Experimental Brain Research

, Volume 210, Issue 2, pp 217–227 | Cite as

Different resting state brain activity and functional connectivity in patients who respond and not respond to bifrontal tDCS for tinnitus suppression

  • Sven Vanneste
  • Farah Focquaert
  • Paul Van de Heyning
  • Dirk De Ridder
Research Article


Tinnitus is an ongoing phantom percept. It has been demonstrated that bifrontal transcranial direct current stimulation (tDCS) can reduce tinnitus. In this study, one group of patients reported a substantial improvement in their tinnitus perception, whereas another group described minor or no beneficial effect at all. The objective was to verify whether the activity and connectivity of the resting brain is different for people who will respond to bifrontal tDCS for tinnitus in comparison with non-responders. Higher gamma band activity was demonstrated in right primary and secondary auditory cortex and right parahippocampus for responders. It has been shown that gamma band activity in the auditory cortex is correlated with tinnitus loudness and that the anterior cingulate is involved in tinnitus distress. People who were going to respond to bifrontal tDCS also demonstrated an increased functional connectivity in the gamma band between the right dorsolateral prefrontal cortex (DLPFC) and the right parahippocampus as well as the right DLPFC and subgenual anterior cingulate cortex (sgACC). An analysis revealed that responders to bifrontal tDCS also experienced a larger suppression effect on TMS placed over the right temporal cortex (i.e. auditory cortex) than non-responders. Responders to bifrontal tDCS seem to differ in resting brain activity compared to non-responders in the right auditory cortex and parahippocampal area. They also have a different functional connectivity between DLPFC and, respectively, the sgACC and parahippocampal area. These connectivities might explain the suppression effect for both tinnitus loudness and tinnitus-related distress.


Bifrontal Transcranial direct current stimulation tDCS EEG sLORETA Functional connectivity Gamma 


  1. Alain C, Woods DL, Knight RT (1998) A distributed cortical network for auditory sensory memory in humans. Brain Res 812:23–37PubMedCrossRefGoogle Scholar
  2. Antal A, Kincses TZ, Nitsche MA, Bartfai O, Paulus W (2004a) Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence. Invest Ophthalmol Vis Sci 45:702–707PubMedCrossRefGoogle Scholar
  3. Antal A, Varga ET, Kincses TZ, Nitsche MA, Paulus W (2004b) Oscillatory brain activity and transcranial direct current stimulation in humans. Neuroreport 15:1307–1310PubMedGoogle Scholar
  4. Axelsson A, Ringdahl A (1989) Tinnitus–a study of its prevalence and characteristics. Br J Audiol 23:53–62PubMedCrossRefGoogle Scholar
  5. Beeli G, Casutt G, Baumgartner T, Jancke L (2008) Modulating presence and impulsiveness by external stimulation of the brain. Behav Brain Funct 4:33PubMedCrossRefGoogle Scholar
  6. Blood AJ, Zatorre RJ, Bermudez P, Evans AC (1999) Emotional responses to pleasant and unpleasant music correlate with activity in paralimbic brain regions. Nat Neurosci 2:382–387PubMedCrossRefGoogle Scholar
  7. Bodner M, Kroger J, Fuster JM (1996) Auditory memory cells in dorsolateral prefrontal cortex. Neuroreport 7:1905–1908PubMedCrossRefGoogle Scholar
