Skip to main content
Log in

BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

Direct vagus nerve stimulation (VNS) has proved to be an effective treatment for seizure disorder and major depression. However, since this invasive technique implies surgery, with its side-effects and relatively high financial costs, a non-invasive method to stimulate vagal afferences would be a great step forward. We studied effects of non-invasive electrical stimulation of the nerves in the left outer auditory canal in healthy subjects (n = 22), aiming to activate vagal afferences transcutaneously (t-VNS). Short-term changes in brain activation and subjective well-being induced by t-VNS were investigated by functional magnetic resonance imaging (fMRI) and psychometric assessment using the Adjective Mood Scale (AMS), a self-rating scale for current subjective feeling. Stimulation of the ear lobe served as a sham control.

fMRI showed that robust t-VNS induced BOLD-signal decreases in limbic brain areas, including the amygdala, hippocampus, parahippocampal gyrus and the middle and superior temporal gyrus. Increased activation was seen in the insula, precentral gyrus and the thalamus. Psychometric assessment revealed significant improvement of well-being after t-VNS. Ear lobe stimulation as a sham control intervention did not show similar effects in either fMRI or psychometric assessment. No significant effects on heart rate, blood pressure or peripheral microcirculation could be detected during the stimulation procedure.

Conclusions. Our study shows the feasibility and beneficial effects of transcutaneous nerve stimulation in the left auditory canal of healthy subjects. Brain activation patterns clearly share features with changes observed during invasive vagus nerve stimulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bettis DB (2005) Initiating VNS Therapy TM: a Practical Guide. http://www.vnstherapy.com/depression/hcp/THESYNAPSE/bettis.htm

  • DP Bobon YD Lapierre T Lottin (1981) ArticleTitleValidity and sensitivity of the French version of the Zerssen BfS/BfS’ self-rating mood scale during treatment with trazodone and amitriptyline Prog Neuropsychopharmacol 5 519–522 Occurrence Handle7339644 Occurrence Handle10.1016/0364-7722(81)90038-2 Occurrence Handle1:STN:280:Bi2C2srgs1M%3D

    Article  PubMed  CAS  Google Scholar 

  • JS Bodenlos S Kose JJ Borckardt Z Nahas D Shaw PM O’neil MS George (2007) ArticleTitleVagus nerve stimulation acutely alters food craving in adults with depression Appetite 48 145–153 Occurrence Handle17081655 Occurrence Handle10.1016/j.appet.2006.07.080

    Article  PubMed  Google Scholar 

  • JJ Borckardt B Anderson KF Andrew Z Nahas SA Richard TK Jackson S Kose MS George (2006) ArticleTitleAcute and long-term VNS effects on pain perception in a case of treatment-resistant depression Neurocase 12 216–220 Occurrence Handle17000590 Occurrence Handle10.1080/13554790600788094

    Article  PubMed  Google Scholar 

  • JJ Borckardt FA Kozel B Anderson A Walker MS George (2005) ArticleTitleVagus nerve stimulation affects pain perception in depressed adults Pain Res Manag 10 9–14 Occurrence Handle15782242

    PubMed  Google Scholar 

  • GM Boynton SA Engel GH Glover DJ Heeger (1996) ArticleTitleLinear systems analysis of functional magnetic resonance imaging in human V1 J Neurosci 16 4207–4221 Occurrence Handle8753882 Occurrence Handle1:CAS:528:DyaK28XjvVGktrs%3D

    PubMed  CAS  Google Scholar 

  • JG Burneo E Faught R Knowlton R Morawetz R Kuzniecky (2002) ArticleTitleWeight loss associated with vagus nerve stimulation Neurology 59 463–464 Occurrence Handle12177391 Occurrence Handle1:STN:280:DC%2BD38vitFSjtA%3D%3D

    PubMed  CAS  Google Scholar 

  • P Butow A Coates S Dunn J Bernhard C Hurny (1991) ArticleTitleOn the receiving end. IV: Validation of quality of life indicators Ann Oncol 2 597–603 Occurrence Handle1793727 Occurrence Handle1:STN:280:By2C2s3nvVE%3D

    PubMed  CAS  Google Scholar 

  • Carroll D, Moore RA, McQuay HJ, Fairman F, Tramer M, Leijon G (2001) Transcutaneous electrical nerve stimulation (TENS) for chronic pain. Cochrane Database Syst Rev CD003222

