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Tinnitus: perspectives from human neuroimaging

An Erratum to this article was published on 30 September 2015

Abstract

Tinnitus is the perception of phantom sound in the absence of a corresponding external source. It is a highly prevalent disorder, and most cases are caused by cochlear injury that leads to peripheral deafferentation, which results in adaptive changes in the CNS. In this article we critically assess the recent neuroimaging studies in individuals with tinnitus that suggest that the disorder is accompanied by functional and structural brain abnormalities in distributed auditory and non-auditory brain regions. Moreover, we consider how the identification of the neuronal mechanisms underlying the different forms of tinnitus would benefit from larger studies, replication and comprehensive clinical assessment of patients.

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Figure 1: The human auditory pathway.
Figure 2: Noise-trauma-associated changes in the auditory pathway of animals.
Figure 3: Altered activity and connectivity in distributed brain areas.

References

  1. Moller, A. R. Tinnitus: presence and future. Prog. Brain Res. 166, 3–16 (2007).

    CAS  PubMed  Google Scholar 

  2. Jastreboff, P. J. Phantom auditory perception (tinnitus): mechanisms of generation and perception. Neurosci. Res. 8, 221–254 (1990).

    CAS  PubMed  Google Scholar 

  3. Flor, H. et al. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature 375, 482–484 (1995).

    CAS  PubMed  Google Scholar 

  4. Norena, A., Micheyl, C., Chery-Croze, S. & Collet, L. Psychoacoustic characterization of the tinnitus spectrum: implications for the underlying mechanisms of tinnitus. Audiol. Neurootol. 7, 358–369 (2002).

    PubMed  Google Scholar 

  5. Langguth, B., Kreuzer, P. M., Kleinjung, T. & De Ridder, D. Tinnitus: causes and clinical management. Lancet Neurol. 12, 920–930 (2013).

    PubMed  Google Scholar 

  6. Axelsson, A. & Ringdahl, A. Tinnitus — a study of its prevalence and characteristics. Br. J. Audiol. 23, 53–62 (1989).

    CAS  PubMed  Google Scholar 

  7. Shargorodsky, J., Curhan, G. C. & Farwell, W. R. Prevalence and characteristics of tinnitus among US adults. Am. J. Med. 123, 711–718 (2010).

    PubMed  Google Scholar 

  8. Nondahl, D. M. et al. Generational differences in the reporting of tinnitus. Ear Hear. 33, 640–644 (2012).

    PubMed  PubMed Central  Google Scholar 

  9. Helfer, T. M. Noise-induced hearing injuries, active component, U. S. Armed Forces, 2007–2010. MSMR 18, 7–10 (2011).

    PubMed  Google Scholar 

  10. Langguth, B. A review of tinnitus symptoms beyond 'ringing in the ears': a call to action. Curr. Med. Res. Opin. 27, 1635–1643 (2011).

    PubMed  Google Scholar 

  11. Hebert, S., Canlon, B. & Hasson, D. Emotional exhaustion as a predictor of tinnitus. Psychother. Psychosom. 81, 324–326 (2012).

    PubMed  Google Scholar 

  12. Moller, A. R. Similarities between chronic pain and tinnitus. Am. J. Otol. 18, 577–585 (1997).

    CAS  PubMed  Google Scholar 

  13. Tonndorf, J. The analogy between tinnitus and pain: a suggestion for a physiological basis of chronic tinnitus. Hear. Res. 28, 271–275 (1987).

    CAS  PubMed  Google Scholar 

  14. De Ridder, D., Elgoyhen, A. B., Romo, R. & Langguth, B. Phantom percepts: tinnitus and pain as persisting aversive memory networks. Proc. Natl Acad. Sci. USA 108, 8075–8080 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. De Ridder, D., De Mulder, G., Menovsky, T., Sunaert, S. & Kovacs, S. Electrical stimulation of auditory and somatosensory cortices for treatment of tinnitus and pain. Prog. Brain Res. 166, 377–388 (2007).

    CAS  PubMed  Google Scholar 

  16. Hoare, D. J., Edmondson-Jones, M., Sereda, M., Akeroyd, M. A. & Hall, D. Amplification with hearing aids for patients with tinnitus and co-existing hearing loss. Cochrane Database Syst. Rev. 1, CD010151 (2014).

    Google Scholar 

  17. Hobson, J., Chisholm, E. & El Refaie, A. Sound therapy (masking) in the management of tinnitus in adults. Cochrane Database Syst. Rev. 11, CD006371 (2012).

    PubMed  Google Scholar 

  18. Baldo, P., Doree, C., Molin, P., McFerran, D. & Cecco, S. Antidepressants for patients with tinnitus. Cochrane Database Syst. Rev. 9, CD003853 (2012).

    Google Scholar 

  19. Hilton, M. P., Zimmermann, E. F. & Hunt, W. T. Ginkgo biloba for tinnitus. Cochrane Database Syst. Rev. 3, CD003852 (2013).

    Google Scholar 

  20. Hoekstra, C. E., Rynja, S. P., van Zanten, G. A. & Rovers, M. M. Anticonvulsants for tinnitus. Cochrane Database Syst. Rev. 7, CD007960 (2011).

