Tinnitus is characterized by the perception of sound in the absence of an external auditory stimulus. The network connectivity of auditory and non-auditory brain structures associated with emotion, memory and attention are functionally altered in debilitating tinnitus. Current studies suggest that tinnitus results from neuroplastic changes in the frontal and limbic temporal regions. The objective of this study was to use Single-Photon Emission Computed Tomography (SPECT) to evaluate changes in the cerebral blood flow in tinnitus patients with normal hearing compared with healthy controls. Methods: Twenty tinnitus patients with normal hearing and 17 healthy controls, matched for sex, age and years of education, were subjected to Single Photon Emission Computed Tomography using the radiotracer ethylenedicysteine diethyl ester, labeled with Technetium 99 m (99 mTc-ECD SPECT). The severity of tinnitus was assessed using the “Tinnitus Handicap Inventory” (THI). The images were processed and analyzed using “Statistical Parametric Mapping” (SPM8). Results: A significant increase in cerebral perfusion in the left parahippocampal gyrus (pFWE <0.05) was observed in patients with tinnitus compared with healthy controls. The average total THI score was 50.8+18.24, classified as moderate tinnitus. Conclusion: It was possible to identify significant changes in the limbic system of the brain perfusion in tinnitus patients with normal hearing, suggesting that central mechanisms, not specific to the auditory pathway, are involved in the pathophysiology of symptoms, even in the absence of clinically diagnosed peripheral changes.
References
[1]
Eggermont JJ, Roberts LE (2004) The neuroscience of tinnitus. TRENDS in Neurosciences 27(11): 676–682. doi: 10.1016/j.tins.2004.08.010
[2]
Jastreboff PJ (1990) Phantom auditory perception (tinnitus): mechanisms of generation and perception. Neurosci Res 8: 221–254. doi: 10.1016/0168-0102(90)90031-9
[3]
Gardner A, Pagani M, Jacobsson H, Lindberg G, Larsson SA, et al. (2002) Differences in resting state regional cerebral blood flow assessed with 99mTc-HMPAO SPECT and brain atlas matching between depressed patients with and without tinnitus. Nuclear Medicine Communications 23: 429–439. doi: 10.1097/00006231-200205000-00002
[4]
Vanneste S, De Ridder D (2012) The auditory and non-auditory brain areas involved in tinnitus. An emergent property of multiple parallel overlapping subnetworks. Front Syst Neurosci 6: 31. doi: 10.3389/fnsys.2012.00031
[5]
Nore?a AJ, Farley BJ (2013) Tinnitus-related neural activity: theories of generation, propagation, and centralization. Hear Res 295: 161–171. doi: 10.1016/j.heares.2012.09.010
[6]
Balkenhol T, Wallh?usser-Franke E, Delb W (2013) Psychoacoustic tinnitus loudness and tinnitus-related distress show different associations with oscillatory brain activity. PLoS One 8(1): e53180. doi: 10.1371/journal.pone.0053180
[7]
Eggermont JJ (2006) Cortical tonotopic map reorganization and its implications for treatment of tinnitus. Acta Otolaryngol Suppl 556: 9–12. Review.
[8]
Baizer JS, Lobarinas E, Salvi R, Allman BL (2012) Brain Research special issue: advances in the neuroscience of tinnitus. Brain Res 1485: 1–2. doi: 10.1016/j.brainres.2012.10.033
[9]
Leaver AM, Renier L, Chevillet MA, Morgan S, Kim HJ, et al. (2011) Dysregulation of limbic and auditory networks in tinnitus. Neuron 69(1): 33–43. doi: 10.1016/j.neuron.2010.12.002
[10]
Maudoux A, Lefebvre P, Cabay JE, Demertzi A, Vanhaudenhuyse A, et al. (2012) Auditory resting-state network connectivity in tinnitus: a functional MRI study. PLoS One7(5): e36222. doi: 10.1371/journal.pone.0036222
[11]
Schlee W, Weisz N, Bertrand O, Hartmann T, Elbert T (2008) Using auditory steady state responses to outline the functional connectivity in the tinnitus brain. PLoS One 3(11): e3720. doi: 10.1371/journal.pone.0003720
[12]
De Ridder D, Vanneste S, Weisz N, Londero A, Schlee W, et al.. (2013) An integrative model of auditory phantom perception: Tinnitus as a unified percept of interacting separable subnetworks. Neurosci Biobehav Rev. pii: S0149–7634 (13) 00081-X.
[13]
Langguth B, Schecklmann M, Lehner A, Landgrebe M, Poeppl TB, et al. (2012) Neuroimaging and neuromodulation: complementary approaches for identifying the neuronal correlates of tinnitus. Front Syst Neurosci 6: 15. doi: 10.3389/fnsys.2012.00015
[14]
Farhadi M, Mahmoudian S, Saddadi F, Karimian AR, Mirzaee M, et al. (2010) Functional brain abnormalities localized in 55 chronic tinnitus patients: fusion of SPECT coincidence imaging and MRI. Journal of Cerebral Blood Flow & Metabolism 30: 864–870. doi: 10.1038/jcbfm.2009.254
[15]
Schaette R, McAlpine D (2011) Tinnitus with a Normal Audiogram: Physiological Evidence for Hidden Hearing Loss and Computational Model. The Journal of Neuroscience 31(38): 13452–13457. doi: 10.1523/jneurosci.2156-11.2011
[16]
Sataloff RT, Mandel S, Muscal E, Park CH, Rosen DC, et al. (1996) Single-photon-emission computed tomography (SPECT) in neurotologic assessment: a preliminary report. Am J Otol 17(6): 909–916.