  • JH Chae Z Nahas M Lomarev S Denslow JP Lorberbaum DE Bohning MS George (2003) ArticleTitleA review of functional neuroimaging studies of vagus nerve stimulation (VNS) J Psychiatr Res 37 443–455 Occurrence Handle14563375 Occurrence Handle10.1016/S0022-3956(03)00074-8

    Article  PubMed  Google Scholar 

  • KB Clark DK Naritoku DC Smith RA Browning RA Jensen (1999) ArticleTitleEnhanced recognition memory following vagus nerve stimulation in human subjects Nat Neurosci 2 94–98 Occurrence Handle10195186 Occurrence Handle10.1038/4600 Occurrence Handle1:CAS:528:DyaK1MXhsl2ns7c%3D

    Article  PubMed  CAS  Google Scholar 

  • C Corcoran TJ Connor V O’Keane MR Garland (2005) ArticleTitleThe effects of vagus nerve stimulation on pro- and anti-inflammatory cytokines in humans: a preliminary report Neuroimmunomodulation 12 307–309 Occurrence Handle16166810 Occurrence Handle10.1159/000087109 Occurrence Handle1:CAS:528:DC%2BD2MXhtVWntrzO

    Article  PubMed  CAS  Google Scholar 

  • H Damasio (1995) Human brain anatomy in computerized images Oxford University Press Oxford

    Google Scholar 

  • Devous M (2001) Effects of VNS on regional cerebral blood flow in depressed subjects. Vagus Nerve Stimulation (VNS) for Treatment-Resistant Depression. Satellite Symposium in conjunction with the 7th World Congress of Biological Psychiatry. Berlin

  • D Ebert H Feistel A Barocka W Kaschka (1994) ArticleTitleIncreased limbic blood flow and total sleep deprivation in major depression with melancholia Psychiatr Res 55 101–109 Occurrence Handle10.1016/0925-4927(94)90004-3 Occurrence Handle1:STN:280:DC%2BD3c7nsV2nsg%3D%3D

    Article  CAS  Google Scholar 

  • AJ Fallgatter B Neuhauser MJ Herrmann AC Ehlis A Wagener P Scheuerpflug K Reiners P Riederer (2003) ArticleTitleFar field potentials from the brain stem after transcutaneous vagus nerve stimulation J Neural Transm 110 1437–1443 Occurrence Handle14666414 Occurrence Handle10.1007/s00702-003-0087-6 Occurrence Handle1:STN:280:DC%2BD3srosVKnuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • F Ferreri F Pauri P Pasqualetti R Fini G Dal Forno PM Rossini (2003) ArticleTitleMotor cortex excitability in Alzheimer’s disease: a transcranial magnetic stimulation study Ann Neurol 53 102–108 Occurrence Handle12509853 Occurrence Handle10.1002/ana.10416

    Article  PubMed  Google Scholar 

  • Gadsby JG, Flowerdew MW (2000) Transcutaneous electrical nerve stimulation and acupuncture-like transcutaneous electrical nerve stimulation for chronic low back pain. Cochrane Database Syst Rev CD000210

  • MS George Z Nahas JJ Borckardt B Anderson C Burns S Kose EB Short (2007) ArticleTitleVagus nerve stimulation for the treatment of depression and other neuropsychiatric disorders Expert Rev Neurother 7 63–74 Occurrence Handle17187498 Occurrence Handle10.1586/14737175.7.1.63

    Article  PubMed  Google Scholar 

  • RL Gould RG Brown AM Owen ET Bullmore RJ Howard (2006) ArticleTitleTask-induced deactivations during successful paired associates learning: an effect of age but not Alzheimer’s disease Neuroimage 31 812–831 Occurrence Handle10.1016/j.neuroimage.2005.12.045

    Article  Google Scholar 

  • DA Groves EM Bowman VJ Brown (2005) ArticleTitleRecordings from the rat locus coeruleus during acute vagal nerve stimulation in the anaesthetised rat Neurosci Lett 379 174–179 Occurrence Handle15843058 Occurrence Handle10.1016/j.neulet.2004.12.055 Occurrence Handle1:CAS:528:DC%2BD2MXjsVenuro%3D