    Google Scholar 

  21. Bennett, M. H., Kertesz, T., Perleth, M., Yeung, P. & Lehm, J. P. Hyperbaric oxygen for idiopathic sudden sensorineural hearing loss and tinnitus. Cochrane Database Syst. Rev. 10, CD004739 (2012).

    PubMed  Google Scholar 

  22. Park, J., White, A. R. & Ernst, E. Efficacy of acupuncture as a treatment for tinnitus: a systematic review. Arch. Otolaryngol. Head Neck Surg. 126, 489–492 (2000).

    CAS  PubMed  Google Scholar 

  23. Meng, Z., Liu, S., Zheng, Y. & Phillips, J. S. Repetitive transcranial magnetic stimulation for tinnitus. Cochrane Database Syst. Rev. 10, CD007946 (2011).

    Google Scholar 

  24. Hesser, H., Weise, C., Westin, V. Z. & Andersson, G. A systematic review and meta-analysis of randomized controlled trials of cognitive–behavioral therapy for tinnitus distress. Clin. Psychol. Rev. 31, 545–553 (2011).

    PubMed  Google Scholar 

  25. Tang, J., Ji, B. & Liu, L. [Study of hearing loss in 200 patients with subjective tinnitus]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 25, 726–729 (in Chinese) (2011).

    PubMed  Google Scholar 

  26. Kujawa, S. G. & Liberman, M. C. Adding insult to injury: cochlear nerve degeneration after “temporary” noise-induced hearing loss. J. Neurosci. 29, 14077–14085 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Weisz, N., Hartmann, T., Dohrmann, K., Schlee, W. & Norena, A. High-frequency tinnitus without hearing loss does not mean absence of deafferentation. Hear. Res. 222, 108–114 (2006).

    PubMed  Google Scholar 

  28. Eggermont, J. J. & Roberts, L. E. The neuroscience of tinnitus. Trends Neurosci. 27, 676–682 (2004).

    CAS  PubMed  Google Scholar 

  29. Rauschecker, J. P., Leaver, A. M. & Muhlau, M. Tuning out the noise: limbic–auditory interactions in tinnitus. Neuron 66, 819–826 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Norena, A. J. An integrative model of tinnitus based on a central gain controlling neural sensitivity. Neurosci. Biobehav. Rev. 35, 1089–1109 (2011).

    PubMed  Google Scholar 

  31. Roberts, L. E., Husain, F. T. & Eggermont, J. J. Role of attention in the generation and modulation of tinnitus. Neurosci. Biobehav. Rev. 37, 1754–1773 (2013).

    PubMed  Google Scholar 

  32. Eggermont, J. J. Hearing loss, hyperacusis, or tinnitus: what is modeled in animal research? Hear. Res. 295, 140–149 (2013).

    PubMed  Google Scholar 

  33. Llano, D. A., Turner, J. & Caspary, D. M. Diminished cortical inhibition in an aging mouse model of chronic tinnitus. J. Neurosci. 32, 16141–16148 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Schaette, R. & Kempter, R. Development of tinnitus-related neuronal hyperactivity through homeostatic plasticity after hearing loss: a computational model. Eur. J. Neurosci. 23, 3124–3138 (2006).

    PubMed  Google Scholar 

  35. Norena, A. J. & Eggermont, J. J. Changes in spontaneous neural activity immediately after an acoustic trauma: implications for neural correlates of tinnitus. Hear. Res. 183, 137–153 (2003).

    CAS  PubMed  Google Scholar 

  36. Basura, G. J., Koehler, S. D. & Shore, S. E. Multi-sensory integration in brainstem and auditory cortex. Brain Res. 1485, 95–107 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Kreuzer, P. M. et al. Trauma-associated tinnitus. J. Head Trauma Rehabil. 29, 432–442 (2014).

    PubMed  Google Scholar 

  38. Vielsmeier, V. et al. Temporomandibular joint disorder complaints in tinnitus: further hints for a putative tinnitus subtype. PLoS ONE 7, e38887 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Eggermont, J. J. & Komiya, H. Moderate noise trauma in juvenile cats results in profound cortical topographic map changes in adulthood. Hear. Res. 142, 89–101 (2000).

    CAS  PubMed  Google Scholar 

  40. Flores, E. N. et al. A non-canonical pathway from cochlea to brain signals tissue-damaging noise. Curr. Biol. 25, 606–612 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Rajan, R. Receptor organ damage causes loss of cortical surround inhibition without topographic map plasticity. Nat. Neurosci. 1, 138–143 (1998).

    CAS  PubMed  Google Scholar 

  42. Langers, D. R., de Kleine, E. & van Dijk, P. Tinnitus does not require macroscopic tonotopic map reorganization. Front. Syst. Neurosci. 6, 2 (2012).

    PubMed  PubMed Central  Google Scholar 

  43. Langers, D. R. Assessment of tonotopically organised subdivisions in human auditory cortex using volumetric and surface-based cortical alignments. Hum. Brain Mapp. 35, 1544–1561 (2013).

    PubMed  PubMed Central  Google Scholar 

  44. Yang, S., Weiner, B. D., Zhang, L. S., Cho, S. J. & Bao, S. Homeostatic plasticity drives tinnitus perception in an animal model. Proc. Natl Acad. Sci. USA 108, 14974–14979 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Roberts, L. E., Moffat, G., Baumann, M., Ward, L. M. & Bosnyak, D. J. Residual inhibition functions overlap tinnitus spectra and the region of auditory threshold shift. J. Assoc. Res. Otolaryngol. 9, 417–435 (2008).

