J Am Acad Audiol 2017; 28(08): 742-757
DOI: 10.3766/jaaa.16106
Articles
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Potential Audiological and MRI Markers of Tinnitus

Kamakshi V. Gopal§
*   Department of Audiology and Speech-Language Pathology, University of North Texas, Denton, TX
,
Binu P. Thomas§
†   Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX
,
Rajesh Nandy
‡   Biostatistics and Epidemiology, University of North Texas Health Science Center, Fort Worth, TX
,
Deng Mao
†   Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX
,
Hanzhang Lu
†   Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX
› Author Affiliations
Further Information

Publication History

Publication Date:
26 June 2020 (online)

Abstract

Background:

Subjective tinnitus, or ringing sensation in the ear, is a common disorder with no accepted objective diagnostic markers.

Purpose:

The purpose of this study was to identify possible objective markers of tinnitus by combining audiological and imaging-based techniques.

Research Design:

Case-control studies.

Study Sample:

Twenty adults drawn from our audiology clinic served as participants. The tinnitus group consisted of ten participants with chronic bilateral constant tinnitus, and the control group consisted of ten participants with no history of tinnitus. Each participant with tinnitus was closely matched with a control participant on the basis of age, gender, and hearing thresholds.

Data Collection and Analyses:

Data acquisition focused on systematic administration and evaluation of various audiological tests, including auditory-evoked potentials (AEP) and otoacoustic emissions, and magnetic resonance imaging (MRI) tests. A total of 14 objective test measures (predictors) obtained from audiological and MRI tests were subjected to statistical analyses to identify the best predictors of tinnitus group membership. The least absolute shrinkage and selection operator technique for feature extraction, supplemented by the leave-one-out cross-validation technique, were used to extract the best predictors. This approach provided a conservative model that was highly regularized with its error within 1 standard error of the minimum.

Results:

The model selected increased frontal cortex (FC) functional MRI activity to pure tones matching their respective tinnitus pitch, and augmented AEP wave N1 amplitude growth in the tinnitus group as the top two predictors of tinnitus group membership. These findings suggest that the amplified responses to acoustic signals and hyperactivity in attention regions of the brain may be a result of overattention among individuals that experience chronic tinnitus.

Conclusions:

These results suggest that increased functional MRI activity in the FC to sounds and augmented N1 amplitude growth may potentially be the objective diagnostic indicators of tinnitus. However, due to the small sample size and lack of subgroups within the tinnitus population in this study, more research is needed before generalizing these findings.

This research was supported by University of North Texas Faculty Research grants and the Once Upon a Time Foundation grant to KVG. This work was also partly supported by a grant from the National Institutes of Health, grant number R01 NS067015, to HL.


§ These authors contributed equally to this work.