    Article  PubMed  CAS  Google Scholar 

  • H Heimann H Bobon-Schrod AM Schmocker DP Bobon (1975) ArticleTitleSelf-rating of mood using a list of adjectives, Zersen’s Befindlichkeits-Skala (BS) Encephale 1 165–183 Occurrence Handle1175501 Occurrence Handle1:STN:280:CSmD383ht1I%3D

    PubMed  CAS  Google Scholar 

  • TR Henry (2002) ArticleTitleTherapeutic mechanisms of vagus nerve stimulation Neurology 59 S3–S14 Occurrence Handle12270962

    PubMed  Google Scholar 

  • TR Henry RA Bakay PB Pennell CM Epstein JR Votaw (2004) ArticleTitleBrain blood-flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: II. prolonged effects at high and low levels of stimulation Epilepsia 45 1064–1070 Occurrence Handle15329071 Occurrence Handle10.1111/j.0013-9580.2004.03104.x

    Article  PubMed  Google Scholar 

  • TR Henry RA Bakay JR Votaw PB Pennell CM Epstein TL Faber ST Grafton JM Hoffman (1998) ArticleTitleBrain 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 Occurrence Handle9738678 Occurrence Handle10.1111/j.1528-1157.1998.tb01448.x Occurrence Handle1:STN:280:DyaK1cvgvFSmug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • KK Hui J Liu N Makris RL Gollub AJ Chen CI Moore DN Kennedy BR Rosen KK Kwong (2000) ArticleTitleAcupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects Hum Brain Mapp 9 13–25 Occurrence Handle10643726 Occurrence Handle10.1002/(SICI)1097-0193(2000)9:1<13::AID-HBM2>3.0.CO;2-F Occurrence Handle1:STN:280:DC%2BD3c7gs1Ghsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • M Kalia JM Sullivan (1982) ArticleTitleBrainstem projections of sensory and motor components of the vagus nerve in the rat J Comp Neurol 211 248–265 Occurrence Handle7174893 Occurrence Handle10.1002/cne.902110304 Occurrence Handle1:STN:280:BiyD1czjvFQ%3D

    Article  PubMed  CAS  Google Scholar 

  • A Kirchner H Stefan K Bastian F Birklein (2005) ArticleTitleVagus nerve stimulation suppresses pain but has limited effects on neurogenic inflammation in humans Eur J Pain 10 449–455 Occurrence Handle16125425 Occurrence Handle10.1016/j.ejpain.2005.06.005

    Article  PubMed  Google Scholar 

  • J Kong L Ma RL Gollub J Wei X Yang D Li X Weng F Jia C Wang F Li R Li D Zhuang (2002) ArticleTitleA pilot study of functional magnetic resonance imaging of the brain during manual and electroacupuncture stimulation of acupuncture point (LI-4 Hegu) in normal subjects reveals differential brain activation between methods J Altern Complement Med 8 411–419 Occurrence Handle12230901 Occurrence Handle10.1089/107555302760253603

    Article  PubMed  Google Scholar 

  • KM Koorengevel DG Beersma MC Gordijn JA den Boer RH van den Hoofdakker (2000) ArticleTitleBody temperature and mood variations during forced desynchronization in winter depression: a preliminary report Biol Psychiatry 47 355–358 Occurrence Handle10686271 Occurrence Handle10.1016/S0006-3223(99)00225-5 Occurrence Handle1:STN:280:DC%2BD3c7ltl2ltw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • H-J Kretschmann W Weinrich (1992) Cranial neuroimaging and clinical neuroanatomy Thieme Stuttgart

    Google Scholar 

  • J Lang (1992) Klinische Anatomie des Ohres Springer Wien New York

    Google Scholar 

  • GS Malhi J Lagopoulos PB Ward V Kumari PB Mitchell GB Parker B Ivanovski P Sachdev (2004) ArticleTitleCognitive generation of affect in bipolar depression: an fMRI study Eur J Neurosci 19 741–754 Occurrence Handle14984424 Occurrence Handle10.1111/j.0953-816X.2003.03159.x

    Article  PubMed  Google Scholar 

  • BA Malow J Edwards M Marzec O Sagher D Ross G Fromes (2001) ArticleTitleVagus nerve stimulation reduces daytime sleepiness in epilepsy patients Neurology 57 879–884 Occurrence Handle11552020 Occurrence Handle1:STN:280:DC%2BD3Mrgtlahtw%3D%3D