  8. Boggio PS, Zaghi S, Lopes M, Fregni F (2008) Modulatory effects of anodal transcranial direct current stimulation on perception and pain thresholds in healthy volunteers. Eur J Neurol 15:1124–1130PubMedCrossRefGoogle Scholar
  9. Boggio PS, Zaghi S, Fregni F (2009) Modulation of emotions associated with images of human pain using anodal transcranial direct current stimulation (tDCS). Neuropsychologia 47:212–217PubMedCrossRefGoogle Scholar
  10. Boutros NN, Trautner P, Rosburg T, Korzyukov O, Grunwald T, Schaller C, Elger CE, Kurthen M (2005) Sensory gating in the human hippocampal and rhinal regions. Clin Neurophysiol 116:1967–1974PubMedCrossRefGoogle Scholar
  11. Boutros NN, Mears R, Pflieger ME, Moxon KA, Ludowig E, Rosburg T (2008) Sensory gating in the human hippocampal and rhinal regions: regional differences. Hippocampus 18:310–316PubMedCrossRefGoogle Scholar
  12. Congedo M (2002) EureKa! (Version 3.0) [Computer Software]. Knoxville, TN: NovaTech EEG Inc. Freeware available at http://www.NovaTechEEG
  13. De Ridder D, De Mulder G, Walsh V, Muggleton N, Sunaert S, Moller A (2004) Magnetic and electrical stimulation of the auditory cortex for intractable tinnitus. Case report. J Neurosurg 100:560–564PubMedCrossRefGoogle Scholar
  14. De Ridder D, Verstraeten E, Van der Kelen K, De Mulder G, Sunaert S, Verlooy J, Van de Heyning P, Moller A (2005) Transcranial magnetic stimulation for tinnitus: influence of tinnitus duration on stimulation parameter choice and maximal tinnitus suppression. Otol Neurotol 26:616–619PubMedCrossRefGoogle Scholar
  15. De Ridder D, Fransen H, Francois O, Sunaert S, Kovacs S, Van De Heyning P (2006) Amygdalohippocampal involvement in tinnitus and auditory memory. Acta Otolaryngol Suppl 12:50–53Google Scholar
  16. De Ridder D, De Mulder G, Verstraeten E, Seidman M, Elisevich K, Sunaert S, Kovacs S, Van der Kelen K, Van de Heyning P, Moller A (2007a) Auditory cortex stimulation for tinnitus. Acta Neurochir Suppl 97:451–462PubMedCrossRefGoogle Scholar
  17. De Ridder D, van der Loo E, Van der Kelen K, Menovsky T, van de Heyning P, Moller A (2007b) Theta, alpha and beta burst transcranial magnetic stimulation: brain modulation in tinnitus. Int J Med Sci 4:237–241PubMedGoogle Scholar
  18. De Ridder D, Vanneste S, van der Loo E, Plazier M, Menovsky T, van de Heyning P (2010) Burst stimulation of the auditory cortex: a new form of neurostimulation for noise-like tinnitus suppression. J Neurosurg 112:1289–1294PubMedCrossRefGoogle Scholar
  19. Eggermont JJ, Roberts LE (2004) The neuroscience of tinnitus. Trends Neurosci 27:676–682PubMedCrossRefGoogle Scholar
  20. Fregni F, Boggio PS, Nitsche MA, Marcolin MA, Rigonatti SP, Pascual-Leone A (2006a) Treatment of major depression with transcranial direct current stimulation. Bipolar Disord 8:203–204PubMedCrossRefGoogle Scholar
  21. Fregni F, Boggio PS, Nitsche MA, Rigonatti SP, Pascual-Leone A (2006b) Cognitive effects of repeated sessions of transcranial direct current stimulation in patients with depression. Depress Anxiety 23:482–484PubMedCrossRefGoogle Scholar
  22. Fuchs M, Kastner J, Wagner M, Hawes S, Ebersole JS (2002) A standardized boundary element method volume conductor model. Clin Neurophysiol 113:702–712PubMedCrossRefGoogle Scholar