[17]
Ferreira PA, Cunha F, Onishi ET, Branco-Barreiro FCA, Ganan?a FF (2005) Tinnitus handicap inventory: adapta??o cultural para o Português brasileiro. Pró-Fono R Atual Cient 17: 277–280. doi: 10.1590/s0104-56872005000300004
[18]
Newman CW, Jacobson GP, Spitzer JB (1996) Development of the tinnitus handicap inventory. Arch Otolaryngol Head Neck Surg 122: 143–148. doi: 10.1001/archotol.1996.01890140029007
[19]
McCombe A, Bagueley D, Coles R, McKenna L, McKinney C, et al. (2001) Guidelines for the grading of tinnitus severity : the results of a working group commissioned by the British Association of Otolaryngologists, Head and Neck Surgeons, 1999. Clin Otolaryngol 26: 388–393. doi: 10.1046/j.1365-2273.2001.00490.x
Morbelli S, Rodriguez G, Mignone A, Altrinetti V, Brugnolo A, et al. (2008) The need of appropriate brain SPECT templates for SPM comparisons (2008) Q J Nucl Med Mol Imaging. 52(1): 89–98.
[22]
Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, et al. (2002) Automated Anatomical Labeling of activations in SPM using a Macroscopic Anatomical Parcellation of the MNI MRI single-subject brain. NeuroImage 15(1): 273–289. doi: 10.1006/nimg.2001.0978
[23]
Shulman A, Strashun AM, Afriyie M, Aronson F, Abel W, et al. (1995) SPECT Imaging of Brain and Tinnitus-Neurotologic/Neurologic Implications. Int Tinnitus J 1(1): 13–29.
[24]
Staffen W, Biesinger E, Trinka E, Ladurner G (1999) The effect of lidocaine on chronic tinnitus: a quantitative cerebral perfusion study. Audiology 38(1): 53–57. doi: 10.3109/00206099909073002
[25]
Shulman A, Strashun AM, Seibyl JP, Daftary A, Goldstein B (2000) Benzodiazepine receptor deficiency and tinnitus. Int Tinnitus J 6(2): 98–111.
[26]
Shulman A, Strashun AM, Goldstein BA (2002) GABAA-benzodiazepine-chloride receptor-targeted therapy for tinnitus control: preliminary report. Int Tinnitus J 8(1): 30–36.
[27]
Shulman A, Goldstein B (2006) Brain and inner-ear fluid homeostasis, cochleovestibular-type tinnitus, and secondary endolymphatic hydrops. Int Tinnitus J 12(1): 75–81.
[28]
Shulman A, Goldstein B, Strashun AM (2007) Central nervous system neurodegeneration and tinnitus: a clinical experience. Part I: Diagnosis. Int Tinnitus J 13(2): 118–131.
[29]
Marcondes RA, Sanchez TG, Kii MA, Ono CR, Buchpiguel CA, et al. (2010) Repetitive transcranial magnetic stimulation improve tinnitus in normal hearing patients: a double-blind controlled, clinical and neuroimaging outcome study. Eur J Neurol 17(1): 38–44. doi: 10.1111/j.1468-1331.2009.02730.x
[30]
Mahmoudian S, Farhadi M, Gholami S, Saddadi F, Karimian AR, et al. (2012) Pattern of brain blood perfusion in tinnitus patients using technetium-99m SPECT imaging. J Res Med Sci 17(3): 242–247.
[31]
Weisz N, Dohrmann K, Elbert T (2007) The relevance of spontaneous activity for the coding of the tinnitus sensation. Prog Brain Res 166: 61–70. doi: 10.1016/s0079-6123(07)66006-3
[32]
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(5): 715–731. doi: 10.1007/s10162-012-0340-5
[33]
Lockwood AH, Salvi RJ, Coad ML, Towsley ML, Wack DS, et al. (1998) The functional neuroanatomy of tinnitus: evidence for limbic system links and neural plasticity. Neurology 50(1): 114–20. doi: 10.1212/wnl.50.1.114
[34]
Jastreboff PJ, Jastreboff MM (2000) Tinnitus Retraining Therapy (TRT) as a method for treatment of tinnitus and hyperacusis patients. J Am Acad Audiol 11(3): 162–77. doi: 10.1016/s0079-6123(07)66040-3
[35]
Joos K, Vanneste S, De Ridder D (2012) Disentangling depression and distress networks in the tinnitus brain. PLoS One 7(7): e40544. doi: 10.1371/journal.pone.0040544
[36]
De Ridder D, Fransen H, Francois O, Sunaert S, Kovacs S, et al. (2006) Amygdalohippocampal involvement in tinnitus and auditory memory. Acta OtoLaryngologica 126: 50–53. doi: 10.1080/03655230600895580
[37]
De Ridder D, Elgoyhen AB, Romo R, Langguth B (2011) Phantom percepts: tinnitus and pain as persisting aversive memory networks. Proc.Natl.Acad.Sci 108: 8075–8080. doi: 10.1073/pnas.1018466108
[38]
Gosselin N, Samson S, Adolphs R, Noulhiane M, Roy M, et al. (2006) Emotional responses to unpleasant music correlates with damage to the parahippocampal cortex. Brain 129(Pt 10): 2585–2592. doi: 10.1093/brain/awl240
[39]
McNaughton N, Corr PJ (2004) A two-dimensional neuropsychology of defense: fear/anxiety and defensive distance. Neurosci Biobehav Rev 28: 282–305. doi: 10.1016/j.neubiorev.2004.03.005
[40]
Rauschecker JP, Leaver AM, Mühlau M (2010) Tuning out the noise: limbic-auditory interactions in tinnitus. Neuron 66(6): 819–26. doi: 10.1016/j.neuron.2010.04.032