    PubMed  PubMed Central  Google Scholar 

  46. Makin, T. R. et al. Phantom pain is associated with preserved structure and function in the former hand area. Nat. Commun. 4, 1570 (2013).

    PubMed  Google Scholar 

  47. Zheng, Y., Hamilton, E., McNamara, E., Smith, P. F. & Darlington, C. L. The effects of chronic tinnitus caused by acoustic trauma on social behaviour and anxiety in rats. Neuroscience 193, 143–153 (2011).

    CAS  PubMed  Google Scholar 

  48. Hayes, S. H., Radziwon, K. E., Stolzberg, D. J. & Salvi, R. J. Behavioral models of tinnitus and hyperacusis in animals. Front. Neurol. 5, 179 (2014).

    PubMed  PubMed Central  Google Scholar 

  49. Engineer, N. D. et al. Reversing pathological neural activity using targeted plasticity. Nature 470, 101–104 (2011).

    PubMed  PubMed Central  Google Scholar 

  50. De Ridder, D., Vanneste, S., Engineer, N. D. & Kilgard, M. P. Safety and efficacy of vagus nerve stimulation paired with tones for the treatment of tinnitus: a case series. Neuromodulation 17, 170–179 (2014).

    PubMed  Google Scholar 

  51. Zheng, Y., Hooton, K., Smith, P. F. & Darlington, C. L. Carbamazepine reduces the behavioural manifestations of tinnitus following salicylate treatment in rats. Acta Otolaryngol. 128, 48–52 (2008).

    CAS  PubMed  Google Scholar 

  52. Mardini, M. K. Ear-clicking “tinnitus” responding to carbamazepine. N. Engl. J. Med. 317, 1542 (1987).

    CAS  PubMed  Google Scholar 

  53. Norena, A. J. & Eggermont, J. J. Enriched acoustic environment after noise trauma abolishes neural signs of tinnitus. Neuroreport 17, 559–563 (2006).

    PubMed  Google Scholar 

  54. Vanneste, S. et al. Does enriched acoustic environment in humans abolish chronic tinnitus clinically and electrophysiologically? A double blind placebo controlled study. Hear. Res. 296, 141–148 (2013).

    PubMed  Google Scholar 

  55. Schecklmann, M., Landgrebe, M. & Langguth, B. Phenotypic characteristics of hyperacusis in tinnitus. PLoS ONE 9, e86944 (2014).

    PubMed  PubMed Central  Google Scholar 

  56. Fox, M. D. & Raichle, M. E. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat. Rev. Neurosci. 8, 700–711 (2007).

    CAS  PubMed  Google Scholar 

  57. Fornito, A. & Bullmore, E. T. What can spontaneous fluctuations of the blood oxygenation-level-dependent signal tell us about psychiatric disorders? Curr. Opin. Psychiatry 23, 239–249 (2010).

    PubMed  Google Scholar 

  58. Silchenko, A. N., Adamchic, I., Hauptmann, C. & Tass, P. A. Impact of acoustic coordinated reset neuromodulation on effective connectivity in a neural network of phantom sound. Neuroimage 77, 133–147 (2013).

    PubMed  Google Scholar 

  59. Vanneste, S., van de Heyning, P. & De Ridder, D. The neural network of phantom sound changes over time: a comparison between recent-onset and chronic tinnitus patients. Eur. J. Neurosci. 34, 718–731 (2011).

    PubMed  Google Scholar 

  60. Song, J. J., Vanneste, S., Schlee, W., Van de Heyning, P. & De Ridder, D. Onset-related differences in neural substrates of tinnitus-related distress: the anterior cingulate cortex in late-onset tinnitus, and the frontal cortex in early-onset tinnitus. Brain Struct. Funct. 220, 571–584 (2015).

    PubMed  Google Scholar 

  61. Aldhafeeri, F. M., Mackenzie, I., Kay, T., Alghamdi, J. & Sluming, V. Neuroanatomical correlates of tinnitus revealed by cortical thickness analysis and diffusion tensor imaging. Neuroradiology 54, 883–892 (2012).

    PubMed  Google Scholar 

  62. Job, A. et al. Abnormal cortical sensorimotor activity during “Target” sound detection in subjects with acute acoustic trauma sequelae: an fMRI study. Brain Behav. 2, 187–199 (2012).

    PubMed  PubMed Central  Google Scholar 

  63. Golm, D., Schmidt-Samoa, C., Dechent, P. & Kroner-Herwig, B. Neural correlates of tinnitus related distress: an fMRI-study. Hear. Res. 295, 87–99 (2013).

    PubMed  Google Scholar 

  64. Mirz, F., Gjedde, A., Ishizu, K. & Pedersen, C. B. Cortical networks subserving the perception of tinnitus — a PET study. Acta Otolaryngol. Suppl. 543, 241–243 (2000).

    CAS  PubMed  Google Scholar 

  65. Plewnia, C. et al. Dose-dependent attenuation of auditory phantom perception (tinnitus) by PET-guided repetitive transcranial magnetic stimulation. Hum. Brain Mapp. 28, 238–246 (2007).

