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Towards a Mechanistic-Driven Precision Medicine Approach for Tinnitus

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Abstract

In this position review, we propose to establish a path for replacing the empirical classification of tinnitus with a taxonomy from precision medicine. The goal of a classification system is to understand the inherent heterogeneity of individuals experiencing and suffering from tinnitus and to identify what differentiates potential subgroups. Identification of different patient subgroups with distinct audiological, psychophysical, and neurophysiological characteristics will facilitate the management of patients with tinnitus as well as the design and execution of drug development and clinical trials, which, for the most part, have not yielded conclusive results. An alternative outcome of a precision medicine approach in tinnitus would be that additional mechanistic phenotyping might not lead to the identification of distinct drivers in each individual, but instead, it might reveal that each individual may display a quantitative blend of causal factors. Therefore, a precision medicine approach towards identifying these causal factors might not lead to subtyping these patients but may instead highlight causal pathways that can be manipulated for therapeutic gain. These two outcomes are not mutually exclusive, and no matter what the final outcome is, a mechanistic-driven precision medicine approach is a win-win approach for advancing tinnitus research and treatment. Although there are several controversies and inconsistencies in the tinnitus field, which will not be discussed here, we will give a few examples, as to how the field can move forward by exploring the major neurophysiological tinnitus models, mostly by taking advantage of the common features supported by all of the models. Our position stems from the central concept that, as a field, we can and must do more to bring studies of mechanisms into the realm of neuroscience.

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References

  • Adams PF, Hendershot GE, Marano MA, C. Centers for Disease, S. Prevention/National Center for Health (1999) Current estimates from the National Health Interview Survey, 1996. Vital Health Stat 10:1–203

    Google Scholar 

  • Adjamian P (2014) The application of electro- and magneto-encephalography in tinnitus research - methods and interpretations. Front Neurol 5:228

    Article  PubMed  PubMed Central  Google Scholar 

  • Adjamian P, Sereda M, Zobay O, Hall DA, Palmer AR (2012) Neuromagnetic indicators of tinnitus and tinnitus masking in patients with and without hearing loss. J Assoc Res Otolaryngol 13:715–731

    Article  PubMed  PubMed Central  Google Scholar 

  • Araneda R, de Volder AG, Deggouj N, Philippot P, Heeren A, Lacroix E, Decat M, Rombaux P, Renier L (2015) Altered top-down cognitive control and auditory processing in tinnitus: evidences from auditory and visual spatial stroop. Restor Neurol Neurosci 33:67–80

    PubMed  Google Scholar 

  • Attias J, Pratt H, Reshef I, Bresloff I, Horowitz G, Polyakov A, Shemesh Z (1996) Detailed analysis of auditory brainstem responses in patients with noise-induced tinnitus. Audiology 35:259–270

    Article  CAS  PubMed  Google Scholar 

  • Baguley DM (2003) Hyperacusis. J R Soc Med 96:582–585

    Article  PubMed  PubMed Central  Google Scholar 

  • Baguley DM, McFerran DJ (2010) Hyperacusis and disorders of loudness perceptionHyperacusis and disorders of loudness perception. In: Møller A, Langguth B, De Ridder D, Kleinjung T (eds) Textbook of Tinnitus. Springer, New York, pp 13–23

    Google Scholar 

  • Barnea G, Attias J, Gold S, Shahar A (1990) Tinnitus with normal hearing sensitivity: extended high-frequency audiometry and auditory-nerve brain-stem-evoked responses. Audiology 29(1):36–45

  • Bauer CA (2018) Tinnitus. N Engl J Med 378:1224–1231

    Article  PubMed  Google Scholar 

  • Caspary DM, Llano DA (2017) Auditory thalamic circuits and GABAA receptor function: putative mechanisms in tinnitus pathology. Hear Res 349:197–207

    Article  CAS  PubMed  Google Scholar 

  • Chery-Croze S, Moulin A, Collet L, Morgon A (1994) Is the test of medial efferent system function a relevant investigation in tinnitus? Br J Audiol 28:13–25