  23. Grunwald T, Boutros NN, Pezer N, von Oertzen J, Fernandez G, Schaller C, Elger CE (2003) Neuronal substrates of sensory gating within the human brain. Biol Psychiatry 53:511–519PubMedCrossRefGoogle Scholar
  24. Heller AJ (2003) Classification and epidemiology of tinnitus. Otolaryngol Clin North Am 36:239–248PubMedCrossRefGoogle Scholar
  25. Jurcak V, Tsuzuki D, Dan I (2007) 10/20, 10/10, and 10/5 systems revisited: their validity as relative head-surface-based positioning systems. Neuroimage 34:1600–1611PubMedCrossRefGoogle Scholar
  26. Kahn I, Andrews-Hanna JR, Vincent JL, Snyder AZ, Buckner RL (2008) Distinct cortical anatomy linked to subregions of the medial temporal lobe revealed by intrinsic functional connectivity. J Neurophysiol 100:129–139PubMedCrossRefGoogle Scholar
  27. Kaltenbach JA (2000) Neurophysiologic mechanisms of tinnitus. J Am Acad Audiol 11:125–137PubMedGoogle Scholar
  28. Kleinjung T, Eichhammer P, Landgrebe M, Sand P, Hajak G, Steffens T, Strutz J, Langguth B (2008) Combined temporal and prefrontal transcranial magnetic stimulation for tinnitus treatment: a pilot study. Otolaryngol Head Neck Surg 138:497–501PubMedCrossRefGoogle Scholar
  29. Knight RT, Scabini D, Woods DL (1989) Prefrontal cortex gating of auditory transmission in humans. Brain Res 504:338–342PubMedCrossRefGoogle Scholar
  30. Korzyukov O, Pflieger ME, Wagner M, Bowyer SM, Rosburg T, Sundaresan K, Elger CE, Boutros NN (2007) Generators of the intracranial P50 response in auditory sensory gating. Neuroimage 35:814–826PubMedCrossRefGoogle Scholar
  31. Landgrebe M, Langguth B, Rosengarth K, Braun S, Koch A, Kleinjung T, May A, de Ridder D, Hajak G (2009) Structural brain changes in tinnitus: grey matter decrease in auditory and non-auditory brain areas. Neuroimage 46:213–218PubMedCrossRefGoogle Scholar
  32. Langguth B, Eichhammer P, Wiegand R, Marienhegen J, Maenner P, Jacob P, Hajak G (2003) Neuronavigated rTMS in a patient with chronic tinnitus. Effects of 4 weeks treatment. Neuroreport 14:977–980PubMedCrossRefGoogle Scholar
  33. Langguth B, Hajak G, Kleinjung T, Pridmore S, Sand P, Eichhammer P (2006a) Repetitive transcranial magnetic stimulation and chronic tinnitus. Acta Otolaryngol Suppl 12:102–105Google Scholar
  34. Langguth B, Zowe M, Landgrebe M, Sand P, Kleinjung T, Binder H, Hajak G, Eichhammer P (2006b) Transcranial magnetic stimulation for the treatment of tinnitus: a new coil positioning method and first results. Brain Topogr 18:241–247PubMedCrossRefGoogle Scholar
  35. Lewis JW, Beauchamp MS, DeYoe EA (2000) A comparison of visual and auditory motion processing in human cerebral cortex. Cereb Cortex 10:873–888PubMedCrossRefGoogle Scholar
  36. Llinas RR, Ribary U, Jeanmonod D, Kronberg E, Mitra PP (1999) Thalamocortical dysrhythmia: a neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci USA 96:15222–15227PubMedCrossRefGoogle Scholar
  37. Londero A, Langguth B, De Ridder D, Bonfils P, Lefaucheur JP (2006) Repetitive transcranial magnetic stimulation (rTMS): a new therapeutic approach in subjective tinnitus? Neurophysiol Clin 36:145–155PubMedCrossRefGoogle Scholar
  38. Margulies DS, Kelly AM, Uddin LQ, Biswal BB, Castellanos FX, Milham MP (2007) Mapping the functional connectivity of anterior cingulate cortex. Neuroimage 37:579–588PubMedCrossRefGoogle Scholar