    PubMed  Google Scholar 

  66. Schecklmann, M. et al. Neural correlates of tinnitus duration and distress: a positron emission tomography study. Hum. Brain Mapp. 34, 233–240 (2013).

    PubMed  Google Scholar 

  67. Song, J. J., De Ridder, D., Van de Heyning, P. & Vanneste, S. Mapping tinnitus-related brain activation: an activation-likelihood estimation metaanalysis of PET studies. J. Nucl. Med. 53, 1550–1557 (2012).

    PubMed  Google Scholar 

  68. Vanneste, S., Congedo, M. & De Ridder, D. Pinpointing a highly specific pathological functional connection that turns phantom sound into distress. Cereb. Cortex 24, 2268–2282 (2014).

    PubMed  Google Scholar 

  69. Vanneste, S. & De Ridder, D. Brain areas controlling heart rate variability in tinnitus and tinnitus-related distress. PLoS ONE 8, e59728 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Song, J. J., Punte, A. K., De Ridder, D., Vanneste, S. & Van de Heyning, P. Neural substrates predicting improvement of tinnitus after cochlear implantation in patients with single-sided deafness. Hear. Res. 299, 1–9 (2013).

    PubMed  Google Scholar 

  71. Adamchic, I., Hauptmann, C. & Tass, P. A. Changes of oscillatory activity in pitch processing network and related tinnitus relief induced by acoustic CR neuromodulation. Front. Syst. Neurosci. 6, 18 (2012).

    PubMed  PubMed Central  Google Scholar 

  72. Tass, P. A., Adamchic, I., Freund, H. J., von Stackelberg, T. & Hauptmann, C. Counteracting tinnitus by acoustic coordinated reset neuromodulation. Restor. Neurol. Neurosci. 30, 137–159 (2012).

    PubMed  Google Scholar 

  73. De Ridder, D., Vanneste, S. & Congedo, M. The distressed brain: a group blind source separation analysis on tinnitus. PLoS ONE 6, e24273 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Vanneste, S., Plazier, M., van der Loo, E., Van de Heyning, P. & De Ridder, D. The differences in brain activity between narrow band noise and pure tone tinnitus. PLoS ONE 5, e13618 (2010).

    PubMed  PubMed Central  Google Scholar 

  75. Moazami-Goudarzi, M., Michels, L., Weisz, N. & Jeanmonod, D. Temporo-insular enhancement of EEG low and high frequencies in patients with chronic tinnitus. QEEG study of chronic tinnitus patients. BMC Neurosci. 11, 40 (2010).

    PubMed  PubMed Central  Google Scholar 

  76. Vanneste, S. & De Ridder, D. Distress state dependent seed based functional connectivity on resting state EEG in tinnitus. Brain Connect. 5, 371–383 (2015).

    PubMed  Google Scholar 

  77. Lee, Y. J. et al. Evaluation of white matter structures in patients with tinnitus using diffusion tensor imaging. J. Clin. Neurosci. 14, 515–519 (2007).

    PubMed  Google Scholar 

  78. Andersson, G. et al. Regional cerebral blood flow during tinnitus: a PET case study with lidocaine and auditory stimulation. Acta Otolaryngol. 120, 967–972 (2000).

    CAS  PubMed  Google Scholar 

  79. Burton, H. et al. Altered networks in bothersome tinnitus: a functional connectivity study. BMC Neurosci. 13, 3 (2012).

    PubMed  PubMed Central  Google Scholar 

  80. Carpenter-Thompson, J. R., Akrofi, K., Schmidt, S. A., Dolcos, F. & Husain, F. T. Alterations of the emotional processing system may underlie preserved rapid reaction time in tinnitus. Brain Res. 1567, 28–41 (2014).

    CAS  PubMed  Google Scholar 

  81. Maudoux, A. et al. Auditory resting-state network connectivity in tinnitus: a functional MRI study. PLoS ONE 7, e36222 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Vanneste, S., Joos, K. & De Ridder, D. Prefrontal cortex based sex differences in tinnitus perception: same tinnitus intensity, same tinnitus distress, different mood. PLoS ONE 7, e31182 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Vanneste, S., Heyning, P. V. & Ridder, D. D. Contralateral parahippocampal gamma-band activity determines noise-like tinnitus laterality: a region of interest analysis. Neuroscience 199, 481–490 (2011).

    CAS  PubMed  Google Scholar 

  84. Vanneste, S., Plazier, M., van der Loo, E., Van de Heyning, P. & De Ridder, D. The difference between uni- and bilateral auditory phantom percept. Clin. Neurophysiol. 122, 578–587 (2011).

    PubMed  Google Scholar 

  85. Vanneste, S. et al. The neural correlates of tinnitus-related distress. Neuroimage 52, 470–480 (2010).

    PubMed  Google Scholar 

  86. Kim, J. Y. et al. Alteration of functional connectivity in tinnitus brain revealed by resting-state fMRI? A pilot study. Int. J. Audiol. 51, 413–417 (2012).

    PubMed  Google Scholar 

  87. Schecklmann, M. et al. Auditory cortex is implicated in tinnitus distress: a voxel-based morphometry study. Brain Struct. Funct. 218, 1061–1070 (2013).

