Skip to main content
Top
Published in: Journal of Neural Transmission 5/2015

01-05-2015 | Neurology and Preclinical Neurological Studies - Original Article

The effect of transcutaneous vagus nerve stimulation on cortical excitability

Authors: Fioravante Capone, Giovanni Assenza, Giovanni Di Pino, Gabriella Musumeci, Federico Ranieri, Lucia Florio, Carmen Barbato, Vincenzo Di Lazzaro

Published in: Journal of Neural Transmission | Issue 5/2015

Login to get access

Abstract

There is great interest about the therapeutic potentialities of transcutaneous vagus nerve stimulation (tVNS) applied to neuropsychiatric disorders. However, the mechanisms of action of tVNS and its impact on cortical excitability are unclear. To this regard, transcranial magnetic stimulation (TMS) can be useful because it is able of evaluating non-invasively excitatory and inhibitory circuitry of the human cortex. Aim of the present study is to investigate the effects of tVNS on cerebral cortex excitability in healthy volunteers by means of TMS. Ten healthy subjects participated in this randomized placebo-controlled double-blind study. Real tVNS was administered at left external acoustic meatus, while sham stimulation was performed at left ear lobe, both of them for 60 min. We evaluated motor thresholds, motor evoked potential amplitude, recruitment curves, and short-interval intracortical inhibition (SICI) in right and left motor cortex. Such parameters were evaluated before and 60 min after the exposure to tVNS, for both the real and the sham stimulation. Cardiovascular parameters were monitored during the stimulation. A generalized linear model for repeated measures was implemented to assess the effect of time and stimulation type on cardiovascular and neurophysiological variables. SICI, a double-pulse TMS paradigm informative of GABA-A activity, was significantly increased in right motor cortex after real tVNS. Other neurophysiological parameters, as well as cardiovascular variables, remained unchanged. Our findings confirm that tVNS is a safe and effective way to stimulate vagus nerve and provide innovative data about the possible mechanisms of action that supports the potential therapeutic application of this technique.
Literature
go back to reference Antal A, Polania R, Schmidt-Samoa C, Dechent P, Paulus W (2011) Transcranial direct current stimulation over the primary motor cortex during fMRI. Neuroimage 55:590–596CrossRefPubMed Antal A, Polania R, Schmidt-Samoa C, Dechent P, Paulus W (2011) Transcranial direct current stimulation over the primary motor cortex during fMRI. Neuroimage 55:590–596CrossRefPubMed
go back to reference Ben-Menachem E (2002) Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurol 1:477–482CrossRefPubMed Ben-Menachem E (2002) Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurol 1:477–482CrossRefPubMed
go back to reference Ben-Menachem E, Hamberger A, Hedner T, Hammond EJ, Uthman BM, 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 20:221–227CrossRefPubMed Ben-Menachem E, Hamberger A, Hedner T, Hammond EJ, Uthman BM, 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 20:221–227CrossRefPubMed
go back to reference Di Lazzaro V, Restuccia D, Oliviero A, Profice P, Ferrara L, Insola A et al (1998) Magnetic transcranial stimulation at intensities below active motor threshold activates intracortical inhibitory circuits. Exp Brain Res 2:265–268CrossRef Di Lazzaro V, Restuccia D, Oliviero A, Profice P, Ferrara L, Insola A et al (1998) Magnetic transcranial stimulation at intensities below active motor threshold activates intracortical inhibitory circuits. Exp Brain Res 2:265–268CrossRef
go back to reference Di Lazzaro V, Oliviero A, Meglio M, Cioni B, Tamburrini G, Tonali P et al (2000) Direct demonstration of the effect of lorazepamon the excitability of the human motor cortex. Clin Neurophysiol 111:794–799CrossRefPubMed Di Lazzaro V, Oliviero A, Meglio M, Cioni B, Tamburrini G, Tonali P et al (2000) Direct demonstration of the effect of lorazepamon the excitability of the human motor cortex. Clin Neurophysiol 111:794–799CrossRefPubMed
go back to reference Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Dileone M, Meglio M et al (2004) Effects of vagus nerve stimulation on cortical excitability in epileptic patients. Neurology 12:2310–2312CrossRef Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Dileone M, Meglio M et al (2004) Effects of vagus nerve stimulation on cortical excitability in epileptic patients. Neurology 12:2310–2312CrossRef
go back to reference Fallgatter AJ, Neuhauser B, Herrmann MJ, Ehlis AC, Wagener A, Scheuerpflug P et al (2003) Far field potentials from the brain stem after transcutaneous vagus nerve stimulation. J Neural Transm 12:1437–1443CrossRef Fallgatter AJ, Neuhauser B, Herrmann MJ, Ehlis AC, Wagener A, Scheuerpflug P et al (2003) Far field potentials from the brain stem after transcutaneous vagus nerve stimulation. J Neural Transm 12:1437–1443CrossRef
go back to reference Grimm S, Bajbouj M (2010) Efficacy of vagus nerve stimulation in the treatment of depression. Expert Rev Neurother 10:87–92CrossRefPubMed Grimm S, Bajbouj M (2010) Efficacy of vagus nerve stimulation in the treatment of depression. Expert Rev Neurother 10:87–92CrossRefPubMed
go back to reference Groves DA, Brown VJ (2005) Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects. Neurosci Biobehav Rev 3:493–500CrossRef Groves DA, Brown VJ (2005) Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects. Neurosci Biobehav Rev 3:493–500CrossRef