  39. Masten CL, Eisenberger NI, Borofsky LA, Pfeifer JH, McNealy K, Mazziotta JC, Dapretto M (2009) Neural correlates of social exclusion during adolescence: understanding the distress of peer rejection. Soc Cogn Affect Neurosci 4:143–157PubMedCrossRefGoogle Scholar
  40. Meeus O, Blaivie C, Ost J, De Ridder D, Van de Heyning P (2009) Influence of tonic and burst transcranial magnetic stimulation characteristics on acute inhibition of subjective tinnitus. Otol Neurotol 30:697–703PubMedCrossRefGoogle Scholar
  41. Miranda PC, Lomarev M, Hallett M (2006) Modeling the current distribution during transcranial direct current stimulation. Clin Neurophysiol 117:1623–1629PubMedCrossRefGoogle Scholar
  42. Mirz F, Pedersen B, Ishizu K, Johannsen P, Ovesen T, Stodkilde-Jorgensen H, Gjedde A (1999) Positron emission tomography of cortical centers of tinnitus. Hear Res 134:133–144PubMedCrossRefGoogle Scholar
  43. Mirz F, Gjedde A, Ishizu K, Pedersen CB (2000) Cortical networks subserving the perception of tinnitus–a PET study. Acta Otolaryngol Suppl 543:241–243PubMedCrossRefGoogle Scholar
  44. Mitchell TV, Morey RA, Inan S, Belger A (2005) Functional magnetic resonance imaging measure of automatic and controlled auditory processing. Neuroreport 16:457–461PubMedCrossRefGoogle Scholar
  45. Muhlau M, Rauschecker JP, Oestreicher E, Gaser C, Rottinger M, Wohlschlager AM, Simon F, Etgen T, Conrad B, Sander D (2006) Structural brain changes in tinnitus. Cereb Cortex 16:1283–1288PubMedCrossRefGoogle Scholar
  46. Muhlnickel W, Elbert T, Taub E, Flor H (1998) Reorganization of auditory cortex in tinnitus. Proc Natl Acad Sci USA 95:10340–10343PubMedCrossRefGoogle Scholar
  47. Nichols TE, Holmes AP (2002) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 15:1–25PubMedCrossRefGoogle Scholar
  48. Nitsche MA, Paulus W (2000) Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol 527 Pt 3: 633–639Google Scholar
  49. Nitsche MA, Paulus W (2001) Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology 57:1899–1901PubMedGoogle Scholar
  50. Nitsche MA, Nitsche MS, Klein CC, Tergau F, Rothwell JC, Paulus W (2003) Level of action of cathodal DC polarisation induced inhibition of the human motor cortex. Clin Neurophysiol 114:600–604PubMedCrossRefGoogle Scholar
  51. Norena A, Cransac H, Chery-Croze S (1999) Towards an objectification by classification of tinnitus. Clin Neurophysiol 110:666–675PubMedCrossRefGoogle Scholar
  52. Pascual-Marqui RD (2002) Standardized low-resolution brain electromagnetic tomography (sLORETA): technical details. Methods Find Exp Clin Pharmacol 24 (Suppl D): 5–12Google Scholar
  53. Pascual-Marqui R (2007a) Discrete, 3D distributed, linear imaging methods of electric neuronal activity. Part 1: exact, zero error localization. http://arxiv.org/abs/0710.3341
  54. Pascual-Marqui R (2007b) Instantaneous and lagged measurements of linear and nonlinear dependence between groups of multivariate time series: frequency decomposition. http://arxiv.org/abs/0711.1455
  55. Plewnia C, Reimold M, Najib A, Reischl G, Plontke SK, Gerloff C (2007) Moderate therapeutic efficacy of positron emission tomography-navigated repetitive transcranial magnetic stimulation for chronic tinnitus: a randomised, controlled pilot study. J Neurol Neurosurg Psychiatr 78:152–156PubMedCrossRefGoogle Scholar