 
  • REFERENCES

  • Adjamian P, Sereda M, Hall DA. 2009; The mechanisms of tinnitus: perspectives from human functional neuroimaging. Hear Res 253 1–2 15-31
  • American Tinnitus Association. (2016) Understanding the Facts. http://www.ata.org/understanding-facts
  • Anderer P, Pascual-Marqui RD, Semlitsch HV, Saletu B. 1998; Differential effects of normal aging on sources of standard N1, target N1 and target P300 auditory event-related brain potentials revealed by low resolution electromagnetic tomography (LORETA). Electroencephalogr Clin Neurophysiol 108 (02) 160-174
  • Arnold W, Bartenstein P, Oestreicher E, Römer W, Schwaiger M. 1996; Focal metabolic activation in the predominant left auditory cortex in patients suffering from tinnitus: a PET study with [18F]deoxyglucose. ORL 58 (04) 195-199
  • Aslan S, Lu H. 2010; On the sensitivity of ASL MRI in detecting regional differences in cerebral blood flow. Magn Reson Imaging 28 (07) 928-935
  • Attias J, Urbach D, Gold S, Shemesh Z. 1993; Auditory event related potentials in chronic tinnitus patients with noise induced hearing loss. Hear Res 71 1–2 106-113
  • 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 (01) 36-45
  • Burton H, Wineland A, Bhattacharya M, Nicklaus J, Garcia KS, Piccirillo JF. 2012; Altered networks in bothersome tinnitus: a functional connectivity study. BMC Neurosci 13 (03) 3
  • Cartocci G, Attanasio G, Fattapposta F, Locuratolo N, Mannarelli D, Filipo R. 2012; An electrophysiological approach to tinnitus interpretation. Int Tinnitus J 17 (02) 152-157
  • Chalela JA, Alsop DC, Gonzalez-Atavales JB, Maldjian JA, Kasner SE, Detre JA. 2000; Magnetic resonance perfusion imaging in acute ischemic stroke using continuous arterial spin labeling. Stroke 31 (03) 680-687
  • Chen YC, Xia W, Feng Y, Li X, Zhang J, Feng X, Wang CX, Cai Y, Wang J, Salvi R, Teng GJ. 2015; Altered interhemispheric functional coordination in chronic tinnitus patients. BioMed Res Int 2015: 345647
  • De Ridder D, Song JJ, Vanneste S. 2013; Frontal cortex TMS for tinnitus. Brain Stimulat 6 (03) 355-362
  • Eggermont JJ. 2006; Cortical tonotopic map reorganization and its implications for treatment of tinnitus. Acta Otolaryngol Suppl 126 (556, Suppl) 9-12
  • Eggermont JJ. 2013; Hearing loss, hyperacusis, or tinnitus: what is modeled in animal research?. Hear Res 295: 140-149
  • Eggermont JJ. 2015; The auditory cortex and tinnitus—a review of animal and human studies. Eur J Neurosci 41 (05) 665-676
  • Eggermont JJ, Roberts LE. 2004; The neuroscience of tinnitus. Trends Neurosci 27 (11) 676-682
  • Gaab N, Gaser C, Zaehle T, Jancke L, Schlaug G. 2003; Functional anatomy of pitch memory—an fMRI study with sparse temporal sampling. Neuroimage 19 (04) 1417-1426
  • Gallinat J, Mulert C, Bajbouj M, Herrmann WM, Schunter J, Senkowski D, Moukhtieva R, Kronfeldt D, Winterer G. 2002; Frontal and temporal dysfunction of auditory stimulus processing in schizophrenia. Neuroimage 17 (01) 110-127
  • Giard MH, Perrin F, Echallier JF, Thévenet M, Froment JC, Pernier J. 1994; Dissociation of temporal and frontal components in the human auditory N1 wave: a scalp current density and dipole model analysis. Electroencephalogr Clin Neurophysiol 92 (03) 238-252
  • Gopal KV, Bishop CE, Carney L. 2004; Auditory measures in clinically depressed individuals. II. Auditory evoked potentials and behavioral speech tests. Int J Audiol 43 (09) 499-505
  • Gopal KV, Thomas BP, Mao D, Lu H. 2015; Efficacy of carnitine in treatment of tinnitus: evidence from audiological and MRI measures—a case study. J Am Acad Audiol 26 (03) 311-324
  • Gu JW, Halpin CF, Nam EC, Levine RA, Melcher JR. 2010; Tinnitus, diminished sound-level tolerance, and elevated auditory activity in humans with clinically normal hearing sensitivity. J Neurophysiol 104 (06) 3361-3370
  • Gu JW, Herrmann BS, Levine RA, Melcher JR. 2012; Brainstem auditory evoked potentials suggest a role for the ventral cochlear nucleus in tinnitus. J Assoc Res Otolaryngol 13 (06) 819-833
  • Haller S, Birbaumer N, Veit R. 2010; Real-time fMRI feedback training may improve chronic tinnitus. Eur Radiol 20 (03) 696-703