    Article  CAS  PubMed  Google Scholar 

  • Choi S, Yu E, Hwang E, Llinas RR (2016) Pathophysiological implication of CaV3.1 T-type Ca2+ channels in trigeminal neuropathic pain. Proc Natl Acad Sci U S A 113:2270–2275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corliss EL, Burnett ED, Stimson HF (1968) "Polyacusis", a hearing anomaly. J Acoust Soc Am 43:1231–1236

    Article  CAS  PubMed  Google Scholar 

  • da Cruz Fernandes L, Momensohn-Santos TM, Carvalho JSM, de Queiroz Carvalho FL (2013) Tinnitus and normal hearing: A study on contralateral acoustic reflex. Am J Audiol 22(2):291–296

    Article  Google Scholar 

  • de Leede-Smith S, Barkus E (2013) A comprehensive review of auditory verbal hallucinations: lifetime prevalence, correlates and mechanisms in healthy and clinical individuals. Front Hum Neurosci 7:367

    PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  • Delb W, Strauss DJ, Low YF, Seidler H, Rheinschmitt A, Wobrock T, D’Amelio R (2008) Alterations in Event Related Potentials (ERP) associated with tinnitus distress and attention. Appl Psychophysiol Biofeedback 33(4):211–221

    Article  PubMed  Google Scholar 

  • Destexhe A, Contreras D, Steriade M (1998) Mechanisms underlying the synchronizing action of corticothalamic feedback through inhibition of thalamic relay cells. J Neurophysiol 79:999–1016

    Article  CAS  PubMed  Google Scholar 

  • Diesch E, Andermann M, Flor H, Rupp A (2010). Interaction among the components of multiple auditorys steady-state responses: enhancement in tinnitus patients, inhibition in controls. Neuroscience 167(2):540–553

  • Dornhoffer J, Danner C, Mennemeier M, Blake D, Garcia-Rill E (2006) Arousal and attention deficits in patients with tinnitus. Int Tinnitus J 12(1):9

    PubMed  Google Scholar 

  • dos Santos Filha VAV, Matas CG (2010) Late Auditory evoked potentials in individuals with tinnitus. Braz J Otorhinolaryngol 76(2):263–270

    Article  PubMed  Google Scholar 

  • Eggermont JJ, Roberts LE (2004) The neuroscience of tinnitus. Trends Neurosci 27:676–682

    Article  CAS  PubMed  Google Scholar 

  • Epp B, Hots J, Verhey JL, Schaette R (2012) Increased intensity discrimination thresholds in tinnitus subjects with a normal audiogram. J Acoust Soc Am 132:EL196–EL201

    Article  CAS  PubMed  Google Scholar 

  • Fabijanska A et al (2012) The relationship between distortion product otoacoustic emissions and extended high-frequency audiometry in tinnitus patients. Part 1: normally hearing patients with unilateral tinnitus. Med Sci Monit 18:CR765–CR770

    Article  PubMed  PubMed Central  Google Scholar 

  • Favero ML, Sanchez TG, Bento RF, Nascimento AF (2006) Contralateral suppression of otoacoustic emission in patients with tinnitus. Braz J Otorhinolaryngol 72:223–226

    Article  PubMed  Google Scholar 

  • Fernandes Lda C, Momensohn-Santos TM, Carvalho JS, Carvalho FL (2013) Tinnitus and normal hearing: a study on contralateral acoustic reflex. Am J Audiol 22:291–296

    Article  PubMed  Google Scholar 

  • Fournier P, Hebert S (2013) Gap detection deficits in humans with tinnitus as assessed with the acoustic startle paradigm: does tinnitus fill in the gap? Hear Res 295:16–23

    Article  PubMed  Google Scholar 

  • Galazyuk A, Hebert S (2015) Gap-Prepulse inhibition of the acoustic startle reflex (GPIAS) for tinnitus assessment: current status and future directions. Front Neurol 6:88

    Article  PubMed  PubMed Central  Google Scholar 

  • Gerken GM, Hesse PS, Wiorkowski JJ (2001) Auditory evoked responses in control subjects and in patients with problem-tinnitus. Hear Res 157(1):52–64

    Article  CAS  PubMed  Google Scholar 

  • Ghuman AS, Bar M, Dobbins IG, Schnyer DM (2008) The effects of priming on frontal-temporal communication. Proc Natl Acad Sci U S A 105:8405–8409

