An overview of the tinnitus network activity and its clinical implications

  • Samer Mohsen Department of Audiology, School of Rehabilitation Sciences, International Campus, Iran University of Medical Sciences, Tehran, Iran AND Department of Otolaryngology, School of Medicine, Damascus University, Damascus, Syria
  • Akram Pourbakht Department of Audiology, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran
Keywords: Tinnitus, tinnitus network, distress network, attention network, functional connectivity


Background and Aim: Tinnitus, the phantom perception of sound, in which many cortical and subcortical areas are involved has become one of the popular subjects of neuroscience research. Neuroimaging studies have introduced the tinnitus network model to explain the involvement of auditory and non-auditory areas in this perception. In such a model, the cognitive and emotional aspects of tinnitus can be interpreted conveniently. Therefore, this paper aimed to review the neural basis of tinnitus networks, including data from neuroimaging studies, and discuss the clinical implication of this concept, as well.Recent Findings: The data from neuroimaging studies were reviewed and discussed in order to complete the overall image of tinnitus network and its correlates such as the distress network, attentional network and other cognitive mechanisms. In addition to the auditory system, the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) were considered to be important hubs in tinnitus distress network, especially for having important connectivity with the other networks like attention and salience networks. Moreover, the top-down control of DLPFC over the other brain areas was regarded as the most important brain area to be targeted using the non-invasive interventions and the results were compelling.Conclusion: Understanding the network model has helped in optimizing the neuromodulatison protocols like electrical stimulation techniques. Thus, the clinical implications of this model can be generalized to the other types of treatments and the outcomes might be satisfying.


1. Jastreboff PJ. Phantom auditory perception (tinnitus): mechanisms of generation and perception. Neurosci Res. 1990;8(4):221-54. doi: 10.1016/0168-0102(90)90031-9
2. Eggermont JJ. Central tinnitus. Auris Nasus Larynx. 2003;30 Suppl:S7-12. doi: 10.1016/S0385-8146(02)00122-0
3. Heller AJ. Classification and epidemiology of tinnitus. Otolaryngol Clin North Am. 2003;36(2):239-48. doi: 10.1016/S0030-6665(02)00160-3
4. Bhatt JM, Lin HW, Bhattacharyya N. Prevalence, severity, exposures, and treatment patterns of tinnitus in the United States. JAMA Otolaryngol Head Neck Surg. 2016;142(10):959-65. doi: 10.1001/jamaoto.2016.1700
5. Alster J, Shemesh Z, Ornan M, Attias J. Sleep disturbance associated with chronic tinnitus. Biol Psychiatry. 1993;34(1-2):84-90. doi: 10.1016/0006-3223(93)90260-K
6. Carlsson SG, Erlandsson SI. Habituation and tinnitus: an experimental study. J Psychosom Res. 1991;35(4-5):509-14. doi: 10.1016/0022-3999(91)90045-P
7. Landgrebe M, Azevedo A, Baguley D, Bauer C, Cacace A, Coelho C, et al. Methodological aspects of clinical trials in tinnitus: a proposal for an international standard. J Psychosom Res. 2012;73(2):112-21. doi: 10.1016/j.jpsychores.2012.05.002
8. De Ridder D, Vanneste S, Freeman W. The Bayesian brain: phantom percepts resolve sensory uncertainty. Neurosci Biobehav Rev. 2014;44:4-15. doi: 10.1016/j.neubiorev.2012.04.001
9. Roberts LE. Neural plasticity and its initiating conditions in tinnitus. HNO. 2018;66(3):172-8. doi: 10.1007/s00106-017-0449-2
10. Eggermont JJ. Cortical tonotopic map reorganization and its implications for treatment of tinnitus. Acta Otolaryngol Suppl. 2006;(556):9-12. doi: 10.1080/03655230600895259
11. Shore SE, Roberts LE, Langguth B. Maladaptive plasticity in tinnitus--triggers, mechanisms and treatment. Nat Rev Neurol. 2016;12(3):150-60. doi: 10.1038/nrneurol.2016.12
12. Geven LI, Köppl C, de Kleine E, van Dijk P. Plasticity in tinnitus patients: a role for the efferent auditory system? Otol Neurotol. 2014;35(5):796-802. doi: 10.1097/MAO.0000000000000307
13. Schlee W, Hartmann T, Langguth B, Weisz N. Abnormal resting-state cortical coupling in chronic tinnitus. BMC Neurosci. 2009;10:11. doi: 10.1186/1471-2202-10-11
14. 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. 2012;6:31. doi: 10.3389/fnsys.2012.00031
15. Adamchic I, Langguth B, Hauptmann C, Tass PA. Abnormal cross-frequency coupling in the tinnitus network. Front Neurosci. 2014;8:284. doi: 10.3389/fnins.2014.00284
16. De Ridder D, Vanneste S, Weisz N, Londero A, Schlee W, Elgoyhen AB, et al. An integrative model of auditory phantom perception: tinnitus as a unified percept of interacting separable subnetworks. Neurosci Biobehav Rev. 2014;44:16-32. doi: 10.1016/j.neubiorev.2013.03.021
17. Husain FT. Neural networks of tinnitus in humans: Elucidating severity and habituation. Hear Res. 2016;334:37-48. doi: 10.1016/j.heares.2015.09.010
