Human Brain Imaging of Tinnitus and Animal Models

ABSTRACT

Because subjective tinnitus is typically localized to the ear with hearing loss, tinnitus was traditionally thought to originate from neural hyperactivity in the damaged ear. However, most studies have found that hearing loss reduces the neural outputs from the damaged cochlea. These negative findings led to the hypothesis that tinnitus arises from aberrant neural activity in the central auditory system. Positron emission tomography imaging studies performed on tinnitus patients that could modulate their tinnitus provide evidence showing that the aberrant neural activity that gives rise to tinnitus resides in the central auditory pathway. To investigate the biological basis of tinnitus in more detail, an animal model was developed that allowed behavioral measures of tinnitus to be obtained from individual rats after inducing tinnitus with high doses of salicylate or high-intensity noise. This behavioral model was used to test the efficacy of memantine, an N-methyl-D-aspartate antagonist, and scopolamine, an anticholinergic, in suppressing salicylate-induced tinnitus. Neither drug completely suppressed salicylate-induced tinnitus. To detect the physiological changes associated with tinnitus, chronic microwire electrodes were implanted in the auditory cortex and measurements were obtained from the auditory cortex before and after salicylate and noise exposures known to induce tinnitus. High doses of salicylate or high-level noise exposure generally resulted in sound-evoked hyperactivity in the electrophysiological responses recorded from the auditory cortex of awake-animals. However, anesthetic tended to suppress or abolish the hyperactivity.

Tinnitus - salicylate - noise exposure - auditory cortex - spontaneous activity - positron emission tomography