  56. Pridmore S, Fernandes Filho JA, Nahas Z, Liberatos C, George MS (1998) Motor threshold in transcranial magnetic stimulation: a comparison of a neurophysiological method and a visualization of movement method. J ECT 14:25–27PubMedGoogle Scholar
  57. Rauschecker JP, Leaver AM, Muhlau M (2010) Tuning out the noise: limbic-auditory interactions in tinnitus. Neuron 66:819–826PubMedCrossRefGoogle Scholar
  58. Rossi S, Ferro M, Cincotta M, Ulivelli M, Bartalini S, Miniussi C, Giovannelli F, Passero S (2007) A real electro-magnetic placebo (REMP) device for sham transcranial magnetic stimulation (TMS). Clin Neurophysiol 118:709–716PubMedCrossRefGoogle Scholar
  59. Schlee W, Hartmann T, Langguth B, Weisz N (2009) Abnormal resting-state cortical coupling in chronic tinnitus. BMC Neurosci 10:11PubMedCrossRefGoogle Scholar
  60. Schneider P, Andermann M, Wengenroth M, Goebel R, Flor H, Rupp A, Diesch E (2009) Reduced volume of Heschl’s gyrus in tinnitus. Neuroimage 45:927–939PubMedCrossRefGoogle Scholar
  61. Smits M, Kovacs S, de Ridder D, Peeters RR, van Hecke P, Sunaert S (2007) Lateralization of functional magnetic resonance imaging (fMRI) activation in the auditory pathway of patients with lateralized tinnitus. Neuroradiology 49:669–679PubMedCrossRefGoogle Scholar
  62. Tulving E, Markowitsch HJ (1997) Memory beyond the hippocampus. Curr Opin Neurobiol 7:209–216PubMedCrossRefGoogle Scholar
  63. van der Loo E, Gais S, Congedo M, Vanneste S, Plazier M, Menovsky T, Van de Heyning P, De Ridder D (2009) Tinnitus intensity dependent gamma oscillations of the contralateral auditory cortex. PLoS ONE 4: e7396: 7391–7395Google Scholar
  64. Vanneste S, Plazier M, der Loo E, de Heyning PV, Congedo M, De Ridder D (2010a) The neural correlates of tinnitus-related distress. Neuroimage 52:470–480PubMedCrossRefGoogle Scholar
  65. Vanneste S, Plazier M, Ost J, van der Loo E, Van de Heyning P, De Ridder D (2010b) Bilateral dorsolateral prefrontal cortex modulation for tinnitus by transcranial direct current stimulation: a preliminary clinical study. Exp Brain Res 202:779–785PubMedCrossRefGoogle Scholar
  66. Voisin J, Bidet-Caulet A, Bertrand O, Fonlupt P (2006) Listening in silence activates auditory areas: a functional magnetic resonance imaging study. J Neurosci 26:273–278PubMedCrossRefGoogle Scholar
  67. Weisz N, Dohrmann K, Elbert T (2007a) The relevance of spontaneous activity for the coding of the tinnitus sensation. Prog Brain Res 166:61–70PubMedCrossRefGoogle Scholar
  68. Weisz N, Muller S, Schlee W, Dohrmann K, Hartmann T, Elbert T (2007b) The neural code of auditory phantom perception. J Neurosci 27:1479–1484PubMedCrossRefGoogle Scholar
  69. Zald DH, Pardo JV (2002) The neural correlates of aversive auditory stimulation. Neuroimage 16:746–753PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sven Vanneste
    • 1
  • Farah Focquaert
    • 2
  • Paul Van de Heyning
    • 3
  • Dirk De Ridder
    • 1
  1. 1.Brai²n, TRI and Department of NeurosurgeryUniversity Hospital AntwerpEdegemBelgium
  2. 2.Department of Philosophy and Moral SciencesGhent UniversityGhentBelgium
  3. 3.Brai²n, TRI and ENTUniversity Hospital AntwerpEdegemBelgium

Personalised recommendations