  • Heeren A, Maurage P, Perrot H, De Volder A, Renier L, Araneda R, Lacroix E, Decat M, Deggouj N, Philippot P. 2014; Tinnitus specifically alters the top-down executive control sub-component of attention: evidence from the Attention Network Task. Behav Brain Res 269: 147-154
  • Heinrichs-Graham E, Franzen JD, Knott NL, White ML, Wetzel MW, Wilson TW. 2014; Pharmaco-MEG evidence for attention related hyper-connectivity between auditory and prefrontal cortices in ADHD. Psychiatry Res 221 (03) 240-245
  • Henry JA, McMillan GP, Thielman EJ, Galvez G, Zaugg TL, Porsov E, Silaski G. 2013; Evaluating psychoacoustic measures for establishing presence of tinnitus. J Rehabil Res Dev 50 (04) 573-584
  • Husain FT. (2016) Neural networks of tinnitus in human: elucidating severity and habituation. Hear Res 334:37–48. doi: 10.1016/j.heares.2015.09.010
  • Ikner CL, Hassen AH. 1990; The effect of tinnitus on ABR latencies. Ear Hear 11 (01) 16-20
  • 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 1–2 66-74
  • Kadner A, Viirre E, Wester DC, Walsh SF, Hestenes J, Vankov A, Pineda JA. 2002; Lateral inhibition in the auditory cortex: an EEG index of tinnitus?. Neuroreport 13 (04) 443-446
  • Kaltenbach JA, Rachel JD, Mathog TA, Zhang J, Falzarano PR, Lewandowski M. 2002; Cisplatin-induced hyperactivity in the dorsal cochlear nucleus and its relation to outer hair cell loss: relevance to tinnitus. J Neurophysiol 88 (02) 699-714
  • Kaltenbach JA, Zhang J, Zacharek MA. 2004. Neural correlates of tinnitus. In: Snow JB. Tinnitus: Theory and Management. London: BC Decker Inc; 141-161
  • Kehrle HM, Granjeiro RC, Sampaio AL, Bezerra R, Almeida VF, Oliveira CA. 2008; Comparison of auditory brainstem response results in normal-hearing patients with and without tinnitus. Arch Otolaryngol Head Neck Surg 134 (06) 647-651
  • Knipper M, Van Dijk P, Nunes I, Rüttiger 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
  • Langguth B, Landgrebe M, Kleinjung T, Sand GP, Hajak G. 2011; Tinnitus and depression. World J Biol Psychiatry 12 (07) 489-500
  • Lanting CP, de Kleine E, van Dijk P. 2009; Neural activity underlying tinnitus generation: results from PET and fMRI. Hear Res 255 1–2 1-13
  • Leaver AM, Renier L, Chevillet MA, Morgan S, Kim HJ, Rauschecker JP. 2011; Dysregulation of limbic and auditory networks in tinnitus. Neuron 69 (01) 33-43
  • Leaver AM, Seydell-Greenwald A, Turesky TK, Morgan S, Kim HJ, Rauschecker JP. 2012; Cortico-limbic morphology separates tinnitus from tinnitus distress. Front Syst Neurosci 6: 21
  • 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
  • Lemaire MC, Beutter P. 1995; Brainstem auditory evoked responses in patients with tinnitus. Audiology 34 (06) 287-300
  • Liu XP, Chen L. 2012; Auditory brainstem response as a possible objective indicator for salicylate-induced tinnitus in rats. Brain Res 1485: 88-94
  • 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 (01) 114-120
  • Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH. (2003) An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 19:1233–1239.
  • Maurizi M, Ottaviani F, Paludetti G, Almadori G, Tassoni A. 1985; Contribution to the differentiation of peripheral versus central tinnitus via auditory brain stem response evaluation. Audiology 24 (03) 207-216
  • McKee GJ, Stephens SDG. 1992; An investigation of normally hearing subjects with tinnitus. Audiology 31 (06) 313-317
  • Melcher JR, Levine RA, Bergevin C, Norris B. 2009; The auditory midbrain of people with tinnitus: abnormal sound-evoked activity revisited. Hear Res 257 1–2 63-74
  • Melcher JR, Sigalovsky IS, Guinan Jr JJ, Levine RA. 2000; Lateralized tinnitus studied with functional magnetic resonance imaging: abnormal inferior colliculus activation. J Neurophysiol 83 (02) 1058-1072
  • Mirz F, Gjedde A, Ishizu K, Pedersen CB. 2000; Cortical networks subserving the perception of tinnitus—a PET study. Acta Otolaryngol 120: 241-243
  • Mirz F, Pedersen B, Ishizu K, Johannsen P, Ovesen T, Stødkilde-Jørgensen H, Gjedde A. 1999; Positron emission tomography of cortical centers of tinnitus. Hear Res 134 1–2 133-144
  • Muhlnickel W, Elbert T, Taub E, Flor H. (1998) Reorganization of auditory cortex in tinnitus. Proc Natl Acad Sci USA 95:10340–10343. doi: 10.1073/pnas.95.17.10340
