J Am Acad Audiol 2000; 11(03): 125-137
DOI: 10.1055/s-0042-1748039
Original Article

Neurophysiologic Mechanisms of Tinnitus

James A. Kaltenbach
Department of Otolaryngology—Head and Neck Surgery, Wayne State University, Detroit, Michigan
› Author Affiliations

Abstract

Research over the past decade has provided new insights into the neural mechanisms likely to produce the false percepts of sound associated with tinnitus. These insights have emerged mainly as a result of electrophysiologic studies, examining changes in brain activity, and behavioral studies, examining changes in perception, in animals that have been treated with well-known tinnitus inducers such as salicylates, quinine, and intense sound. The available evidence, based on electrophysiologic studies, suggests that tinnitus is associated with disturbances in spontaneous neural activity in the auditory system. These abnormalities include increases in spontaneous activity (hyperactivity), changes in the timing of neural discharges (i.e., the temporal firing properties of neurons), and an increase in bursting activity of neurons. Parallel studies using behavioral testing methods have demonstrated that agents, which produce these neural changes, also cause tinnitus in animals. This article reviews the literature concerned with both behavioral evidence for tinnitus in animal models and the associated changes that occur at peripheral and central levels of the auditory system.

Abbreviations: Al = primary auditory cortex, All = secondary auditory cortex, AFF = anterior auditory field, CF = characteristic frequency, C02 = carbon dioxide, DCN = dorsal cochlear nucleus, EEG = electroencephalogram, FMRI = functional magnetic resonance imaging, IC = inferior colliculus, OAEs = otoacoustic emissions, PET = positron emission tomography, SA = spontaneous activity, SOAEs = spontaneous otoacoustic emissions



Publication History

Article published online:
07 April 2022

© 2000. American Academy of Audiology. This article is published by Thieme.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • REFERENCES