go back to reference 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 3:343–346CrossRef 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 3:343–346CrossRef
go back to reference Hein E, Nowak M, Kiess O, Biermann T, Bayerlein K, Kornhuber J et al (2013) Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. J Neural Transm 5:821–827CrossRef Hein E, Nowak M, Kiess O, Biermann T, Bayerlein K, Kornhuber J et al (2013) Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. J Neural Transm 5:821–827CrossRef
go back to reference Korchounov A, Ilic TV, Ziemann U (2003) The alpha2-adrenergic agonist guanfacine reduces excitability of human motor cortex through disfacilitation and increase of inhibition. Clin Neurophysiol 114:1834–1840CrossRefPubMed Korchounov A, Ilic TV, Ziemann U (2003) The alpha2-adrenergic agonist guanfacine reduces excitability of human motor cortex through disfacilitation and increase of inhibition. Clin Neurophysiol 114:1834–1840CrossRefPubMed
go back to reference 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 11:1485–1493CrossRef 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 11:1485–1493CrossRef
go back to reference 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 5:798–804CrossRef 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 5:798–804CrossRef
go back to reference Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A et al (1993) Corticocortical inhibition in human motor cortex. J Physiol 471:501–519CrossRefPubMedCentralPubMed Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A et al (1993) Corticocortical inhibition in human motor cortex. J Physiol 471:501–519CrossRefPubMedCentralPubMed
go back to reference Langguth B, Sand P, Marek R, Landgrebe M, Frank E, Hajak G et al (2009) Allelic variation in the serotonin transporter promoter modulates cortical excitability. Biol Psychiatry 3:283–286CrossRef Langguth B, Sand P, Marek R, Landgrebe M, Frank E, Hajak G et al (2009) Allelic variation in the serotonin transporter promoter modulates cortical excitability. Biol Psychiatry 3:283–286CrossRef
go back to reference Lehtimäki J, Hyvärinen P, Ylikoski M, Bergholm M, Mäkelä JP, Aarnisalo A et al (2013) Transcutaneous vagus nerve stimulation in tinnitus: a pilot study. Acta Otolaryngol 4:378–382CrossRef Lehtimäki J, Hyvärinen P, Ylikoski M, Bergholm M, Mäkelä JP, Aarnisalo A et al (2013) Transcutaneous vagus nerve stimulation in tinnitus: a pilot study. Acta Otolaryngol 4:378–382CrossRef
go back to reference Nemeroff CB, Mayberg HS, Krahl SE, McNamara J, Frazer A, Henry TR et al (2006) VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology 7:1345–1355CrossRef Nemeroff CB, Mayberg HS, Krahl SE, McNamara J, Frazer A, Henry TR et al (2006) VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology 7:1345–1355CrossRef
go back to reference Polak T, Markulin F, Ehlis AC, Langer JB, Ringel TM, Fallgatter AJ (2009) Far field potentials from brain stem after transcutaneous vagus nerve stimulation: optimization of stimulation and recording parameters. J Neural Transm 10:1237–1242CrossRef Polak T, Markulin F, Ehlis AC, Langer JB, Ringel TM, Fallgatter AJ (2009) Far field potentials from brain stem after transcutaneous vagus nerve stimulation: optimization of stimulation and recording parameters. J Neural Transm 10:1237–1242CrossRef
go back to reference Rong PJ, Fang JL, Wang LP, Meng H, Liu J, Ma YG 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 12:255CrossRefPubMedCentralPubMed Rong PJ, Fang JL, Wang LP, Meng H, Liu J, Ma YG 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 12:255CrossRefPubMedCentralPubMed
go back to reference 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 (Engl) 2:300–304 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 (Engl) 2:300–304
go back to reference Sackeim HA, Rush AJ, George MS, Marangell LB, Husain MM, Nahas Z, Johnson CR, Seidman S, Giller C, Haines S, Simpson RK Jr, Goodman RR (2001) Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology 5:713–728CrossRef Sackeim HA, Rush AJ, George MS, Marangell LB, Husain MM, Nahas Z, Johnson CR, Seidman S, Giller C, Haines S, Simpson RK Jr, Goodman RR (2001) Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology 5:713–728CrossRef
go back to reference 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 7:115–118CrossRef 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 7:115–118CrossRef
go back to reference Sun Z, Baker W, Hiraki T, Greenberg JH (2012) The effect of right vagus nerve stimulation on focal cerebral ischemia: an experimental study in the rat. Brain Stimul 1:1–10CrossRef Sun Z, Baker W, Hiraki T, Greenberg JH (2012) The effect of right vagus nerve stimulation on focal cerebral ischemia: an experimental study in the rat. Brain Stimul 1:1–10CrossRef
go back to reference Ventureyra EC (2000) Transcutaneous vagus nerve stimulation for partial onset seizure therapy. A new concept. Childs Nerv Syst 16:101–102CrossRefPubMed Ventureyra EC (2000) Transcutaneous vagus nerve stimulation for partial onset seizure therapy. A new concept. Childs Nerv Syst 16:101–102CrossRefPubMed
Metadata
Title
The effect of transcutaneous vagus nerve stimulation on cortical excitability
Authors
Fioravante Capone
Giovanni Assenza
Giovanni Di Pino
Gabriella Musumeci
Federico Ranieri
Lucia Florio
Carmen Barbato
Vincenzo Di Lazzaro
Publication date
01-05-2015
Publisher
Springer Vienna
Published in
Journal of Neural Transmission / Issue 5/2015
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI
https://doi.org/10.1007/s00702-014-1299-7

Other articles of this Issue 5/2015

Journal of Neural Transmission 5/2015 Go to the issue