    PubMed  CAS  Google Scholar 

  • HS Mayberg SK Brannan JL Tekell JA Silva RK Mahurin S McGinnis PA Jerabek (2000) ArticleTitleRegional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response Biol Psychiatry 48 830–843 Occurrence Handle11063978 Occurrence Handle10.1016/S0006-3223(00)01036-2 Occurrence Handle1:CAS:528:DC%2BD3cXns12gurY%3D

    Article  PubMed  CAS  Google Scholar 

  • S Multon J Schoenen (2005) ArticleTitlePain control by vagus nerve stimulation: from animal to man … and back Acta Neurol Belg 105 62–67 Occurrence Handle16076058

    PubMed  Google Scholar 

  • V Napadow N Makris J Liu NW Kettner KK Kwong KK Hui (2005) ArticleTitleEffects of electroacupuncture versus manual acupuncture on the human brain as measured by fMRI Hum Brain Mapp 24 193–205 Occurrence Handle15499576 Occurrence Handle10.1002/hbm.20081

    Article  PubMed  Google Scholar 

  • JT Narayanan R Watts N Haddad DR Labar PM Li CG Filippi (2002) ArticleTitleCerebral activation during vagus nerve stimulation: a functional MR study Epilepsia 43 1509–1514 Occurrence Handle12460253 Occurrence Handle10.1046/j.1528-1157.2002.16102.x

    Article  PubMed  Google Scholar 

  • CB Nemeroff HS Mayberg SE Krahl J McNamara A Frazer TR Henry MS George DS Charney SK Brannan (2006) ArticleTitleVNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms Neuropsychopharmacology 31 1345–1355 Occurrence Handle16641939 Occurrence Handle10.1038/sj.npp.1301082

    Article  PubMed  Google Scholar 

  • A Rauber F Kopsch (1987) Anatomie des Menschen.Lehrbuch und Atlas NumberInSeries3 Thieme Stuttgart

    Google Scholar 

  • R Ringler M Greiner L Kohlloeffel HO Handwerker C Forster (2003) ArticleTitleBOLD effects in different areas of the cerebral cortex during painful mechanical stimulation Pain 105 445–453 Occurrence Handle14527705 Occurrence Handle10.1016/S0304-3959(03)00258-6 Occurrence Handle1:STN:280:DC%2BD3svms1Kisg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • HA Sackeim AJ Rush MS George LB Marangell MM Husain Z Nahas CR Johnson S Seidman C Giller S Haines RK Simpson SuffixJr RR Goodman (2001) ArticleTitleVagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome Neuropsychopharmacology 25 713–728 Occurrence Handle11682255 Occurrence Handle10.1016/S0893-133X(01)00271-8 Occurrence Handle1:STN:280:DC%2BD3MrnsFSltg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • N Sawamoto M Honda T Okada T Hanakawa M Kanda H Fukuyama J Konishi H Shibasaki (2000) ArticleTitleExpectation of pain enhances responses to nonpainful somatosensory stimulation in the anterior cingulate cortex and parietal operculum/posterior insula: an event-related functional magnetic resonance imaging study J Neurosci 20 7438–7445 Occurrence Handle11007903 Occurrence Handle1:CAS:528:DC%2BD3cXnt1ajt70%3D

    PubMed  CAS  Google Scholar 

  • SC Schachter (2002) ArticleTitleVagus nerve stimulation: where are we? Curr Opin Neurol 15 201–206 Occurrence Handle11923636 Occurrence Handle10.1097/00019052-200204000-00013

    Article  PubMed  Google Scholar 

  • SC Schachter (2004) ArticleTitleVagus nerve stimulation: mood and cognitive effects Epilepsy Behav 5 IssueIDSuppl 1 S56–S59 Occurrence Handle14725847 Occurrence Handle10.1016/j.yebeh.2003.11.007

    Article  PubMed  Google Scholar 

  • J Sobocki G Krolczyk RM Herman A Matyja PJ Thor (2005) ArticleTitleInfluence of vagal nerve stimulation on food intake and body weight – results of experimental studies J Physiol Pharmacol 56 IssueIDSuppl 6 27–33 Occurrence Handle16340036

    PubMed  Google Scholar 

  • F Strian R Heger C Klicpera (1982) ArticleTitleThe time structure of depressive mood in schizophrenic patients Acta Psychiatr Scand 65 66–73 Occurrence Handle7187174 Occurrence Handle10.1111/j.1600-0447.1982.tb00821.x Occurrence Handle1:STN:280:BiuD2cflsFU%3D