18. Pessoa L. The cognitive-emotional brain: from interactions to integration. Cambridge: The MIT Press; 2013.
19. Young MP, Scannell JW, Burns GA, Blakemore C. Analysis of connectivity: neural systems in the cerebral cortex. Rev Neurosci. 1994;5(3):227-50.
20. Pessoa L. Understanding brain networks and brain organization. Phys Life Rev. 2014;11(3):400-35. doi: 10.1016/j.plrev.2014.03.005
21. Park HJ, Friston K. Structural and functional brain networks: from connections to cognition. Science. 2013;342(6158):1238411. doi: 10.1126/science.1238411
22. Sporns O, Honey CJ, Kötter R. Identification and classification of hubs in brain networks. PLoS One. 2007;2(10):e1049. doi: 10.1371/journal.pone.0001049
23. Husain FT, Schmidt SA. Using resting state functional connectivity to unravel networks of tinnitus. Hear Res. 2014;307:153-62. doi: 10.1016/j.heares.2013.07.010
24. De Ridder D, Vanneste S, Congedo M. The distressed brain: a group blind source separation analysis
on tinnitus. PLoS One. 2011;6(10):e24273. doi: 10.1371/journal.pone.0024273
25. Paus T, Castro-Alamancos MA, Petrides M. Cortico-cortical connectivity of the human mid-dorsolateral frontal cortex and its modulation by repetitive transcranial magnetic stimulation. Eur J Neurosci. 2001;14(8):1405-11. doi: 10.1046/j.0953-816x.2001.01757.x
26. Johnson JA, Strafella AP, Zatorre RJ. The role of the dorsolateral prefrontal cortex in bimodal divided attention: two transcranial magnetic stimulation studies. J Cogn Neurosci. 2007;19(6):907-20. doi: 10.1162/jocn.2007.19.6.907
27. Noreña AJ, Farley BJ. Tinnitus-related neural activity: theories of generation, propagation, and centralization. Hear Res. 2013;295:161-71. doi: 10.1016/j.heares.2012.09.010
28. Lorenz I, Müller N, Schlee W, Hartmann T, Weisz N. Loss of alpha power is related to increased gamma synchronization-A marker of reduced inhibition in tinnitus? Neurosci Lett. 2009;453(3):225-8. doi: 10.1016/j.neulet.2009.02.028
29. 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. 2010;11:40. doi: 10.1186/1471-2202-11-40
30. Meyer M, Luethi MS, Neff P, Langer N, Büchi S. Disentangling tinnitus distress and tinnitus presence by means of EEG power analysis. Neural Plast. 2014;2014:468546. doi: 10.1155/2014/468546
31. Simonetti P, Oiticica J. Tinnitus neural mechanisms and structural changes in the brain: the contribution of neuroimaging research. Int Arch Otorhinolaryngol. 2015;19(3):259-65. doi: 10.1055/s-0035-1548671
32. De Ridder D, Vanneste S, Langguth B, Llinas R. Thalamocortical dysrhythmia: a theoretical update in tinnitus. Front Neurol. 2015;6:124. doi: 10.3389/fneur.2015.00124
33. Weisz N, Moratti S, Meinzer M, Dohrmann K, Elbert T. Tinnitus perception and distress is related to abnormal spontaneous brain activity as measured by magnetoencephalography. PLoS Med. 2005;2(6):e153. doi: 10.1371/journal.pmed.0020153
34. Schlee W, Schecklmann M, Lehner A, Kreuzer PM, Vielsmeier V, Poeppl TB, et al. Reduced variability of auditory alpha activity in chronic tinnitus. Neural Plast. 2014;2014:436146. doi: 10.1155/2014/436146
35. Llinás RR, Ribary U, Jeanmonod D, Kronberg E, Mitra PP. Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci U S A. 1999;96(26):15222-7.