    CAS  PubMed  Google Scholar 

  88. Lehner, A. et al. Structural brain changes following left temporal low-frequency rTMS in patients with subjective tinnitus. Neural Plast. 2014, 132058 (2014).

    PubMed  PubMed Central  Google Scholar 

  89. van der Loo, E., Congedo, M., Vanneste, S., Van De Heyning, P. & De Ridder, D. Insular lateralization in tinnitus distress. Auton. Neurosci. 165, 191–194 (2011).

    CAS  PubMed  Google Scholar 

  90. De Ridder, D. et al. An integrative model of auditory phantom perception: tinnitus as a unified percept of interacting separable subnetworks. Neurosci. Biobehav. Rev. 44, 16–32 (2014).

    PubMed  Google Scholar 

  91. Hoekstra, C. E., Wesdorp, F. M. & van Zanten, G. A. Socio-demographic, health, and tinnitus related variables affecting tinnitus severity. Ear Hear. 35, 544–554 (2014).

    PubMed  Google Scholar 

  92. Landgrebe, M. et al. Methodological aspects of clinical trials in tinnitus: a proposal for an international standard. J. Psychosom. Res. 73, 112–121 (2012).

    PubMed  PubMed Central  Google Scholar 

  93. Schneider, P. et al. Reduced volume of Heschl's gyrus in tinnitus. Neuroimage 45, 927–939 (2009).

    PubMed  Google Scholar 

  94. Boyen, K., Langers, D. R., de Kleine, E. & van Dijk, P. Gray matter in the brain: differences associated with tinnitus and hearing loss. Hear. Res. 295, 67–78 (2013).

    PubMed  Google Scholar 

  95. Landgrebe, M. et al. Structural brain changes in tinnitus: grey matter decrease in auditory and non-auditory brain areas. Neuroimage 46, 213–218 (2009).

    PubMed  Google Scholar 

  96. Muhlau, M. et al. Structural brain changes in tinnitus. Cereb. Cortex 16, 1283–1288 (2006).

    CAS  PubMed  Google Scholar 

  97. Leaver, A. M. et al. Dysregulation of limbic and auditory networks in tinnitus. Neuron 69, 33–43 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Mahoney, C. J. et al. Structural neuroanatomy of tinnitus and hyperacusis in semantic dementia. J. Neurol. Neurosurg. Psychiatry 82, 1274–1278 (2011).

    PubMed  Google Scholar 

  99. Diesch, E., Schummer, V., Kramer, M. & Rupp, A. Structural changes of the corpus callosum in tinnitus. Front. Syst. Neurosci. 6, 17 (2012).

    PubMed  PubMed Central  Google Scholar 

  100. Leaver, A. M. et al. Cortico-limbic morphology separates tinnitus from tinnitus distress. Front. Syst. Neurosci. 6, 21 (2012).

    PubMed  PubMed Central  Google Scholar 

  101. Husain, F. T. et al. Neuroanatomical changes due to hearing loss and chronic tinnitus: a combined VBM and DTI study. Brain Res. 1369, 74–88 (2011).

    CAS  PubMed  Google Scholar 

  102. Melcher, J. R., Knudson, I. M. & Levine, R. A. Subcallosal brain structure: correlation with hearing threshold at supra-clinical frequencies (>8 kHz), but not with tinnitus. Hear. Res. 295, 79–86 (2013).

    PubMed  Google Scholar 

  103. Lockwood, A. H. et al. The functional anatomy of gaze-evoked tinnitus and sustained lateral gaze. Neurology 56, 472–480 (2001).

    CAS  PubMed  Google Scholar 

  104. Lanting, C. P., de Kleine, E., Eppinga, R. N. & van Dijk, P. Neural correlates of human somatosensory integration in tinnitus. Hear. Res. 267, 78–88 (2010).

    CAS  PubMed  Google Scholar 

  105. Reyes, S. A. et al. Brain imaging of the effects of lidocaine on tinnitus. Hear. Res. 171, 43–50 (2002).

    CAS  PubMed  Google Scholar 

  106. Marcondes, R. A. et al. Repetitive transcranial magnetic stimulation improve tinnitus in normal hearing patients: a double-blind controlled, clinical and neuroimaging outcome study. Eur. J. Neurol. 17, 38–44 (2010).

    CAS  PubMed  Google Scholar 

  107. De Ridder, D. et al. Burst stimulation of the auditory cortex: a new form of neurostimulation for noise-like tinnitus suppression. J. Neurosurg. 112, 1289–1294 (2010).

    PubMed  Google Scholar 

  108. Vanneste, S. & De Ridder, D. The auditory and non-auditory brain areas involved in tinnitus. An emergent property of multiple parallel overlapping subnetworks. Front. Syst. Neurosci. 6, 31 (2012).

    PubMed  PubMed Central  Google Scholar 

  109. Schlee, W., Hartmann, T., Langguth, B. & Weisz, N. Abnormal resting-state cortical coupling in chronic tinnitus. BMC Neurosci. 10, 11 (2009).

    PubMed  PubMed Central  Google Scholar 

  110. Adamchic, I., Toth, T., Hauptmann, C. & Tass, P. A. Reversing pathologically increased EEG power by acoustic coordinated reset neuromodulation. Hum. Brain Mapp. 35, 2099–2118 (2014).