    Article  PubMed  PubMed Central  Google Scholar 

  • Ghuman AS, McDaniel JR, Martin A (2011) A wavelet-based method for measuring the oscillatory dynamics of resting-state functional connectivity in MEG. Neuroimage 56:69–77

    Article  PubMed  PubMed Central  Google Scholar 

  • Ghuman AS, van den Honert RN, Martin A (2013) Interregional neural synchrony has similar dynamics during spontaneous and stimulus-driven states. Sci Rep 3:1481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gilani VM, Ruzbahani M, Mahdi P, Amali A, Khoshk MHN, Sameni J et al (2013) Temporal processing evaluation in tinnitus patients: results on analysis of gap in noise and duration pattern test. Iran J Otorhinolaryngol 25(73):221

    Google Scholar 

  • Goldstein B, Shulman A (1999) Central auditory speech test findings in individuals with subjective idiopathic tinnitus. Int Tinnitus J 5:16–19

    CAS  PubMed  Google Scholar 

  • Gross J, Hoogenboom N, Thut G, Schyns P, Panzeri S, Belin P, Garrod S (2013) Speech rhythms and multiplexed oscillatory sensory coding in the human brain. PLoS Biol 11:e1001752

    Article  PubMed  PubMed Central  Google Scholar 

  • Guest H, Munro KJ, Prendergast G, Howe S, Plack CJ (2017) Tinnitus with a normal audiogram: relation to noise exposure but no evidence for cochlear synaptopathy. Hear Res 344:265–274

    Article  PubMed  PubMed Central  Google Scholar 

  • Haenggeli CA, Pongstaporn T, Doucet JR, Ryugo DK (2005) Projections from the spinal trigeminal nucleus to the cochlear nucleus in the rat. J Comp Neurol 484:191–205

    Article  PubMed  Google Scholar 

  • Hartline HK, Wagner HG, Ratliff F (1956) Inhibition in the eye of limulus. J Gen Physiol 39:651–673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hebert S, Fournier P, Norena A (2013) The auditory sensitivity is increased in tinnitus ears. J Neurosci 33:2356–2364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henry JA (2016) "Measurement" of tinnitus. Otol Neurotol 37:e276–e285

    Article  PubMed  Google Scholar 

  • Henry JA, Meikle MB (2000) Psychoacoustic measures of tinnitus. J Am Acad Audiol 11:138–155

    CAS  PubMed  Google Scholar 

  • Horowitz G, Polyakov A, Shemesh Z (1996) Detailed analysis of auditory brainstem responses in patients with noise-induced tinnitus. Audiology 35(5):259–270

    Article  PubMed  Google Scholar 

  • Jacobson GP, McCaslin DL (2003) A reexamination of the long latency N1 response in patients with tinnitus. J Am Acad Audiol 14(7):393–400

    PubMed  Google Scholar 

  • Jacobson GP, Calder JA, Newman CW, Peterson EL, Wharton JA, Ahmad BK (1996) Electrophysiological indices of selective auditory attention in subjects with and without tinnitus. Hear Res 97(1):66–74

    Article  CAS  PubMed  Google Scholar 

  • Jahnsen H, Llinas R (1984) Ionic basis for the electro-responsiveness and oscillatory properties of Guinea-pig thalamic neurones in vitro. J Physiol 349:227–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jain C, Sahoo JP (2014) The effect of tinnitus on some psychoacoustical abilities in individuals with normal hearing sensitivity. Int Tinnitus J 19:28–35

    Article  PubMed  Google Scholar 

  • Jastreboff PJ, Jastreboff MM (2000) Tinnitus retraining therapy (TRT) as a method for treatment of tinnitus and hyperacusis patients. J Am Acad Audiol 11:162–177

    CAS  PubMed  Google Scholar 

  • Jastreboff PJ, Jastreboff MM (2015) Decreased sound tolerance: hyperacusis, misophonia, dplacusis, and polycusis. In: Celesia CC, Hickok G (eds) The Human Auditory System. Elsevier, Amsterdam, pp 375–387