  • Alder VA. (1978). Neural Correlates of Auditory Temporary Threshold Shift. Doctoral dissertation, University of Western Australia,
  • Axelsson A, Barrenas ML. (1992). Tinnitus in noise-induced hearing loss. In: Dancer AL, Henderson D, Salvi RJ, Hamernik RP, eds. Noise-Induced Hearing Loss. Boston: Mosby Year Book, 269–276.
  • Axelsson A, Sandh A. (1985). Tinnitus in noise-induced hearing loss. BrJAudiol 19:271–276.
  • Bauer CA, Brozowski TJ, Caspary DM, Rojas R, Boley J, Wyder M, Hindes A. (1998). The effects of salicylate on conditioned suppression behavior and receptor pharmacology in the inferior colliculus of the Long-Evans rat. ARO Abs 21:203.
  • Bauer CA, Herr LA, Brozowski TJ. (1999). Behavioral evidence of chronic tinnitus in rats after unilateral noise trauma. ARO Abs 22:154.
  • Cacace AT, Cousins JP, Moonen CTW, van Gelderen P, Miller D, Parnes SM, Lovely TJ. (1996). In-vivo localization of phantom auditory perceptions during functional magnetic resonance imaging of the human brain. In: Reich G, ed. Proceedings of the 5th International Tinnitus Seminar. Portland, OR: American Tinnitus Association, 397–401.
  • Cahani M, Paul G, Shahar A. (1983). Tinnitus pitch and acoustic trauma. Audiology 22:357–363.
  • Cazals Y, Horner KC, Huang ZW. (1998). Alterations in average spectrum of cochleoneural activity by long-term salicylate treatment in the guinea pig: a plausible index of tinnitus. J Neurophysiol 80:2113–2120.
  • Cazals Y, Huang ZW (1996). Average spectrum of cochlear activity: a possible synchronized firing, its olivocochlear feedback and alterations under anesthesia. Hear Res 101:81–92.
  • Ceranic JB, Prasher DK, Luxon LM. (1995). Tinnitus and otoacoustic emissions. Clin Otolaryngol 20:192–200.
  • Chen GD, Jastreboff PJ. (1995). Salicylate-induced abnormal activity in the inferior colliculus of rats. Hear Res 82:158–178.
  • Coles RRA. (1995). Classification of causes, mechanisms of patient disturbance, and associated counceling. In: Vernon JA, Moller AR, eds. Mechanisms of Tinnitus. Boston: Allyn and Bacon, 11–20.
  • Dandy WE. (1941). Surgical treatment of Meniere's disease. Surg Gyn Obstet 72:421–425.
  • Davis Η. (1983). An active process in cochlear mechanics. Hear Res 9:79–90.
  • Day RO, Graham GG, Bieri D, Brown M, Cairns D, Harris G, Hounsell J, Platt-Hepworth S, Reeve R, Sambrook PM, Smith J. (1989). Concentration-response relationships for salicylate-induced ototoxicity in normal volunteers. Br J Clin Pharmacol 28:695–702.
  • Denk DM, Heinzl H, Frank P, Ehrenberger K. (1997). Caroverine in tinnitus treatment. A placebo-controlled blind study. Acta Otolaryngol 117:825–830.
  • Dolan DF, Nuttall AL, Avinash G. (1990). Asynchronous neural activity recorded from the round window. J Acoust Soc Am 87:2621–2627.
  • Drescher MJ, Drescher DG. (1992). Glutamate, of the endogenous primary a-amino acids, is specifically released from hair cells by elevated extracellular potassium. J Neurochem 59:93–98.
  • Eggermont JJ, Kenmochi M. (1998). Salicylate and quinine selectively increase spontaneous firing rates in secondary auditory cortex. Hear Res 117:149–160.
  • Eggermont JJ, Sininger Y. (1995). Correlated neural activity and tinnitus. In: Vernon JA, Moller AR, eds. Mechanisms of Tinnitus. Boston: Allyn and Bacon, 21–34.
  • Ehrenberger K, Brix R. (1983). Glutamic acid and glutamic acid diethylester in tinnitus treatment. Acta Otolaryngol 95:599–605.
  • Ehrenberger K, Felix D. (1991). Glutamate receptors in afferent cochlear neurotransmission in guinea pigs. Hear Res 52:73–80.
  • Ehrenberger K, Felix D. (1992). Caroverine depresses the activity of cochlear glutamate receptors in guinea pigs: in vivo model for drug-induced neuroprotection. Neuropharmacology 31:1259–1263.
  • Ehrenberger K, Felix D. (1995). Receptor pharmacological models for inner ear therapies with emphasis on glutamate receptors: a survey. Acta Otolaryngol 115: 236–240.
  • Evans EF. (1978) Place and time coding of frequency in the peripheral auditory system: some physiological pros and cons. Audiology 17:369–420.
  • Evans EF, Borerwe TA. (1982). Ototoxic effects of salicylates on the responses of single cochlear nerve fibres and on cochlear potentials. Br J Audiol 16:101–108.
  • Evans EF, Wilson JP, Borerwe TA. (1981). Animal models of tinnitus. In: Evered D, Lawrenson G, eds. Tinnitus. London: Pitman, 108–129.
