poststroke motor recovery: a pilot study.
        J Stroke Cerebrovasc Dis. 2018; 27: 1998-2005
        • Nasi-Er B.G.
        • Wenhui Z.
        • HuaXin S.
        • et al.
        Vagus nerve stimulation reduces ventricular arrhythmias and increases ventricular electrical stability.
        Pacing Clin Electrophysiol. 2019; 42: 247-256
        • Liu C.H.
        • Lin Y.W.
        • Hsu H.C.
        • Liu H.J.
        • Lin W.J.
        • Hsieh C.L.
        Electroacupuncture at ST36-ST37 and at ear ameliorates hippocampal mossy fiber sprouting in kainic acid-induced epileptic seizure rats.
        Biomed Res Int. 2014; 2014: 756019
        • Bermejo P.
        • López M.
        • Larraya I.
        • et al.
        Innervation of the human cavum conchae and auditory canal: anatomical basis for transcutaneous auricular nerve stimulation.
        Biomed Res Int. 2017; 2017: 7830919
        • Yuen A.W.
        • Sander J.W.
        Can natural ways to stimulate the vagus nerve improve seizure control?.
        Epilepsy Behav. 2017; 67: 105-110
        • Li T.T.
        • Wang Z.J.
        • Yang S.B.
        • et al.
        Transcutaneous electrical stimulation at auricular acupoints innervated by auricular branch of vagus nerve pairing tone for tinnitus: study protocol for a randomized controlled clinical trial.
        Trials. 2015; 16: 101
        • Wang Z.
        • Yu L.
        • Chen M.
        • Wang S.
        • Jiang H.
        Transcutaneous electrical stimulation of auricular branch of vagus nerve: a noninvasive therapeutic approach for post-ischemic heart failure.
        Int J Cardiol. 2014; 177: 676-677
        • Busch V.
        • Zeman F.
        • Heckel A.
        • Menne F.
        • Ellrich J.
        • Eichhammer P.
        The effect of transcutaneous vagus nerve stimulation on pain perception—an experimental study.
        Brain Stimul. 2013; 6: 202-209
        • Burger A.M.
        • Van der Does W.
        • Thayer J.F.
        • Brosschot J.F.
        • Verkuil B.
        Transcutaneous vagus nerve stimulation reduces spontaneous but not induced negative thought intrusions in high worriers.
        Biol Psychol. 2019; 142: 80-89
        • He B.
        • Lu Z.
        • He W.
        • Huang B.
        • Jiang H.
        Autonomic modulation by electrical stimulation of the parasympathetic nervous system: an emerging intervention for cardiovascular diseases.
        Cardiovasc Ther. 2016; 34: 167-171
        • Leutzow B.
        • Lange J.
        • Gibb A.
        • et al.
        Vagal sensory evoked potentials disappear under the neuromuscular block - an experimental study.
        Brain Stimul. 2013; 6: 812-816
        • Frøkjaer J.B.
        • Bergmann S.
        • Brock C.
        • et al.
        Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity.
        Neurogastroenterol Motil. 2016; 28: 592-598
        • Hasan A.
        • Wolff-Menzler C.
        • Pfeiffer S.
        • et al.
        Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized controlled pilot study.
        Eur Arch Psychiatry Clin Neurosci. 2015; 265: 589-600
        • Salama M.
        • Akan A.
        • Mueller M.R.
        Transcutaneous stimulation of auricular branch of the vagus nerve attenuates the acute inflammatory response after lung lobectomy.
        World J Surg. 2020; 44: 3167-3174
        • Kreuzer P.M.
        • Landgrebe M.
        • Resch M.
        • et al.
        Feasibility, safety and efficacy of transcutaneous vagus nerve stimulation in chronic tinnitus: an open pilot study.
        Brain Stimul. 2014; 7: 740-747
        • Straube A.
        • Ellrich J.
        • Eren O.
        • Blum B.
        • Ruscheweyh R.
        Treatment of chronic migraine with transcutaneous stimulation of the auricular branch of the vagal nerve (auricular t-VNS): a randomized, monocentric clinical trial.
        J Headache Pain. 2015; 16: 543
        • Rimmele F.
        • Jürgens T.P.
        Neuromodulation in primary headaches: current evidence and integration into clinical practice.
        Curr Opin Neurol. 2020; 33: 329-337
        • Wang S.
        • Zhai X.
        • Li S.
        • McCabe M.F.
        • Wang X.
        • Rong P.
        Transcutaneous vagus nerve stimulation induces tidal melatonin secretion and has an antidiabetic effect in Zucker fatty rats.
        PLoS One. 2015; 10: e0124195
        • Cai P.Y.
        • Bodhit A.
        • Derequito R.
        • et al.
        Vagus nerve stimulation in ischemic stroke: old wine in a new bottle.
        Front Neurol. 2014; 5: 107
        • Mercante B.
        • Ginatempo F.
        • Manca A.
        • Melis F.
        • Enrico P.
        • Deriu F.
        Anatomo-physiologic basis for auricular stimulation.
        Med Acupunct. 2018; 30: 141-150
        • Ay I.
        • Nasser R.
        • Simon B.
        • Ay H.
        Transcutaneous cervical vagus nerve stimulation ameliorates acute ischemic injury in rats.
        Brain Stimul. 2016; 9: 166-173
        • Lendvai I.S.
        • Maier A.
        • Scheele D.
        • Hurlemann R.
        • Kinfe T.M.
        Spotlight on cervical vagus nerve stimulation for the treatment of primary headache disorders: a review.
        J Pain Res. 2018; 11: 1613-1625
        • Gurel N.Z.
        • Huang M.
        • Wittbrodt M.T.
        • et al.
        Quantifying acute physiological biomarkers of transcutaneous cervical vagal nerve stimulation in the context of psychological stress.
        Brain Stimul. 2020; 13: 47-59
        • Magis D.
        • Gérard P.
        • Schoenen J.
        Transcutaneous vagus nerve stimulation (tVNS) for headache prophylaxis: initial experience.
        J Headache Pain. 2013; 14: 198
        • Muthulingam J.A.
        • Olesen S.S.
        • Hansen T.M.
        • Brock C.
        • Drewes A.M.
        • Frøkjær J.B.
        Study protocol for a randomised double-blinded, sham-controlled, prospective, cross-over clinical trial of vagal neuromodulation for pain treatment in patients with chronic pancreatitis.
        BMJ Open. 2019; 9: e029546
        • Farmer A.D.
        • Strzelczyk A.
        • Finisguerra A.
        • et al.
        International consensus based review and recommendations for minimum reporting standards in research on transcutaneous vagus nerve stimulation (version 2020).
        Front Hum Neurosci. 2021; 14 (568051. https://doi.org/10.3389/fnhum.2020.568051)

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