    Google Scholar 

  • Johns LC, Kompus K, Connell M, Humpston C, Lincoln TM, Longden E, Preti A, Alderson-Day B, Badcock JC, Cella M, Fernyhough C, McCarthy-Jones S, Peters E, Raballo A, Scott J, Siddi S, Sommer IE, Larøi F (2014) Auditory verbal hallucinations in persons with and without a need for care. Schizophr Bull 40(Suppl 4):S255–S264

    Article  PubMed  PubMed Central  Google Scholar 

  • Jones A, May BJ (2018) Effects of acoustic environment on tinnitus behavior in sound-exposed rats. J Assoc Res Otolaryngol 19:133–146

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  • Kato HK, Asinof SK, Isaacson JS (2017) Network-Level Control of Frequency Tuning in Auditory Cortex. Neuron 95:412–423 e414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keitel A, Ince RAA, Gross J, Kayser C (2017) Auditory cortical delta-entrainment interacts with oscillatory power in multiple fronto-parietal networks. Neuroimage 147:32–42

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim DK, Park SN, Park KH, Choi HG, Jeon EJ, Park YS, Yeo SW (2011) Clinical characteristics and audiological significance of spontaneous otoacoustic emissions in tinnitus patients with normal hearing. J Laryngol Otol 125:246–250

    Article  PubMed  Google Scholar 

  • Knipper M, Van Dijk P, Nunes I, Ruttiger L, Zimmermann U (2013) Advances in the neurobiology of hearing disorders: recent developments regarding the basis of tinnitus and hyperacusis. Prog Neurobiol 111:17–33

    Article  PubMed  Google Scholar 

  • Knyazev GG (2012) EEG delta oscillations as a correlate of basic homeostatic and motivational processes. Neurosci Biobehav Rev 36:677–695

    Article  PubMed  Google Scholar 

  • Konadath S, Manjula P (2016) Auditory brainstem response and late latency response in individuals with tinnitus having normal hearing. Intractable Rare Dis Res 5:262–268

    Article  PubMed  PubMed Central  Google Scholar 

  • Kumar S, Sedley W, Barnes GR, Teki S, Friston KJ, Griffiths TD (2014) A brain basis for musical hallucinations. Cortex 52:86–97

    Article  PubMed  PubMed Central  Google Scholar 

  • Lachaux JP, Rodriguez E, Martinerie J, Varela FJ (1999) Measuring phase synchrony in brain signals. Hum Brain Mapp 8:194–208

    Article  CAS  PubMed  Google Scholar 

  • Langguth B et al (2015) Tinnitus and Headache. Biomed Res Int 2015:797416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Langguth B, Hund V, Landgrebe M, Schecklmann M (2017) Tinnitus patients with comorbid headaches: the influence of headache type and laterality on tinnitus characteristics. Front Neurol 8:440

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee CY, Jaw FS, Pan SL, Lin MY, Young YH (2007) Auditory cortical evoked potentials in tinnitus patients with normal audiological presentation. J Formos Med Assoc 106(12):979–985

    Article  PubMed  Google Scholar 

  • Li S, Choi V, Tzounopoulos T (2013) Pathogenic plasticity of Kv7.2/3 channel activity is essential for the induction of tinnitus. Proc Natl Acad Sci U S A 110:9980–9985

    Article  PubMed  PubMed Central  Google Scholar 

  • Li S, Kalappa BI, Tzounopoulos T (2015) Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and resilience to tinnitus. Elife. 4. https://doi.org/10.7554/eLife.07242

  • Liberman MC, Epstein MJ, Cleveland SS, Wang H, Maison SF (2016) Toward a differential diagnosis of hidden hearing loss in humans. PLoS One 11:e0162726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Llinas RR, Steriade M (2006) Bursting of thalamic neurons and states of vigilance. J Neurophysiol 95:3297–3308

    Article  PubMed  Google Scholar 

  • 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 U S A 96:15222–15227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Llinas R, Urbano FJ, Leznik E, Ramirez RR, van Marle HJ (2005) Rhythmic and dysrhythmic thalamocortical dynamics: GABA systems and the edge effect. Trends Neurosci 28:325–333

