{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:12:44Z","timestamp":1777925564629,"version":"3.51.4"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Audiology Research"],"abstract":"<jats:p>Background\/Objectives: In the early stage of presbycusis, patients experience reduced speech perception in noisy environments despite normal audiometry, normally known as hidden hearing loss. Diagnostic indicators like the reduced amplitude of ABR wave I, elevated extended high-frequency threshold (EHT), and decreased middle ear muscle reflex (MEMR) amplitude aim to identify biomarkers of peripheral auditory pathology but remain inconsistent. Mismatch negativity (MMN) is a cortical auditory evoked potential generated when the brain detects sound changes. This study aimed to assess MMN as a diagnostic tool for hidden hearing loss in adults. Methods: Seventy-three subjects with normal hearing underwent an extended pure-tone audiogram examination ranging from 0.125 to 16 kHz and a subsequent MMN assessment with two different paradigms: a speech (ba\/da) and a tone (1\/2 kHz) paradigm. The MMN\u2019s amplitude and latency were measured and analyzed. Results: The outcome shows a significant age-related effect on MMN amplitude in the speech condition (\u03c7\u00b2 = 13.0, p = 0.002). Specifically, the MMN amplitude in the 25\u201330-year-old group was significantly smaller than in the 20\u201325-year-old group (p = 0.0015, Cohen\u2019s d = 0.63). Additionally, no further effects of age were observed on the cortical potentials examined. Also, neither tone nor speech paradigms showed a significant influence of EHT on the amplitude or latency of either MMN or P300. Conclusions: The application of MMN as an electrophysiological tool to diagnose hidden hearing loss in normal hearing adults has limitations. However, in contrast to MMN responses to tonal stimuli, the present study reveals that MMN amplitude obtained with speech stimuli may indicate early signs of central auditory deficits.<\/jats:p>","DOI":"10.3390\/audiolres15020043","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T04:05:31Z","timestamp":1744776331000},"page":"43","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Can Mismatch Negativity Be Used as an Indicator to Predict Central Auditory Deficits in Individuals with Normal Hearing?"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3964-997X","authenticated-orcid":false,"given":"Lichun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, \u2018Otto K\u00f6rner\u2019, Rostock University Medical Center, Doberaner Stra\u00dfe 137\u2013139, D-18507 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Mi\u00dfler","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, \u2018Otto K\u00f6rner\u2019, Rostock University Medical Center, Doberaner Stra\u00dfe 137\u2013139, D-18507 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karsten","family":"Ehrt","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, \u2018Otto K\u00f6rner\u2019, Rostock University Medical Center, Doberaner Stra\u00dfe 137\u2013139, D-18507 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilma","family":"Gro\u00dfmann","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, \u2018Otto K\u00f6rner\u2019, Rostock University Medical Center, Doberaner Stra\u00dfe 137\u2013139, D-18507 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Mlynski","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, \u2018Otto K\u00f6rner\u2019, Rostock University Medical Center, Doberaner Stra\u00dfe 137\u2013139, D-18507 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian Herrmann","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, \u2018Otto K\u00f6rner\u2019, Rostock University Medical Center, Doberaner Stra\u00dfe 137\u2013139, D-18507 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1001\/archinte.168.14.1522","article-title":"Prevalence of hearing loss and differences by demographic characteristics among US adultsdata from the national health and nutrition examination survey, 1999\u20132004","volume":"168","author":"Agrawal","year":"2008","journal-title":"Arch. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.heares.2013.01.021","article-title":"Current concepts in age-related hearing loss: Epidemiology and mechanistic pathways","volume":"303","author":"Yamasoba","year":"2013","journal-title":"Hear. Res."},{"key":"ref_3","unstructured":"(2018). Addressing the Rising Prevalence of Hearing Loss, World Health Organization."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wang, J., and Puel, J.-L. (2020). Presbycusis: An update on cochlear mechanisms and therapies. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010218"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/S0140-6736(13)61613-X","article-title":"Auditory and non-auditory effects of noise on health","volume":"383","author":"Basner","year":"2014","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.heares.2017.01.003","article-title":"Cochlear synaptopathy in acquired sensorineural hearing loss: Manifestations and mechanisms","volume":"349","author":"Liberman","year":"2017","journal-title":"Hear. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/dneu.22538","article-title":"Myelin development, plasticity, and pathology in the auditory system","volume":"78","author":"Long","year":"2018","journal-title":"Dev. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.heares.2018.02.001","article-title":"Persistent hair cell malfunction contributes to hidden hearing loss","volume":"361","author":"Mulders","year":"2018","journal-title":"Hear. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13452","DOI":"10.1523\/JNEUROSCI.2156-11.2011","article-title":"Tinnitus with a normal audiogram: Physiological evidence for hidden hearing loss and computational model","volume":"31","author":"Schaette","year":"2011","journal-title":"J. Neurosci. Off. J. Soc. Nurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13686","DOI":"10.1523\/JNEUROSCI.1783-13.2013","article-title":"Age-related cochlear synaptopathy: An early-onset contributor to auditory functional decline","volume":"33","author":"Sergeyenko","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1097\/MAO.0b013e3182814d4a","article-title":"Review of hair cell synapse defects in sensorineural hearing impairment","volume":"34","author":"Moser","year":"2013","journal-title":"Otol. Neurotol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14077","DOI":"10.1523\/JNEUROSCI.2845-09.2009","article-title":"Adding insult to injury: Cochlear nerve degeneration after \u201ctemporary\u201d noise-induced hearing loss","volume":"29","author":"Kujawa","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.heares.2015.02.009","article-title":"Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss","volume":"330 Pt B","author":"Kujawa","year":"2015","journal-title":"Hear. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s10162-015-0539-3","article-title":"Towards a diagnosis of cochlear neuropathy with envelope following responses","volume":"16","author":"Shaheen","year":"2015","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.heares.2019.02.016","article-title":"The search for noise-induced cochlear synaptopathy in humans: Mission impossible?","volume":"377","author":"Bramhall","year":"2019","journal-title":"Hear. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Liberman, M.C., Epstein, M.J., Cleveland, S.S., Wang, H., and Maison, S.F. (2016). Toward a differential diagnosis of hidden hearing loss in humans. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162726"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4440","DOI":"10.1121\/10.0007484","article-title":"Use of the auditory brainstem response for assessment of cochlear synaptopathy in humans","volume":"150","author":"Bramhall","year":"2021","journal-title":"J. Acoust. Soc. Am."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4735","DOI":"10.1007\/s00405-024-08699-6","article-title":"The curvature quantification of wave I in auditory brainstem responses detects cochlear synaptopathy in human beings","volume":"281","author":"Schmidt","year":"2024","journal-title":"Eur. Arch. Otorhnilaryngol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1055\/s-0038-1641743","article-title":"Effectiveness of auditory measures for detecting hidden hearing loss and\/or cochlear synaptopathy: A systematic review","volume":"39","author":"James","year":"2018","journal-title":"Semin. Hear."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1152\/jn.00006.2019","article-title":"Hair cell and Neural contributions to the cochlear summating potential","volume":"121","author":"Pappa","year":"2019","journal-title":"J. Neurophysiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/coa.14235","article-title":"Cochlear synaptopathy evaluation with Electrocochleography in patients with hearing difficulty in noise despite normal hearing levels","volume":"50","author":"Atalay","year":"2025","journal-title":"Clin. Otolaryngol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Haggerty, R.A., Hutson, K.A., Riggs, W.J., Brown, K.D., Pillsbury, H.C., Adunka, O.F., Buchman, C.A., and Fitzpatrick, D.C. (2023). Assessment of cochlear synaptopathy by electrocochleography to low frequencies in a preclinical model and human subjects. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1104574"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5542","DOI":"10.1523\/JNEUROSCI.5027-12.2013","article-title":"Efferent feedback minimizes cochlear neuropathy from moderate noise exposure","volume":"33","author":"Maison","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4599","DOI":"10.1523\/JNEUROSCI.4923-13.2014","article-title":"Efferent feedback slows cochlear aging","volume":"34","author":"Liberman","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.neuron.2015.12.041","article-title":"Central gain restores auditory processing following near-complete cochlear denervation","volume":"89","author":"Chambers","year":"2016","journal-title":"Neuron"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1152\/jn.00226.2010","article-title":"Tinnitus, diminished sound-level tolerance, and elevated auditory activity in humans with clinically normal hearing sensitivity","volume":"104","author":"Gu","year":"2010","journal-title":"J. Neurophysiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.brainres.2012.02.008","article-title":"Noise exposure enhances auditory cortex responses related to hyperacusis behavior","volume":"1485","author":"Sun","year":"2012","journal-title":"Brain Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"658741","DOI":"10.1155\/2014\/658741","article-title":"Salicylate-induced auditory perceptual disorders and plastic changes in nonclassical auditory centers in rats","volume":"2014","author":"Chen","year":"2014","journal-title":"Neural. Plast."