  • Gejrot T. (1963). Intravenous Xylocaine in the treatment of attacks on Meniere's disease. Acta Otolaryngol Suppl 188:190–195.
  • Gerken GM, Saunders SS, Paul RE. (1984). Hypersensitivity to electrical stimulation of auditory nuclei follows hearing loss in cats. Hear Res 13:249–259.
  • Harrison RV, Nagasawa A, Smith DV, Stanton S, Mount RJ. (1991). Reorganization of auditory cortex after neonatal high frequency hearing loss. Hear Res 54:11–19.
  • Harrison RV, Prijs VF. (1984). Single cochlear fiber responses in guinea pig with long term endolymphatic hydrops. Hear Res 14:79–84.
  • Heffner HE, Kaltenbach JA. (1999). Behavioral evidence for tinnitus in hamsters following exposure to loud sound. ARO Abs 22:183.
  • House JW, Brackman DE. (1981). Tinnitus: surgical treatment. In: Evered D, Lawrenson G, eds. Tinnitus. London: Pitman, 204–216.
  • Irvine DR, Rajan R. (1997). Injury-induced reorganization of frequency maps in adult auditory cortex: the role of unmasking of normally-inhibited inputs. Acta Otolaryngol Suppl 532:39–45.
  • 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 97:66–74.
  • Jannetta PJ. (1987). Microvascular decompression of cochlear nerve as a treatment for tinnitus. In: Feldmann Η, ed. Proceedings of the 3rd International Tinnitus Seminar. Karlsruhe, West Germany: Harsch Verlag, 348–352.
  • Jastreboff PJ, Brennan JE (1992). The psychophysical characteristics of tinnitus in rats. In: Aran J, Dauman R, eds. Proceedings of the 4th International Tinnitus Seminar. Amsterdam: Kugler, 305–308.
  • Jastreboff PJ, Brennan JE (1994). Evaluating the loudness of phantom auditory perception (tinnitus) in rats. Audiology 33:202–217.
  • Jastreboff PJ, Brennan JE Coleman JK, Sasaki CT. (1988a). Phantom auditory sensation in rats: an animal model for tinnitus. Behau Neurosci 102:811–822.
  • Jastreboff PJ, Brennan JE Sasaki CT. (1988b). An animal model for tinnitus. Laryngoscope 98:280–286.
  • Jastreboff PJ, Brennan JE Sasaki CT. (1991). Quinine-induced tinnitus in rats. Arch Otolaryngol 117:1162–1166.
  • Jastreboff PJ, Jastreboff MM, Song H, Hu S. (1997). An animal model of tinnitus related to sound-induced hearing loss. ARO Abs 20:32.
  • Jastreboff PJ, Zhou S, Jastreboff MM, Kwapisz U, Gryczynska U. (1997). Attenuation of salicylate-induced tinnitus by Ginkgo biloba extract in rats. Audiol Neuro-otol 2:197–212.
  • Kaltenbach JA, Godfrey DA, McCaslin DL, Squire AB. (1996). Changes in spontaneous activity and chemistry of the cochlear nucleus following intense sound exposure. In: Reich G, ed. Proceedings of the 5th International Tinnitus Seminar. Portland, OR: American Tinnitus Association, 34–45.
  • Kaltenbach JA, Godfrey DA, Neumann JB, McCaslin DL, Afman CE, Zhang JS. (1998). Changes in spontaneous neural activity in the dorsal cochlear nucleus following exposure to intense sound: relation to threshold shift. Hear Res 124:78–84.
  • Kaltenbach JA, Heffner HE. (1999). Spontaneous activity in the dorsal cochlear nucleus of hamsters tested behaviorally for tinnitus. ARO Abs 22:47.
  • Kaltenbach JA, McCaslin DL. (1996). Increases in spontaneous activity in the dorsal cochlear nucleus following exposure to high intensity sound: a possible neural correlate of tinnitus. Audiol Neurosci 3:57–78.
  • Karlsson KK, Flock A. (1990). The effect of quinine on
  • psychophysical tuning curves, stapedius reflexes and evoked otoacoustic emissions in healthy volunteers. Scand Audiol 20:83–90.
  • Kauer JS, Nemitz JW, Sasaki CT. (1982). Tinnitus aurium: fact or fancy. Laryngoscope 92:1401–1407.
  • Kenmochi M, Eggermont JJ. (1997). Salicylate and quinine affect the central nervous system. Hear Res 113:110–116.
  • Kumagai M. (1992). Effect of intravenous injection of aspirin on the cochlea. Hokkaido J Med Sci 67:216–233.
  • Lenarz T, Schreiner C, Snyder RL, Ernst A. (1995). Neural mechanisms of tinnitus. In: Vernon JA, Moller AR, eds. Mechanisms of Tinnitus. Boston: Allyn and Bacon, 101–113.
  • Lenarz TH, Schreiner CE. (1990). Pharmacological modifications of abnormal ensemble spontaneous activity of cat auditory nerve. ARO Abs 13:198.
  • Levine RA. (1999). Somatic (craniocervical) tinnitus: a pivotal role for dorsal cochlear nucleus? ARO Abs 22:6.
  • Liberman MC, Dodds LW. (1984). Single neuron labeling and chronic cochlear pathology. II. Stereocilia damage and alterations of spontaneous discharge rates. Hear Res 16:43–53.