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Escamez JA et al (2014) Accompanying symptoms overlap during attacks in Meniere's disease and vestibular migraine. Front Neurol 5:265

    Article  PubMed  PubMed Central  Google Scholar 

  • McCormick DA, Bal T (1997) Sleep and arousal: thalamocortical mechanisms. Annu Rev Neurosci 20:185–215

    Article  CAS  PubMed  Google Scholar 

  • Mehdizade Gilani V, Ruzbahani M, Mahdi P, Amali A, Nilforush Khoshk MH, Sameni J, Karimi Yazdi A, Emami H (2013) Temporal processing evaluation in tinnitus patients: results on analysis of gap in noise and duration pattern test. Iran J Otorhinolaryngol 25:221–226

    PubMed  PubMed Central  Google Scholar 

  • Meikle M, Taylor-Walsh E (1984) Characteristics of tinnitus and related observations in over 1800 tinnitus clinic patients. J Laryngol Otol Suppl 9:17–21

    Article  CAS  PubMed  Google Scholar 

  • Moazami-Goudarzi M, Sarnthein J, Michels L, Moukhtieva R, Jeanmonod D (2008) Enhanced frontal low and high frequency power and synchronization in the resting EEG of parkinsonian patients. Neuroimage 41:985–997

    Article  PubMed  Google Scholar 

  • Møller A (2010) Misophonia, phonophobia and “exploding head” syndrome. In: Møller A, Langguth B, De Ridder D, Kleinjung T (eds) Textbook oo Tinnitus. Springer, New York, pp 25–27

    Google Scholar 

  • Moon IJ, Won JH, Kang HW, Kim DH, An YH, Shim HJ (2015) Influence of tinnitus on auditory spectral and temporal resolution and speech perception in tinnitus patients. J Neurosci 35:14260–14269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moore BC, Vinay, Sandhya (2010) The relationship between tinnitus pitch and the edge frequency of the audiogram in individuals with hearing impairment and tonal tinnitus. Hear Res 261:51–56

    Article  PubMed  Google Scholar 

  • Moore AK, Weible AP, Balmer TS, Trussell LO, Wehr M (2018) Rapid Rebalancing of Excitation and Inhibition by Cortical Circuitry. Neuron 97:1341–1355 e1346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagel G, Szellas T, Huhn W, Kateriya S, Adeishvili N, Berthold P, Ollig D, Hegemann P, Bamberg E (2003) Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci U S A 100:13940–13945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Newman CW, Wharton JA, Shivapuja BG, Jacobson GP (1994) Relationships among psychoacoustic judgments, speech understanding ability and self-perceived handicap in tinnitus subjects. Audiology 33:47–60

    Article  CAS  PubMed  Google Scholar 

  • Newman CW, Jacobson GP, Spitzer JB (1996) Development of the tinnitus handicap inventory. Arch Otolaryngol Head Neck Surg 122:143–148

    Article  CAS  PubMed  Google Scholar 

  • Norena AJ (2011) An integrative model of tinnitus based on a central gain controlling neural sensitivity. Neurosci Biobehav Rev 35:1089–1109

    Article  PubMed  Google Scholar 

  • Norena A, Cransac H, Chery-Croze S (1999) Towards an objectification by classification of tinnitus. Clin Neurophysiol 110(4):666–675

    Article  CAS  PubMed  Google Scholar 

  • Omidvar S et al (2016) The relationship between ultra-high frequency thresholds and transient evoked otoacoustic emissions in adults with tinnitus. Med J Islam Repub Iran 30:449

    PubMed  PubMed Central  Google Scholar 

  • Paglialonga A, Del Bo L, Ravazzani P, Tognola G (2010) Quantitative analysis of cochlear active mechanisms in tinnitus subjects with normal hearing sensitivity: multiparametric recording of evoked otoacoustic emissions and contralateral suppression. Auris Nasus Larynx 37:291–298

    Article  PubMed  Google Scholar 

  • Pan T, Tyler RS, Ji H, Coelho C, Gehringer AK, Gogel SA (2009) The relationship between tinnitus pitch and the audiogram. Int J Audiol 48:277–294