    PubMed  Google Scholar 

  111. van der Loo, E. et al. Tinnitus intensity dependent gamma oscillations of the contralateral auditory cortex. PLoS ONE 4, e7396 (2009).

    PubMed  PubMed Central  Google Scholar 

  112. Llinas, R. R., Ribary, U., Jeanmonod, D., Kronberg, E. & Mitra, P. P. Thalamocortical dysrhythmia: a neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc. Natl Acad. Sci. USA 96, 15222–15227 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Weisz, N. et al. The neural code of auditory phantom perception. J. Neurosci. 27, 1479–1484 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Smits, M. et al. Lateralization of functional magnetic resonance imaging (fMRI) activation in the auditory pathway of patients with lateralized tinnitus. Neuroradiology 49, 669–679 (2007).

    PubMed  Google Scholar 

  115. Zobay, O., Palmer, A. R., Hall, D. A., Sereda, M. & Adjamian, P. Source space estimation of oscillatory power and brain connectivity in tinnitus. PLoS ONE 10, e0120123 (2015).

    PubMed  PubMed Central  Google Scholar 

  116. Llinas, R., Urbano, F. J., Leznik, E., Ramirez, R. R. & van Marle, H. J. Rhythmic and dysrhythmic thalamocortical dynamics: GABA systems and the edge effect. Trends Neurosci. 28, 325–333 (2005).

    CAS  PubMed  Google Scholar 

  117. Kaiser, J. & Lutzenberger, W. Human gamma-band activity: a window to cognitive processing. Neuroreport 16, 207–211 (2005).

    PubMed  Google Scholar 

  118. Potes, C., Brunner, P., Gunduz, A., Knight, R. T. & Schalk, G. Spatial and temporal relationships of electrocorticographic alpha and gamma activity during auditory processing. Neuroimage 97, 188–195 (2014).

    PubMed  Google Scholar 

  119. Canolty, R. T. et al. High gamma power is phase-locked to theta oscillations in human neocortex. Science 313, 1626–1628 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Doesburg, S. M., Green, J. J., McDonald, J. J. & Ward, L. M. Theta modulation of inter-regional gamma synchronization during auditory attention control. Brain Res. 1431, 77–85 (2012).

    CAS  PubMed  Google Scholar 

  121. Sametsky, E. A., Turner, J. G., Larsen, D., Ling, L. & Caspary, D. M. Enhanced GABAA-mediated tonic inhibition in auditory thalamus of rats with behavioral evidence of tinnitus. J. Neurosci. 35, 9369–9380 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. De Ridder, D., Vanneste, S., Langguth, B. & Llinas, R. Thalamocortical dysrhythmia: a theoretical update in tinnitus. Front. Neurol. 6, 124 (2015).

    PubMed  PubMed Central  Google Scholar 

  123. Muller, N., Lorenz, I., Langguth, B. & Weisz, N. rTMS induced tinnitus relief is related to an increase in auditory cortical alpha activity. PLoS ONE 8, e55557 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Sedley, W. et al. Single-subject oscillatory gamma responses in tinnitus. Brain 135, 3089–3100 (2012).

    PubMed  PubMed Central  Google Scholar 

  125. Vanneste, S., Song, J. J. & De Ridder, D. Tinnitus and musical hallucinosis: the same but more. Neuroimage 82, 373–383 (2013).

    PubMed  Google Scholar 

  126. Ortmann, M., Muller, N., Schlee, W. & Weisz, N. Rapid increases of gamma power in the auditory cortex following noise trauma in humans. Eur. J. Neurosci. 33, 568–575 (2011).

    PubMed  Google Scholar 

  127. Kahlbrock, N. & Weisz, N. Transient reduction of tinnitus intensity is marked by concomitant reductions of delta band power. BMC Biol. 6, 4 (2008).

    PubMed  PubMed Central  Google Scholar 

  128. Lockwood, A. H. et al. The functional neuroanatomy of tinnitus: evidence for limbic system links and neural plasticity. Neurology 50, 114–120 (1998).

    CAS  PubMed  Google Scholar 

  129. Arnold, W., Bartenstein, P., Oestreicher, E., Romer, W. & Schwaiger, M. Focal metabolic activation in the predominant left auditory cortex in patients suffering from tinnitus: a PET study with [18F]deoxyglucose. ORL J. Otorhinolaryngol. Relat. Spec. 58, 195–199 (1996).

    CAS  PubMed  Google Scholar 

  130. Giraud, A. L. et al. A selective imaging of tinnitus. Neuroreport 10, 1–5 (1999).

    CAS  PubMed  Google Scholar 

  131. Boyen, K., de Kleine, E., van Dijk, P. & Langers, D. R. Tinnitus-related dissociation between cortical and subcortical neural activity in humans with mild to moderate sensorineural hearing loss. Hear. Res. 312, 48–59 (2014).

    PubMed  Google Scholar 

  132. Schlee, W. et al. Mapping cortical hubs in tinnitus. BMC Biol. 7, 80 (2009).

    PubMed  PubMed Central  Google Scholar 

  133. Schlee, W., Weisz, N., Bertrand, O., Hartmann, T. & Elbert, T. Using auditory steady state responses to outline the functional connectivity in the tinnitus brain. PLoS ONE 3, e3720 (2008).