REFERENCES

• 1 Atherley G R, Hempstock T I, Noble W G. Study of tinnitus induced temporarily by noise.  J Acoust Soc Am. 1968;  44(6) 1503-1506
• 2 Myers E N, Bernstein J M. Salicylate ototoxicity; a clinical and experimental study.  Arch Otolaryngol. 1965;  82(5) 483-493
• 3 Muller M, Klinke R, Arnold W, Oestreicher E. Auditory nerve fibre responses to salicylate revisited.  Hear Res. 2003;  183(1–2) 37-43
• 4 Dallos P, Harris D. Properties of auditory nerve responses in absence of outer hair cells.  J Neurophysiol. 1978;  41(2) 365-383
• 5 Kiang N YS, Moxon E C, Levine R A. Auditory-nerve activity in cats with normal and abnormal cochleas. In: Wolstenholme GEW, Knight J Sensorineural Hearing Loss. London, UK; J & A Churchill 1970: 241-273
• 6 Wang J, Powers N L, Hofstetter P et al.. Effects of selective inner hair cell loss on auditory nerve fiber threshold, tuning and spontaneous and driven discharge rate.  Hear Res. 1997;  107(1–2) 67-82
• 7 Liberman M C, Dodds L W. Single-neuron labeling and chronic cochlear pathology. II. Stereocilia damage and alterations of spontaneous discharge rates.  Hear Res. 1984;  16(1) 43-53
• 8 House J W, Brackmann D E. Tinnitus: surgical treatment.  Ciba Found Symp. 1981;  85 204-216
• 9 Coad M L, Lockwood A, Salvi R, Burkard R. Characteristics of patients with gaze-evoked tinnitus.  Otol Neurotol. 2001;  22(5) 650-654
• 10 Lockwood A H, Wack D S, Burkard R F et al.. The functional anatomy of gaze-evoked tinnitus and sustained lateral gaze.  Neurology. 2001;  56(4) 472-480
• 11 Salvi R J, Saunders S S, Gratton M A, Arehole S, Powers N. Enhanced evoked response amplitudes in the inferior colliculus of the chinchilla following acoustic trauma.  Hear Res. 1990;  50 245-258
• 12 Qiu C, Salvi R, Ding D, Burkard R. Inner hair cell loss leads to enhanced response amplitudes in auditory cortex of unanesthetized chinchillas: evidence for increased system gain.  Hear Res. 2000;  139(1–2) 153-171
• 13 Salvi R J, Wang J, Ding D. Auditory plasticity and hyperactivity following cochlear damage.  Hear Res. 2000;  147(1–2) 261-274
• 14 Levine R A, Abel M, Cheng H. CNS somatosensory-auditory interactions elicit or modulate tinnitus.  Exp Brain Res. 2003;  153(4) 643-648
• 15 Sanchez T G, da Silva Lima A, Brandao A L, Lorenzi M C, Bento R F. Somatic modulation of tinnitus: test reliability and results after repetitive muscle contraction training.  Ann Otol Rhinol Laryngol. 2007;  116(1) 30-35
• 16 Lockwood A H, Salvi R J, Coad M L et al.. The functional neuroanatomy of tinnitus: evidence for limbic system links and neural plasticity.  Neurology. 1998;  50(1) 114-120
• 17 Hallam R, Rachman S, Hinchcliffe R. Psychological aspects of tinnitus. In: Rachman S Contributions to Medical Psychology. Oxford, UK; Pergamon Press 1984: 31-53
• 18 Jastreboff P J, Gray W C, Gold S L. Neurophysiological approach to tinnitus patients.  Am J Otol. 1996;  17(2) 236-240
• 19 Illing R B, Horvath M. Re-emergence of GAP-43 in cochlear nucleus and superior olive following cochlear ablation in the rat.  Neurosci Lett. 1995;  194(1–2) 9-12
• 20 Irvine D R, Rajan R, Smith S. Effects of restricted cochlear lesions in adult cats on the frequency organization of the inferior colliculus.  J Comp Neurol. 2003;  467(3) 354-374
• 21 Vasama J P, Marttila T, Lahin T, Makela J P. Auditory pathway function after vestibular schwannoma surgery.  Acta Otolaryngol. 2001;  121(3) 378-383
• 22 Harrison R V, Ibrahim D, Mount R J. Plasticity of tonotopic maps in auditory midbrain following partial cochlear damage in the developing chinchilla.  Exp Brain Res. 1998;  123(4) 449-460
• 23 Salvi R J, Ding D, Wang J, McFadden S L, Sun W. Functional changes in peripheral and central auditory pathways following selective inner hair cell loss.  Semin Hear. 2003;  24 135-146
• 24 Otsuka K, Pulec J L, Suzuki M. Assessment of intravenous lidocaine for the treatment of subjective tinnitus.  Ear Nose Throat J. 2003;  82(10) 781-784
• 25 Rudack C, Hillebrandt M, Wagenmann M, Hauser U. Treatment of tinnitus with lidocaine? A report of clinical experiences.  HNO. 1997;  45(2) 69-73
• 26 Schwab B, Lenarz T, Heermann R. Use of the round window micro cath for inner ear therapy—results of a placebo-controlled, prospective study on chronic tinnitus.  Laryngorhinootologie. 2004;  83(3) 164-172
• 27 Baguley D M, Jones S, Wilkins I, Axon P R, Moffat D A. The inhibitory effect of intravenous lidocaine infusion on tinnitus after translabyrinthine removal of vestibular schwannoma: a double-blind, placebo-controlled, crossover study.  Otol Neurotol. 2005;  26(2) 169-176
• 28 Reyes S A, Salvi R J, Burkard R F et al.. Brain imaging of the effects of lidocaine on tinnitus.  Hear Res. 2002;  171(1–2) 43-50