    Article  PubMed  Google Scholar 

  • Paul BT, Bruce IC, Roberts LE (2017) Evidence that hidden hearing loss underlies amplitude modulation encoding deficits in individuals with and without tinnitus. Hear Res 344:170–182

    Article  PubMed  Google Scholar 

  • Pierzycki RH, McNamara AJ, Hoare DJ, Hall DA (2016) Whole scalp resting state EEG of oscillatory brain activity shows no parametric relationship with psychoacoustic and psychosocial assessment of tinnitus: a repeated measures study. Hear Res 331:101–108

    Article  PubMed  Google Scholar 

  • Pinheiro ES et al (2016) Electroencephalographic patterns in chronic pain: a systematic review of the literature. PLoS One 11:e0149085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinto PC et al (2014) Tinnitus and its association with psychiatric disorders: systematic review. J Laryngol Otol 128:660–664

    Article  CAS  PubMed  Google Scholar 

  • Rauschecker JP, Leaver AM, Muhlau M (2010) Tuning out the noise: limbic-auditory interactions in tinnitus. Neuron 66:819–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rauschecker JP, May ES, Maudoux A, Ploner M (2015) Frontostriatal gating of tinnitus and chronic pain. Trends Cogn Sci 19:567–578

    Article  PubMed  PubMed Central  Google Scholar 

  • Reed GF (1960) An audiometric study of two hundred cases of subjective tinnitus. AMA Arch Otolaryngol 71:84–94

    Article  CAS  PubMed  Google Scholar 

  • Riga M, Papadas T, Werner JA, Dalchow CV (2007) A clinical study of the efferent auditory system in patients with normal hearing who have acute tinnitus. Otol Neurotol 28:185–190

    Article  PubMed  Google Scholar 

  • Ryu IS, Ahn JH, Lim HW, Joo KY, Chung JW (2012) Evaluation of masking effects on speech perception in patients with unilateral chronic tinnitus using the hearing in noise test. Otol Neurotol 33:1472–1476

    Article  PubMed  Google Scholar 

  • Sarnthein J, Jeanmonod D (2007) High thalamocortical theta coherence in patients with Parkinson's disease. J Neurosci 27:124–131

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Schaette R, McAlpine D (2011) Tinnitus with a normal audiogram: physiological evidence for hidden hearing loss and computational model. J Neurosci 31:13452–13457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schecklmann M, Vielsmeier V, Steffens T, Landgrebe M, Langguth B, Kleinjung T (2012) Relationship between audiometric slope and tinnitus pitch in tinnitus patients: insights into the mechanisms of tinnitus generation. PLoS One 7:e34878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schecklmann M, Landgrebe M, Langguth B, T. R. I. D. S. Group (2014) Phenotypic characteristics of hyperacusis in tinnitus. PLoS One 9:e86944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schlee W, Weisz N, Bertrand O, Hartmann T, Elbert T (2008). Using auditory steady state responses to outline the functional connectivity in tinnitus brain. PLoS One 3(11):e3720

  • Schurger A, Sarigiannidis I, Naccache L, Sitt JD, Dehaene S (2015) Cortical activity is more stable when sensory stimuli are consciously perceived. Proc Natl Acad Sci U S A 112:E2083–E2092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sedley W, Friston KJ, Gander PE, Kumar S, Griffiths TD (2016) An integrative tinnitus model based on sensory precision. Trends Neurosci 39:799–812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seidman MD, Jacobson GP (1996) Update on tinnitus. Otolaryngol Clin N Am 29:455–465

    CAS  Google Scholar 

  • Sereda M, Hall DA, Bosnyak DJ, Edmondson-Jones M, Roberts LE, Adjamian P, Palmer AR (2011) Re-examining the relationship between audiometric profile and tinnitus pitch. Int J Audiol 50:303–312

    Article  PubMed  PubMed Central  Google Scholar 

  • Seydell-Greenwald A, Leaver AM, Turesky TK, Morgan S, Kim HJ, Rauschecker JP (2012) Functional MRI evidence for a role of ventral prefrontal cortex in tinnitus. Brain Res 1485:22–39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shargorodsky J, Curhan GC, Farwell WR (2010) Prevalence and characteristics of tinnitus among US adults. Am J Med 123:711–718