    PubMed  PubMed Central  Google Scholar 

  134. de Lafuente, V. & Romo, R. Neuronal correlates of subjective sensory experience. Nat. Neurosci. 8, 1698–1703 (2005).

    CAS  PubMed  Google Scholar 

  135. Steinmann, S. et al. Conscious auditory perception related to long-range synchrony of gamma oscillations. Neuroimage 100, 435–443 (2014).

    PubMed  Google Scholar 

  136. Boly, M. et al. Auditory processing in severely brain injured patients: differences between the minimally conscious state and the persistent vegetative state. Arch. Neurol. 61, 233–238 (2004).

    PubMed  Google Scholar 

  137. Laureys, S. et al. Auditory processing in the vegetative state. Brain 123, 1589–1601 (2000).

    PubMed  Google Scholar 

  138. Sadaghiani, S., Hesselmann, G. & Kleinschmidt, A. Distributed and antagonistic contributions of ongoing activity fluctuations to auditory stimulus detection. J. Neurosci. 29, 13410–13417 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Seydell-Greenwald, A. et al. Functional MRI evidence for a role of ventral prefrontal cortex in tinnitus. Brain Res. 1485, 22–39 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Fields, H. State-dependent opioid control of pain. Nat. Rev. Neurosci. 5, 565–575 (2004).

    CAS  PubMed  Google Scholar 

  141. Kong, J. et al. Exploring the brain in pain: activations, deactivations and their relation. Pain 148, 257–267 (2010).

    PubMed  Google Scholar 

  142. Vanneste, S., Joos, K., Langguth, B., To, W. T. & De Ridder, D. Neuronal correlates of maladaptive coping: an EEG-study in tinnitus patients. PLoS ONE 9, e88253 (2014).

    PubMed  PubMed Central  Google Scholar 

  143. Maudoux, A. et al. Connectivity graph analysis of the auditory resting state network in tinnitus. Brain Res. 1485, 10–21 (2012).

    CAS  PubMed  Google Scholar 

  144. De Ridder, D. et al. Amygdalohippocampal involvement in tinnitus and auditory memory. Acta Otolaryngol. Suppl. 556, 50–53 (2006).

    Google Scholar 

  145. Menon, V. & Uddin, L. Q. Saliency, switching, attention and control: a network model of insula function. Brain Struct. Funct. 214, 655–667 (2010).

    PubMed  PubMed Central  Google Scholar 

  146. Deco, G., Jirsa, V. K. & McIntosh, A. R. Emerging concepts for the dynamical organization of resting-state activity in the brain. Nat. Rev. Neurosci. 12, 43–56 (2011).

    CAS  PubMed  Google Scholar 

  147. Raichle, M. E. et al. A default mode of brain function. Proc. Natl Acad. Sci. USA 98, 676–682 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Vincent, J. L., Kahn, I., Snyder, A. Z., Raichle, M. E. & Buckner, R. L. Evidence for a frontoparietal control system revealed by intrinsic functional connectivity. J. Neurophysiol. 100, 3328–3342 (2008).

    PubMed  PubMed Central  Google Scholar 

  149. Seeley, W. W. et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J. Neurosci. 27, 2349–2356 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Dalgleish, T. The emotional brain. Nat. Rev. Neurosci. 5, 583–589 (2004).

    PubMed  Google Scholar 

  151. Adjamian, P., Sereda, M. & Hall, D. A. The mechanisms of tinnitus: perspectives from human functional neuroimaging. Hear. Res. 253, 15–31 (2009).

    PubMed  Google Scholar 

  152. Adjamian, P., Hall, D. A., Palmer, A. R., Allan, T. W. & Langers, D. R. Neuroanatomical abnormalities in chronic tinnitus in the human brain. Neurosci. Biobehav. Rev. 45, 119–133 (2014).

    PubMed  PubMed Central  Google Scholar 

  153. Ruhnau, P., Hauswald, A. & Weisz, N. Investigating ongoing brain oscillations and their influence on conscious perception — network states and the window to consciousness. Front. Psychol. 5, 1230 (2014).

    PubMed  PubMed Central  Google Scholar 

  154. Knudson, I. M., Shera, C. A. & Melcher, J. R. Increased contralateral suppression of otoacoustic emissions indicates a hyperresponsive medial olivocochlear system in humans with tinnitus and hyperacusis. J. Neurophysiol. 112, 3197–3208 (2014).

    PubMed  PubMed Central  Google Scholar 

  155. Schecklmann, M. et al. Cluster analysis for identifying sub-types of tinnitus: a positron emission tomography and voxel-based morphometry study. Brain Res. 1485, 3–9 (2012).

    CAS  PubMed  Google Scholar 

  156. Elgoyhen, A. B. et al. Identifying tinnitus-related genes based on a side-effect network analysis. CPT Pharmacometrics Syst. Pharmacol. 3, e97 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. De Ridder, D. & Vanneste, S. Auditory cortex stimulation might be efficacious in a subgroup of tinnitus patients. Brain Stimul. 7, 917–918 (2014).

    PubMed  Google Scholar 

  158. Langguth, B. et al. Neuroimaging and neuromodulation: complementary approaches for identifying the neuronal correlates of tinnitus. Front. Syst. Neurosci. 6, 15 (2012).