  • Liberman MC, Kiang NY-S. (1978). Acoustic trauma in cats. Acta Otolaryngol Suppl 358:1–63.
  • Lin X, Chen S, Tee D. (1998). Effects of quinine on the excitability and voltage-dependent currents of isolated spiral ganglion neurons in culture. J Neurophysiol 79:2503–2512.
  • Lockwood AH, Salvi RJ, Coad ML, Towsley ML, Wack DS, Murphy BW. (1998). The functional neuroanatomy of tinnitus: evidence for limbic system links and neural plasticity. Neurology 50:114–120.
  • Lonsbury-Martin BL, Martin GK. (1981). Effects of moderately intense sounds on auditory sensitivity in Rhesus monkeys: behavioral and neural observations. J Neurophysiol 46:563–586.
  • Man A, Naggan L. (1981). Characteristics of tinnitus in acoustic trauma. Audiology 20:70–78.
  • Manabe Y, Saito T, Saito H. (1997). Effects of lidocaine on salicylate-induced discharges of neurons in the inferior colliculus of the guinea pig. Hear Res 103:192–198.
  • Martin W (1995). Spectral analysis of brain activity in the study of tinnitus. In: Vernon JA, Moller AR, eds. Mechanisms of Tinnitus. Boston: Allyn and Bacon, 163–180.
  • Martin WH, Schwegler JW, Scheibelhoffer J, Ronis ML. (1993). Salicylate-induced changes in cat auditory nerve activity. Laryngoscope 103:600–604.
  • McCabe PA, Dey FL. (1965). The effect of aspirin upon auditory sensitivity. Ann Otol Rhinol Laryngol 74: 312–324.
  • McFadden D. (1982). Tinnitus. Facts, Theories, and Treatments. Washington, DC: National Academy Press.
  • McFadden D, Plattsmier HS, Pasanen EG. (1984). Aspirin-induced hearing loss as a model of sensorineural hearing loss. Hear Res 16:251–260.
  • Meikle MB. (1995). The interaction of central and peripheral mechanisms in tinnitus. In: Vernon JA, Moller AR, eds. Mechanisms of Tinnitus. Boston: Allyn and Bacon, 181–206.
  • Meikle MB, Creedon TA, Charnell MG, Lilly JE. (1996). Tinnitus information for the 21st century: statistica via the internet. In: Reich G, ed. Proceedings of the 5th International Tinnitus Seminar. Portland, OR: American Tinnitus Association, 275–282.
  • Meikle M, Taylor-Walsh E. (1984). Characteristics of tinnitus and related observations in over 1800 tinnitus patients. J Laryngol Otol Suppl 9:17–21.
  • Melding PS, Goodey RJ, Thorne PR. (1978). The use of intravenous lignocaine in the diagnosis and treatment of tinnitus. J Laryngol Otol 92:115–121.
  • Moller AR. (1984). Pathophysiology of tinnitus. Are« Otol Rhinol Laryngol 93:39–44.
  • Moller AR. (1995). Pathophysiology of tinnitus. In: Vernon JA, Moller AR, eds. Mechanisms of Tinnitus. Boston: Allyn and Bacon, 207–218.
  • Moller MB, Moller AR, Jannetta PJ, Jho HD. (1993). Vascular decompression surgery for severe tinnitus: selection criteria and results. Laryngoscope 103:421–427.
  • Mongan E, Kelly P, Nies K, Porter WW, Paulus HE. (1973). Tinnitus as an indication of therapeutic serum salicylate levels. JAMA 226:142–145.
  • Muhlnickel W, Elbert T, Taub E, Flor Η. (1998). Reorganization of auditory cortex. Proc Natl Acad Sci USA 95:10340–10343.
  • Mulheran M. (1990). The Effects of Systemic Blood Pressure, Salicylate and Quinine on the Activity of the Guinea Pig Auditory Nerve. Doctoral dissertation, Staffordshire, University of Keele, United Kingdom.
  • Mulheran M, Evans EF. (1999). A comparison of two experimental tinnitogenic agents: the effect of salicylate an dquinine on activity of cochlear nerve fibers in the guinea pig. In: Hazell J, ed. Proceedings of the 6th International Tinnitus Seminar. Cambridge, UK: The Tinnitus and Hyperacusis Centre, London, 1989–192.
  • Newman CW, Wharton JA, Jacobson GP. (1997). Self-focused and somatic attention in patients with tinnitus. J Am Acad Audiol 8:143–149.
  • Norton SJ, Schmidt AR, Stover LJ. (1990). Tinnitus and otoacoustic emissions: is there a link? Ear Hear 11: 159–166.
  • Ochi K, Eggermont JJ. (1996). Effects of salicylate on neural activity in cat primary auditory cortex. Hear Res 95:63–76.
  • Ochi K, Eggermont JJ. (1997). Effects of quinine on neural activity in cat primary auditory cortex. Hear Res 105: 105–118.
  • Oestreicher E, Arnold W, Ehrenberger K, Felix D. (1998). Memantine suppresses the glutamate neurotransmission of mammalian inner hair cells. J Otol Rhinol Laryngol 60:18–21.
  • Penner Μ J. (1990). An estimate of the prevalence of tinnitus caused by spontaneous otoacoustic emissions. Arch Otolaryngol Head Neck Surg 116:418–423.