• 29 Hargarten K, Chapman P D, Stueven H A et al.. Prehospital prophylactic lidocaine does not favorably affect outcome in patients with chest pain.  Ann Emerg Med. 1990;  19(11) 1274-1279
• 30 Murai K, Tyler R S, Harker L A, Stouffer J L. Review of pharmacologic treatment of tinnitus.  Am J Otol. 1992;  13(5) 454-464
• 31 Lobarinas E, Sun W, Cushing R, Salvi R. A novel behavioral paradigm for assessing tinnitus using schedule-induced polydipsia avoidance conditioning (SIP-AC).  Hear Res. 2004;  190(1–2) 109-114
• 32 Mongan E, Kelly P, Nies K, Porter W W, Paulus H E. Tinnitus as an indication of therapeutic serum salicylate levels.  JAMA. 1973;  226(2) 142-145
• 33 Jastreboff P J, Brennan J F, Sasaki C T. An animal model for tinnitus.  Laryngoscope. 1988;  98(3) 280-286
• 34 Oestreicher E, Arnold W, Ehrenberger K, Felix D. Memantine suppresses the glutamatergic neurotransmission of mammalian inner hair cells.  ORL J Otorhinolaryngol Relat Spec. 1998;  60(1) 18-21
• 35 Lin X. Action potentials and underlying voltage-dependent currents studied in cultured spiral ganglion neurons of the postnatal gerbil.  Hear Res. 1997;  108(1-2) 157-179
• 36 Guitton M J, Caston J, Ruel J et al.. Salicylate induces tinnitus through activation of cochlear NMDA receptors.  J Neurosci. 2003;  23(9) 3944-3952
• 37 Lobarinas E, Yang G, Sun W et al.. Salicylate- and quinine-induced tinnitus and effects of memantine.  Acta Otolaryngol Suppl. 2006;  (556) 13-19
• 38 Wallhausser-Franke E, Cuautle-Heck B, Wenz G, Langner G, Mahlke C. Scopolamine attenuates tinnitus-related plasticity in the auditory cortex.  Neuroreport. 2006;  17(14) 1487-1491
• 39 Heffner H E, Harrington I A. Tinnitus in hamsters following exposure to intense sound.  Hear Res. 2002;  170(1–2) 83-95
• 40 Loeb M, Smith R. Relation of induced tinnitus to physical characteristics of the inducing stimuli.  J Acoust Soc Am. 1967;  42 453-455
• 41 Zurita P, Villa A E, de Ribaupierre Y, de Ribaupierre F, Rouiller E M. Changes of single unit activity in the cat's auditory thalamus and cortex associated to different anesthetic conditions.  Neurosci Res. 1994;  19(3) 303-316
• 42 Astl J, Popelar J, Kvasnak E, Syka J. Comparison of response properties of neurons in the inferior colliculus of guinea pigs under different anesthetics.  Audiology. 1996;  35(6) 335-345
• 43 Anderson M J, Young E D. Isoflurane/N2O anesthesia suppresses narrowband but not wideband inhibition in dorsal cochlear nucleus.  Hear Res. 2004;  188(1–2) 29-41
• 44 Yang G, Lobarinas E, Zhang L et al.. Salicylate induced tinnitus: behavioral measures and neural activity in auditory cortex of awake rats.  Hear Res. 2007;  226(1–2) 244-253
• 45 Gaese B H, Ostwald J. Anesthesia changes frequency tuning of neurons in the rat primary auditory cortex.  J Neurophysiol. 2001;  86(2) 1062-1066
• 46 Verbny Y I, Merriam E B, Banks M I. Modulation of gamma-aminobutyric acid type A receptor-mediated spontaneous inhibitory postsynaptic currents in auditory cortex by midazolam and isoflurane.  Anesthesiology. 2005;  102(5) 962-969
• 47 Axelsson A, Prasher D. Tinnitus induced by occupational and leisure noise.  Noise Health. 2000;  2(8) 47-54
• 48 Weisz N, Wienbruch C, Dohrmann K, Elbert T. Neuromagnetic indicators of auditory cortical reorganization of tinnitus.  Brain. 2005;  128(Pt 11) 2722-2731
• 49 Cacace A T, Lovely T J, Winter D F, Parnes S M, McFarland D J. Auditory perceptual and visual-spatial characteristics of gaze-evoked tinnitus.  Audiology. 1994;  33(5) 291-303
• 50 Ashton H, Reid K, Marsh R et al.. High frequency localised “hot spots” in temporal lobes of patients with intractable tinnitus: a quantitative electroencephalographic (QEEG) study.  Neurosci Lett. 2007;  426(1) 23-28
• 51 Pockett S. Anesthesia and the electrophysiology of auditory consciousness.  Conscious Cogn. 1999;  8(1) 45-61
• 52 Jastreboff P J, Sasaki C T. Salicylate-induced changes in spontaneous activity of single units in the inferior colliculus of the guinea pig.  J Acoust Soc Am. 1986;  80(5) 1384-1391
• 53 Chen G D, Jastreboff P J. Salicylate-induced abnormal activity in the inferior colliculus of rats.  Hear Res. 1995;  82(2) 158-178
• 54 Eggermont J J, Kenmochi M. Salicylate and quinine selectively increase spontaneous firing rates in secondary auditory cortex.  Hear Res. 1998;  117(1–2) 149-160
• 55 Zhang J S, Kaltenbach J A. Increases in spontaneous activity in the dorsal cochlear nucleus of the rat following exposure to high-intensity sound.  Neurosci Lett. 1998;  250(3) 197-200
• 56 Cheung S W, Nagarajan S S, Bedenbaugh P H et al.. Auditory cortical neuron response differences under isoflurane versus pentobarbital anesthesia.  Hear Res. 2001;  156(1–2) 115-127