36. De Ridder D, Elgoyhen AB, Romo R, Langguth B. Phantom percepts: tinnitus and pain as persisting aversive memory networks. Proc Natl Acad Sci U S A. 2011;108(20):8075-80. doi: 10.1073/pnas.1018466108
37. Roberts LE, Husain FT, Eggermont JJ. Role of attention in the generation and modulation of tinnitus. Neurosci Biobehav Rev. 2013;37(8):1754-73. doi: 10.1016/j.neubiorev.2013.07.007
38. Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A. 2005;102(27):9673-8. doi: 10.1073/pnas.0504136102
39. Schmidt SA, Akrofi K, Carpenter-Thompson JR, Husain FT. Default mode, dorsal attention and auditory resting state networks exhibit differential functional connectivity in tinnitus and hearing loss. PLoS One. 2013;8(10):e76488. doi: 10.1371/journal.pone.0076488
40. Vanneste S, Plazier M, der Loo Ev, de Heyning PV, Congedo M, De Ridder D. The neural correlates of tinnitus-related distress. Neuroimage. 2010;52(2):470-80. doi: 10.1016/j.neuroimage.2010.04.029
41. Chen YC, Bo F, Xia W, Liu S, Wang P, Su W, et al. Amygdala functional disconnection with the prefrontal-cingulate-temporal circuit in chronic tinnitus patients with depressive mood. Prog Neuropsychopharmacol Biol Psychiatry. 2017;79(Pt B):249-57. doi: 10.1016/j.pnpbp.2017.07.001
42. Vanneste S, Joos K, Ost J, De Ridder D. Influencing connectivity and cross-frequency coupling by real-time source localized neurofeedback of the posterior cingulate cortex reduces tinnitus related distress. Neurobiol Stress. 2016;8:211-24. doi: 10.1016/j.ynstr.2016.11.003
43. van der Loo E, Congedo M, Vanneste S, Van De Heyning P, De Ridder D. Insular lateralization in tinnitus distress. Auton Neurosci. 2011;165(2):191-4. doi: 10.1016/j.autneu.2011.06.007
44. De Ridder D, Fransen H, Francois O, Sunaert S, Kovacs S, Van De Heyning P. Amygdalohippocampal involvement in tinnitus and auditory memory. Acta Otolaryngol Suppl. 2006;(556):50-3. doi: 10.1080/03655230600895580
45. De Ridder D. Phantom perceptions: The analogy between pain and tinnitus. Neuroscience Letters. 2011;500(Supplement):e2. doi: 10.1016/j.neulet.2011.05.064
46. Schlee W, Mueller N, Hartmann T, Keil J, Lorenz I, Weisz N. Mapping cortical hubs in tinnitus. BMC Biol. 2009;7:80. doi: 10.1186/1741-7007-7-80
47. Schmidt SA, Carpenter-Thompson J, Husain FT. Connectivity of precuneus to the default mode and dorsal attention networks: A possible invariant marker of long-term tinnitus. Neuroimage Clin. 2017;16:196-204. doi: 10.1016/j.nicl.2017.07.015
48. Joos K, Vanneste S, De Ridder D. Disentangling depression and distress networks in the tinnitus brain. PLoS One. 2012;7(7):e40544. doi: 10.1371/journal.pone.0040544
49. Boggio PS, Zaghi S, Fregni F. Modulation of emotions associated with images of human pain using anodal transcranial direct current stimulation (tDCS). Neuropsychologia. 2009;47(1):212-7. doi: 10.1016/j.neuropsychologia.2008.07.022
50. Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science. 2000;288(5472):1769-72.