  • Penner MJ, Bilger RC. (1995). Psychophysical observations and the origin of tinnitus. In: Vernon JA, Moller AR, eds. Mechanisms of Tinnitus. Boston: Allyn and Bacon, 219–230.
  • Plinkert PK, Gitter AH, Zenner HP. (1990). Tinnitus associated spontaneous otoacoustic emissions. Active outer hair cell movements as common origin? Acta Otolaryngol 110:342–347.
  • Powers NL, Salvi RJ, Wang J, Spongr V, Qiu CX. (1995) Elevation of auditory thresholds by spontaneous cochlear oscillations. Nature 375:585–587.
  • Puel J-L, Bobbin RP, Fallon M. (1990). Salicylate, mefe-namate, meclogenamate, and quinine on cochlear potentials. Otolaryngol Head Neck Surg 102:66–73.
  • Rajan R, Irvine DR, Calford BM, Wise LZ. (1992). Effect of frequency specific losses in cochlear neural sensitivity on the processing and representation of frequency in primary auditory cortex. In: Dancer AL, Henderson D, Salvi RJ, Hamernik RP, eds. Noise-induced Hearing Loss. St. Louis: Mosby-Year Book, 119–129.
  • Rajan R, Irvine DR, Wise LZ, Heil P. (1993). Effect of unilateral partial cochlear lesions in adult cats on the representation of lesioned and unlesioned cochleas in primary auditory cortex. J Comp Neurol 338:17–49.
  • Robertson D, Irvine RF. (1989). Plasticity of frequency organization in auditory cortex of Guinea pigs with partial unilateral deafness. J Comp Neurol 282:456–471.
  • Salvi RJ. (1976). Central components of the temporary threshold shift. In: Henderson D, Hamernik RP, Dosanjh DS, Mills JH, eds. Effects of Noise on Hearing. New York: Raven, 247–260.
  • Salvi RJ, Ahroon WA. (1983). Tinnitus and neural activity. J Speech Hear Res 26:629–632.
  • Sasaki CT, Babitz L, Kauer JS. (1981). Tinnitus: development of a neurophysiologic correlate. Laryngoscope 91:2018–2024.
  • Sasaki CT, Kauer JS, Babitz L. (1980). Differential [14C]2–deoxyglucose uptake after deafferentation of the mammalian auditory pathway—a model for examining tinnitus. Brain Res 194:511–516.
  • Schreiner CE, Snyder RL. (1987). A physiological animal model of tinnitus. Abs Assoc Res Otolaryngol 10:195.
  • Schreiner CE, Snyder RL, Lenarz TH. (1990). Spectral and temporal characteristics of abnormal ensemble spontaneous activity of cat auditory nerve. Abs Assoc Res Otolaryngol 13:197.
  • Shehata-Dieler WE, Richter CP, Dieler R, Klinke R. (1994). Effects of endolymphatic and perilymphatic application of salicylate in the pigeon. I: Single fiber activity and cochlear potentials. Hear Res 74:77–84.
  • Shulman A, Strashun AM, Afriyie M, Aronson F, Abel W, Goldstein B. (1995). SPECT imaging of brain and tinnitus—neurotologic/neurologic implications. Int Tinn J 1:13–29.
  • Sigalovsky I, Levine RA, Melcher JR, Guinan JJ, Talavage TM, Ravicz ME, Rosen BR, Benson RR, Fullerton BC. (1998). Tinnitus studies using functional magnetic resonance imaging: development of method. ARO Abs 21:51.
  • Smith DI, Lawrence Μ, Hawkins JE. (1985). Effects of noise and quinine on the vessels of the stria vascularis: an image analysis study. Am J Otolaryngol 6:280–289.
  • Stypulkowski PH. (1990). Mechanisms of salicylate ototoxicity. Hear Res 46:113–146.
  • Van Heusden E, Smoorenburg GF. (1983). Responses from AVON units in the cat before and after inducement of an acute noise trauma. Hear Res 11:295–326.
  • Vernon J. (1995). Tinnitus: cause, evaluation, and treatment. In: English GM, ed. Otolaryngology. Philadelphia: Lipponcott-Raven, 1–25.
  • Wallhauser-Franke E. (1997). Salicylate evokes c-fos expression in the brain stem: implications for tinnitus. Neuroreport 8:725–728.
  • Wazen JJ, Foyt D, Sisti M. (1997). Selective cochlear neurectomy for delibitating tinnitus. Ann Otol Rhinol Laryngol 106:568–570.
  • Zenner HP, Ernst A. (1995). Cochlear motor tinnitus, transduction tinnitus, and signal transfer tinnitus: three models of cochlear tinnitus. In: Vernon JA, Moller AR, eds. Mechanisms of Tinnitus. Boston: Allyn and Bacon, 237–254.
  • Zhang JS, Kaltenbach JA. (1998). Increases in spontaneous activity in the dorsal cochlear nucleus of the rat following exposure to high intensity sound. Neurosci Lett 250:197–200.
  • Zheng XY, Wang J, Salvi RJ, Henderson D. (1996). Effects of kainic acid on the cochlear potentials and distortion product otoacoustic emission in the chinchilla. Hear Res 95:161–167.