    Article  PubMed  Google Scholar 

  • Shekhawat GS, Searchfield GD, Stinear CM (2014) The relationship between tinnitus pitch and hearing sensitivity. Eur Arch Otorhinolaryngol 271:41–48

    Article  PubMed  Google Scholar 

  • Sheldrake J, Diehl PU, Schaette R (2015) Audiometric characteristics of hyperacusis patients. Front Neurol 6:105

    Article  PubMed  PubMed Central  Google Scholar 

  • Shim HJ, Kim SK, Park CH, Lee SH, Yoon SW, Ki AR et al (2009) Hearing abilities at ultra-high frequency in patients with tinnitus. Clin Exp Otorhinolaryngol 2(4):169

    Article  PubMed  PubMed Central  Google Scholar 

  • Shiomi Y, Tsuji J, Naito Y, Fujiki N, Yamamoto N (1997) Characteristics of DPOAE audiogram in tinnitus patients. Hear Res 108:83–88

    Article  CAS  PubMed  Google Scholar 

  • Shore SE, Roberts LE, Langguth B (2016) Maladaptive plasticity in tinnitus - triggers, mechanisms and treatment. Nat Rev Neurol 12:150–160

    Article  PubMed  PubMed Central  Google Scholar 

  • Sillito AM, Jones HE (2002) Corticothalamic interactions in the transfer of visual information. Philos Trans R Soc Lond Ser B Biol Sci 357:1739–1752

    Article  Google Scholar 

  • Silva LR, Amitai Y, Connors BW (1991) Intrinsic oscillations of neocortex generated by layer 5 pyramidal neurons. Science 251:432–435

    Article  CAS  PubMed  Google Scholar 

  • Singh S, Munjal SK, Panda NK (2011) Comparison of auditory electrophysiological responses in normal-hearing patients with and without tinnitus. J Laryngol Otol 125:668–672

    Article  CAS  PubMed  Google Scholar 

  • Soleimani R, Jalali MM, Hasandokht T (2016) Therapeutic impact of repetitive transcranial magnetic stimulation (rTMS) on tinnitus: a systematic review and meta-analysis. Eur Arch Otorhinolaryngol 273:1663–1675

    Article  PubMed  Google Scholar 

  • Steriade M (1998) Corticothalamic networks, oscillations, and plasticity. Adv Neurol 77:105–134

    CAS  PubMed  Google Scholar 

  • Steriade M, Contreras D (1995) Relations between cortical and thalamic cellular events during transition from sleep patterns to paroxysmal activity. J Neurosci 15:623–642

    Article  CAS  PubMed  Google Scholar 

  • Steriade M, McCormick DA, Sejnowski TJ (1993) Thalamocortical oscillations in the sleeping and aroused brain. Science 262:679–685

    Article  CAS  PubMed  Google Scholar 

  • Sztuka A, Pospiech L, Gawron W, Dudek K (2010) DPOAE in estimation of the function of the cochlea in tinnitus patients with normal hearing. Auris Nasus Larynx 37:55–60

    Article  PubMed  Google Scholar 

  • Tunkel DE, Bauer CA, Sun GH, Rosenfeld RM, Chandrasekhar SS, Cunningham ER Jr, Archer SM, Blakley BW, Carter JM, Granieri EC, Henry JA, Hollingsworth D, Khan FA, Mitchell S, Monfared A, Newman CW, Omole FS, Phillips CD, Robinson SK, Taw MB, Tyler RS, Waguespack R, Whamond EJ (2014) Clinical practice guideline: tinnitus. Otolaryngol Head Neck Surg 151:S1–S40

    Article  PubMed  Google Scholar 

  • Tyler RS, Pienkowski M, Roncancio ER, Jun HJ, Brozoski T, Dauman N, Coelho CB, Andersson G, Keiner AJ, Cacace AT, Martin N, Moore BCJ (2014) A review of hyperacusis and future directions: part I. Definitions and manifestations. Am J Audiol 23:402–419

    Article  PubMed  Google Scholar 

  • Vanneste S, De Ridder D (2016) Deafferentation-based pathophysiological differences in phantom sound: tinnitus with and without hearing loss. Neuroimage 129:80–94