    PubMed  PubMed Central  Google Scholar 

  159. Bullmore, E. & Sporns, O. Complex brain networks: graph theoretical analysis of structural and functional systems. Nat. Rev. Neurosci. 10, 186–198 (2009).

    CAS  PubMed  Google Scholar 

  160. Bullmore, E. T. & Bassett, D. S. Brain graphs: graphical models of the human brain connectome. Annu. Rev. Clin. Psychol. 7, 113–140 (2011).

    PubMed  Google Scholar 

  161. Turner, J. G. Behavioral measures of tinnitus in laboratory animals. Prog. Brain Res. 166, 147–156 (2007).

    PubMed  Google Scholar 

  162. Jastreboff, P. J., Brennan, J. F., Coleman, J. K. & Sasaki, C. T. Phantom auditory sensation in rats: an animal model for tinnitus. Behav. Neurosci. 102, 811–822 (1988).

    CAS  PubMed  Google Scholar 

  163. Lanting, C. P., De Kleine, E., Bartels, H. & Van Dijk, P. Functional imaging of unilateral tinnitus using fMRI. Acta Otolaryngol. 128, 415–421 (2008).

    CAS  PubMed  Google Scholar 

  164. Melcher, J. R., Sigalovsky, I. S., Guinan, J. J. Jr & Levine, R. A. Lateralized tinnitus studied with functional magnetic resonance imaging: abnormal inferior colliculus activation. J. Neurophysiol. 83, 1058–1072 (2000).

    CAS  PubMed  Google Scholar 

  165. Melcher, J. R., Levine, R. A., Bergevin, C. & Norris, B. The auditory midbrain of people with tinnitus: abnormal sound-evoked activity revisited. Hear. Res. 257, 63–74 (2009).

    PubMed  PubMed Central  Google Scholar 

  166. Gu, J. W., Halpin, C. F., Nam, E. C., Levine, R. A. & Melcher, J. R. Tinnitus, diminished sound-level tolerance, and elevated auditory activity in humans with clinically normal hearing sensitivity. J. Neurophysiol. 104, 3361–3370 (2010).

    PubMed  PubMed Central  Google Scholar 

  167. Langers, D. R. & Melcher, J. R. Hearing without listening: functional connectivity reveals the engagement of multiple nonauditory networks during basic sound processing. Brain Connect. 1, 233–244 (2011).

    PubMed  PubMed Central  Google Scholar 

  168. Lanting, C. P., de Kleine, E., Langers, D. R. & van Dijk, P. Unilateral tinnitus: changes in connectivity and response lateralization measured with fMRI. PLoS ONE 9, e110704 (2014).

    PubMed  PubMed Central  Google Scholar 

  169. Hudspeth, A. How hearing happens. Neuron 19, 947–950 (1997).

    CAS  PubMed  Google Scholar 

  170. Smith, P. & Spirou, G. in Integrative Functions in the Mammalian Auditory Pathway (eds Oertel, D., Fay, R. & Oertel, A.) 6–71 (Springer, 2002).

    Google Scholar 

  171. Moller, A. R. & Rollins, P. R. The non-classical auditory pathways are involved in hearing in children but not in adults. Neurosci. Lett. 319, 41–44 (2002).

    CAS  PubMed  Google Scholar 

  172. Liberman, L. D. & Liberman, M. C. Dynamics of cochlear synaptopathy after acoustic overexposure. J. Assoc. Res. Otolaryngol. 16, 205–219 (2015).

    PubMed  PubMed Central  Google Scholar 

  173. Bauer, C. A., Turner, J. G., Caspary, D. M., Myers, K. S. & Brozoski, T. J. Tinnitus and inferior colliculus activity in chinchillas related to three distinct patterns of cochlear trauma. J. Neurosci. Res. 86, 2564–2578 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Crippa, A., Lanting, C. P., van Dijk, P. & Roerdink, J. B. A diffusion tensor imaging study on the auditory system and tinnitus. Open Neuroimag. J. 4, 16–25 (2010).

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors are supported in part by the Tinnitus Research Initiative.

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Correspondence to Ana Belén Elgoyhen.

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Competing interests

A.B.E. has received research funding from Merz. B.L. received honoraria for speaking and consultancy from Advanced Neuro Modulation, AstraZeneca, Autifony, Gerson Lehrman Group, Lundbeck, McKinsey, Merz, Magventure, Novartis, Neuromod Devices, Pfizer and Servier; received research funding from AstraZeneca, Cerbomed, Deymed, Magventure, Siemens and Otonomy; received travel and accommodation payments from the European Union (European Cooperation in Science and Technology (COST)), Lilly, Servier and Pfizer; and holds patents for the use of neuronavigation for transcranial magnetic stimulation in the treatment of tinnitus. D.D.R. has received speaker's fees, travel and accommodation payments and research funding from St Jude Medical and holds intellectual property rights to different neurostimulation designs for implanted electrodes. A.B.E., B.L. and D.D.R. hold a patent for the use of cyclobenzaprine in tinnitus treatment. S.V. declares no competing interests.

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Elgoyhen, A., Langguth, B., De Ridder, D. et al. Tinnitus: perspectives from human neuroimaging. Nat Rev Neurosci 16, 632–642 (2015). https://doi.org/10.1038/nrn4003

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