  • Newman CW, Jacobson GP, Spitzer JB. 1996; Development of the tinnitus handicap inventory. Arch Otolaryngol Head Neck Surg 122 (02) 143-148
  • Noreña AJ, Eggermont JJ. 2003; Changes in spontaneous neural activity immediately after an acoustic trauma: implications for neural correlates of tinnitus. Hear Res 183 1–2 137-153
  • Paul BT, Bruce IC, Bosnyak DJ, Thompson DC, Roberts LE. 2014; Modulation of electrocortical brain activity by attention in individuals with and without tinnitus. Neural Plast 2014: 127824
  • Picton TW, Alain C, Woods DL, John MS, Scherg M, Valdes-Sosa P, Bosch-Bayard J, Trujillo NJ. 1999; Intracerebral sources of human auditory-evoked potentials. Audiol Neurootol 4 (02) 64-79
  • Rauschecker JP, Leaver AM, Mühlau M. 2010; Tuning out the noise: limbic-auditory interactions in tinnitus. Neuron 66 (06) 819-826
  • Roberts LE, Bosnyak DJ, Thompson DC. 2012; Neural plasticity expressed in central auditory structures with and without tinnitus. Front Syst Neurosci 6: 40
  • Roberts LE, Husain FT, Eggermont JJ. 2013; Role of attention in the generation and modulation of tinnitus. Neurosci Biobehav Rev 37 (08) 1754-1773
  • Rosburg T, Trautner P, Dietl T, Korzyukov OA, Boutros NN, Schaller C, Elger CE, Kurthen M. 2005; Subdural recordings of the mismatch negativity (MMN) in patients with focal epilepsy. Brain 128 (04) 819-828
  • Rossi AF, Pessoa L, Desimone R, Ungerleider LG. 2009; The prefrontal cortex and the executive control of attention. Exp Brain Res 192 (03) 489-497
  • Santos Filha VA, Matas CG. 2010; Late auditory evoked potentials in individuals with tinnitus. Rev Bras Otorrinolaringol (Engl Ed) 76 (02) 263-270
  • Schaette R. 2014; Tinnitus in men, mice (as well as other rodents), and machines. Hear Res 311: 63-71
  • Schaette R, McAlpine D. 2011; Tinnitus with a normal audiogram: physiological evidence for hidden hearing loss and computational model. J Neurosci 31 (38) 13452-13457
  • Schlee W, Mueller N, Hartmann T, Keil J, Lorenz I, Weisz N. 2009; Mapping cortical hubs in tinnitus. BMC Biol 7 (01) 80
  • Seki S, Eggermont JJ. 2003; Changes in spontaneous firing rate and neural synchrony in cat primary auditory cortex after localized tone-induced hearing loss. Hear Res 180 1–2 28-38
  • 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
  • Shulman A, Seitz MR. 1981; Central tinnitus—diagnosis and treatment. Observations simultaneous binaural auditory brain responses with monaural stimulation in the tinnitus patient. Laryngoscope 91 (12) 2025-2035
  • Szczepek AJ, Haupt H, Klapp BF, Olze H, Mazurek B. 2014; Biological correlates of tinnitus-related distress: an exploratory study. Hear Res 318: 23-30
  • Tibshirani R. 1996; Regression shrinkage and selection via the lasso. J R Stat Soc B 58 (01) 267-288
  • Tung KC, Uh J, Mao D, Xu F, Xiao G, Lu H. 2013; Alterations in resting functional connectivity due to recent motor task. Neuroimage 78: 316-324
  • Vernon JA, Meikle MB. 2003; Tinnitus: clinical measurement. Otolaryngol Clin North Am 36 (02) 293-305, vi
  • Walpurger V, Hebing-Lennartz G, Denecke H, Pietrowsky R. 2003; Habituation deficit in auditory event-related potentials in tinnitus complainers. Hear Res 181 1–2 57-64
  • Wang J, Alsop DC, Song HK, Maldjian JA, Tang K, Salvucci AE, Detre JA. 2003; Arterial transit time imaging with flow encoding arterial spin tagging (FEAST). Magn Reson Med 50 (03) 599-607
  • Wilson PH, Henry J, Bowen M, Haralambous G. 1991; Tinnitus reaction questionnaire: psychometric properties of a measure of distress associated with tinnitus. J Speech Hear Res 34 (01) 197-201
  • Wu C, Gopal K, Gross GW, Lukas TJ, Moore EJ. 2011; An in vitro model for testing drugs to treat tinnitus. Eur J Pharmacol 667 1–3 188-194
  • Xu F, Uh J, Brier MR, Hart Jr J, Yezhuvath US, Gu H, Yang Y, Lu H. 2011; The influence of carbon dioxide on brain activity and metabolism in conscious humans. J Cereb Blood Flow Metab 31 (01) 58-67
  • Zhang F, Deshpande A, Benson C, Smith M, Eliassen J, Fu QJ. 2011; The adaptive pattern of the auditory N1 peak revealed by standardized low-resolution brain electromagnetic tomography. Brain Res 1400: 42-52