    Article  PubMed  Google Scholar 

  • Vernon JA, Meikle MB (2003) Tinnitus: clinical measurement. Otolaryngol Clin N Am 36:293–305, vi

    Article  Google Scholar 

  • von Krosigk M, Bal T, McCormick DA (1993) Cellular mechanisms of a synchronized oscillation in the thalamus. Science 261:361–364

    Article  Google Scholar 

  • von Krosigk M, Monckton JE, Reiner PB, McCormick DA (1999) Dynamic properties of corticothalamic excitatory postsynaptic potentials and thalamic reticular inhibitory postsynaptic potentials in thalamocortical neurons of the Guinea-pig dorsal lateral geniculate nucleus. Neuroscience 91:7–20

    Article  Google Scholar 

  • Warren RA, Agmon A, Jones EG (1994) Oscillatory synaptic interactions between ventroposterior and reticular neurons in mouse thalamus in vitro. J Neurophysiol 72:1993–2003

    Article  CAS  PubMed  Google Scholar 

  • Weinbruch C, Paul I, Weisz N, Elbert T, Roberts LE (2006). Frequency organization of the 40-Hz auditory steady-state response in normal hearing and in tinnitus. Neuroimage 33(1):180–194

  • Weisz N, Voss S, Berg P, Elbert T (2004) Abnormal auditory mismatch response in tinnitus sufferers with high-frequency hearing loss is associated with subjective distress level. BMC Neurosci 5:8

    Article  PubMed  PubMed Central  Google Scholar 

  • Weisz N, Muller S, Schlee W, Dohrmann K, Hartmann T, Elbert T (2007) The neural code of auditory phantom perception. J Neurosci 27:1479–1484

    Article  CAS  PubMed  Google Scholar 

  • Welling DB, Jackler RK (2018) Reflections on the last 25 years of the American Otological Society and thoughts on its future. Otol Neurotol 39:S81–S94

    Article  PubMed  Google Scholar 

  • Wojtczak M, Beim JA, Oxenham AJ (2017) Weak middle-ear-muscle reflex in humans with noise-induced tinnitus and Normal hearing May reflect Cochlear Synaptopathy. eNeuro 4:ENEURO.0363–ENEU17.2017

    Article  Google Scholar 

  • Yamawaki N, Shepherd GM (2015) Synaptic circuit organization of motor corticothalamic neurons. J Neurosci 35:2293–2307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang S, Weiner BD, Zhang LS, Cho SJ, Bao S (2011) Homeostatic plasticity drives tinnitus perception in an animal model. Proc Natl Acad Sci U S A 108:14974–14979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu KK, An YH, Won JH, Shim HJ, Yoon SW (2014) Influence of Tinnitus on Auditory Spectral, Temporal Resolution, and Speech Perception Ability in Tinnitus Patients. Otolaryngol Head Neck Surg 151(1_suppl):P210–P210

    Article  Google Scholar 

  • Zhou J, Shore S (2004) Projections from the trigeminal nuclear complex to the cochlear nuclei: a retrograde and anterograde tracing study in the Guinea pig. J Neurosci Res 78:901–907

    Article  CAS  PubMed  Google Scholar 

  • Zhou J, Shore S (2006) Convergence of spinal trigeminal and cochlear nucleus projections in the inferior colliculus of the Guinea pig. J Comp Neurol 495:100–112

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank Drs. Dean Salisbury, Avniel Ghuman, Chris Brown, Bharath Chandrasekaran, Maria Rubio, Barbara Shinn-Cunningham and Karl Kandler for their helpful discussions.

Funding

This work was supported by US Department of Defense grant W81XWH-14-1-0117 and NIH grant R01-DC007905 (both grants to T.T.).

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Correspondence to Thanos Tzounopoulos.

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Tzounopoulos, T., Balaban, C., Zitelli, L. et al. Towards a Mechanistic-Driven Precision Medicine Approach for Tinnitus. JARO 20, 115–131 (2019). https://doi.org/10.1007/s10162-018-00709-9

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  • DOI: https://doi.org/10.1007/s10162-018-00709-9

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