51. Begić D, Hotujac L, Jokić-Begić N. Electroencephalographic comparison of veterans with combat-related post-traumatic stress disorder and healthy subjects. Int J Psychophysiol. 2001;40(2):167-72. doi: 10.1016/S0167-8760(00)00153-7
52. Ito SI. Prefrontal unit activity of macaque monkeys during auditory and visual reaction time tasks. Brain Res. 1982;247(1):39-47. doi: 10.1016/0006-8993(82)91025-3
53. Plakke B, Romanski LM. Auditory connections and functions of prefrontal cortex. Front Neurosci. 2014;8:199. doi: 10.3389/fnins.2014.00199
54. Arnott SR, Grady CL, Hevenor SJ, Graham S, Alain C. The functional organization of auditory working memory as revealed by fMRI. J Cogn Neurosci. 2005;17(5):819-31. doi: 10.1162/0898929053747612
55. Plakke B, Ng CW, Poremba A. Neural correlates of auditory recognition memory in primate lateral prefrontal cortex. Neuroscience. 2013;244:62-76. doi: 10.1016/j.neuroscience.2013.04.002
56. Araneda R, Renier L, Dricot L, Decat M, Ebner-Karestinos D, Deggouj N, et al. A key role of the prefrontal cortex in the maintenance of chronic tinnitus: An fMRI study using a Stroop task. Neuroimage Clin. 2017;17:325-34. doi: 10.1016/j.nicl.2017.10.029
57. Mohsen S, Mahmoudian S, Talebian S, Pourbakht A. Correlation analysis of the tinnitus handicap inventory and distress network activity in chronic tinnitus: an EEG study. Basic and Clinical Neuroscience. 2018;accepted manuscript. In press.
58. De Ridder D, Vanneste S, Plazier M, Menovsky T, van de Heyning P, Kovacs S, et al. Dorsolateral prefrontal cortex transcranial magnetic stimulation and electrode implant for intractable tinnitus. World Neurosurg. 2012;77(5-6):778-84. doi: 10.1016/j.wneu.2011.09.009
59. Vanneste S, Faber M, Langguth B, De Ridder D. The neural correlates of cognitive dysfunction in phantom sounds. Brain Res. 2016;1642:170-9. doi: 10.1016/j.brainres.2016.03.016
60. Critchley HD, Corfield DR, Chandler MP, Mathias CJ, Dolan RJ. Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans. J Physiol. 2000;523 Pt 1:259-70.
61. Moossavi A, Mohsen S. Noninvasive neuromodulation of tinnitus with transcranial current stimulation techniques with insight into neurobiology and neuroimaging. Aud Vest Res. 2016;25(2):89-97.
62. De Ridder D, Vanneste S. EEG driven tDCS versus bifrontal tDCS for tinnitus. Front Psychiatry. 2012;3:84. doi: 10.3389/fpsyt.2012.00084
63. Müller N, Lorenz I, Langguth B, Weisz N. rTMS induced tinnitus relief is related to an increase in auditory cortical alpha activity. PLoS One. 2013;8(2):e55557. doi: 10.1371/journal.pone.0055557
64. Faber M, Vanneste S, Fregni F, De Ridder D. Top down prefrontal affective modulation of tinnitus with multiple sessions of tDCS of dorsolateral prefrontal cortex. Brain Stimul. 2012;5(4):492-8. doi: 10.1016/j.brs.2011.09.003
65. Mohsen S, Pourbakht A, Farhadi M, Mahmoudian S. The efficacy and safety of multiple sessions of multisite transcranial Random Noise Stimulation (tRNS) in treating chronic tinnitus. Brazilian Journal of Otorhinolaryngology. 2018;(In Press)/ Available from:
66. To WT, Ost J, Hart J Jr, De Ridder D, Vanneste S. The added value of auditory cortex transcranial random noise stimulation (tRNS) after bifrontal transcranial direct current stimulation (tDCS) for tinnitus. J Neural Transm (Vienna). 2017;124(1):79-88. doi: 10.1007/s00702-016-1634-2
67. Mohsen S, Mahmoudian S, Talebian S, Pourbakht A. Prefrontal and auditory tRNS in sequence for treating chronic tinnitus: a modified multisite protocol. Brain Stimul. 2018. pii: S1935-861X(18)30140-2. doi: 10.1016/j.brs.2018.04.018
68. Spiegel DP, Linford T, Thompson B, Petoe MA, Kobayashi K, Stinear CM, et al. Multisensory attention training for treatment of tinnitus. Sci Rep. 2015;5:10802. doi: 10.1038/srep10802
How to Cite
Mohsen S, Pourbakht A. An overview of the tinnitus network activity and its clinical implications. AVR. 27(4).
Review Article(s)