    Article  PubMed  CAS  Google Scholar 

  • R Sucholeiki TM Alsaadi GL Morris SuffixIII JL Ulmer B Biswal WM Mueller (2002) ArticleTitlefMRI in patients implanted with a vagal nerve stimulator Seizure 11 157–162 Occurrence Handle12018958 Occurrence Handle10.1053/seiz.2001.0601

    Article  PubMed  Google Scholar 

  • J Talairach P Tournoux (1988) Co-planar stereotaxic atlas of the human brain Thieme Stuttgart

    Google Scholar 

  • RS Terry WB Tarver J Zabara (1991) ArticleTitleThe implantable neurocybernetic prosthesis system Pacing Clin Electrophysiol 14 86–93 Occurrence Handle1705341 Occurrence Handle10.1111/j.1540-8159.1991.tb04052.x Occurrence Handle1:STN:280:By6C2cbhslE%3D

    Article  PubMed  CAS  Google Scholar 

  • S Thesen O Heid E Mueller LR Schad (2000) ArticleTitleProspective acquisition correction for head motion with image-based tracking for real-time fMRI Magn Reson Med 44 457–465 Occurrence Handle10975899 Occurrence Handle10.1002/1522-2594(200009)44:3<457::AID-MRM17>3.0.CO;2-R Occurrence Handle1:STN:280:DC%2BD3cvpslWnsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • GW Thickbroom ML Byrnes DJ Edwards FL Mastaglia (2005) ArticleTitleRepetitive paired-pulse TMS at I-wave periodicity markedly increases corticospinal excitability: a new technique for modulating synaptic plasticity Clin Neurophysiol 117 61–66 Occurrence Handle16326137 Occurrence Handle10.1016/j.clinph.2005.09.010

    Article  PubMed  Google Scholar 

  • EC Ventureyra (2000) ArticleTitleTranscutaneous vagus nerve stimulation for partial onset seizure therapy. A new concept Childs Nerv Syst 16 101–102 Occurrence Handle10663816 Occurrence Handle10.1007/s003810050021 Occurrence Handle1:STN:280:DC%2BD3c7ivFyntw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • BA Vogt S Laureys (2005) ArticleTitlePosterior cingulate, precuneal and retrosplenial cortices: cytology and components of the neural network correlates of consciousness Prog Brain Res 150 205–217 Occurrence Handle16186025 Occurrence Handle10.1016/S0079-6123(05)50015-3

    Article  PubMed  Google Scholar 

  • D von Zerssen (1986) Clinical self rating scales (CSRS) of the Munich psychiatric information system (PSYCHIS München) NT Sartorius A Ban (Eds) Assessment of depression Springer Berlin Heidelberg New York

    Google Scholar 

  • D von Zerssen DM Koeller ER Rey (1970) ArticleTitleA scale for the objective evaluation of the state of subjective well-being as a method for longitudinal studies Arzneimittelforschung 20 915–918 Occurrence Handle5536059 Occurrence Handle1:STN:280:CS6D3crgsVw%3D

    PubMed  CAS  Google Scholar 

  • DM Woodbury JW Woodbury (1990) ArticleTitleEffects of vagal stimulation on experimentally induced seizures in rats Epilepsia 31 IssueIDSuppl 2 S7–S19 Occurrence Handle2226368

    PubMed  Google Scholar 

  • B Yan K Li J Xu W Wang K Li H Liu B Shan X Tang (2005) ArticleTitleAcupoint-specific fMRI patterns in human brain Neurosci Lett 383 236–240 Occurrence Handle15876491 Occurrence Handle10.1016/j.neulet.2005.04.021 Occurrence Handle1:CAS:528:DC%2BD2MXlt1Kisb8%3D

    Article  PubMed  CAS  Google Scholar 

  • A Zobel A Joe N Freymann H Clusmann J Schramm M Reinhardt HJ Biersack W Maier K Broich (2005) ArticleTitleChanges in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: an exploratory approach Psychiatry Res 139 165–179 Occurrence Handle16043331 Occurrence Handle10.1016/j.pscychresns.2005.02.010

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kraus, T., Hösl, K., Kiess, O. et al. BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation. J Neural Transm 114, 1485–1493 (2007). https://doi.org/10.1007/s00702-007-0755-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-007-0755-z

Navigation