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.neubiorev.2010.11.003","article-title":"An integrative model of tinnitus based on a central gain controlling neural sensitivity","volume":"35","year":"2011","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Auerbach, B.D., Rodrigues, P.V., and Salvi, R.J. (2014). Central gain control in tinnitus and hyperacusis. Front. Neurol., 5.","DOI":"10.3389\/fneur.2014.00206"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/0001-6918(78)90006-9","article-title":"Early selective-attention effect on evoked potential reinterpreted","volume":"42","author":"Gaillard","year":"1978","journal-title":"Acta Psychol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1097\/00003446-199502000-00002","article-title":"The mismatch negativity: A powerful tool for cognitive neuroscience","volume":"16","year":"1995","journal-title":"Ear Hear."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.heares.2017.07.007","article-title":"The MMN as a viable and objective marker of auditory development in CI users","volume":"353","author":"Petersen","year":"2017","journal-title":"Hear. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1159\/000077265","article-title":"Mismatch negativity brain response as an index of speech perception recovery in cochlear-implant recipients","volume":"9","author":"Lonka","year":"2004","journal-title":"Audiol. Neurotol."},{"key":"ref_35","unstructured":"British Society of Audiology (2025, February 02). Recommended Procedure: Pure Tone Air and Bone Conduction Threshold Audiometry with and Without Masking and Determination of Uncomfortable Loudness Levels. 2004. Available online: https:\/\/www.thebsa.org.uk\/."},{"key":"ref_36","first-page":"62","article-title":"Single-sweep-based methods to improve the quality of auditory brain stem responses Part II: Averaging methods","volume":"40","author":"Riedel","year":"2001","journal-title":"Z. Audiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.clinph.2013.09.035","article-title":"An objective auditory measure to assess speech recognition in adult cochlear implant users","volume":"125","author":"Turgeon","year":"2014","journal-title":"Clin. Neurophysiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1469-8986.1987.tb00311.x","article-title":"The N1 Wave of the human electric and magnetic response to sound: A review and an analysis of the component structure","volume":"24","author":"Picton","year":"1987","journal-title":"Psychophysiology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2331216519900595","DOI":"10.1177\/2331216519900595","article-title":"Neural representation of loudness: Cortical evoked potentials in an induced loudness reduction experiment","volume":"24","author":"Schmidt","year":"2020","journal-title":"Trends Hear."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1152\/jn.00547.2012","article-title":"Mechanisms of adaption in human auditory cortex","volume":"110","author":"Lanting","year":"2013","journal-title":"J. Neurophysiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1016\/j.clinph.2007.04.026","article-title":"The mismatch negativity (MMN) in basic research of central audiotry processing: A review","volume":"118","author":"Paavilainen","year":"2007","journal-title":"Clin. Neurophyiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tao, D., Zhang, Y., Liu, H., Zhang, W., Xu, M., Galvin, J.J., Zhang, D., and Liu, J. (2022). The P300 auditory event-related potential may predict segregation of competing speech by bimodal cochlear implant listeners. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.888596"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1016\/j.clinph.2007.04.019","article-title":"Updating P300: An integrative theory of P3a and P3b","volume":"118","author":"Polich","year":"2007","journal-title":"Clin. Neurophysiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/S1388-2457(99)00108-X","article-title":"Test\u2013retest reliability of mismatch negativity for duration, frequency and intensity changes","volume":"110","author":"Tervaniemi","year":"1999","journal-title":"Clin. Neurophysiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000441693","article-title":"The effect of aging and the high-frequency auditory threshold on speech-evoked mismatch negativity in a nosiy background","volume":"21","author":"Chen","year":"2016","journal-title":"Audiol. Neurootol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chen, J., Zhao, Y., Zou, T., Wen, X., Zhou, X., Yu, Y., Liu, Z., and Li, M. (2022). Sensorineural hearing loss affects functional connectivity of auditory cortex, parahipocampal gyrus and inferior prefrontal gyrus in tinnitus patients. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.816712"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6007","DOI":"10.1523\/JNEUROSCI.0396-20.2020","article-title":"Tinnitus does not interfere with auditory and speech perception","volume":"40","author":"Zeng","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Berthommier, F., Girin, L., and Boe, L.J. (2012, January 9\u201313). A simple hybrid acoustic\/morphologically constrained technique for the synthesis of stop consonants in various vocalic contexts. Proceedings of the Interspeech 2012\u201413th Annual Conference of the International Speech Communication Association, Portland, OR, USA.","DOI":"10.21437\/Interspeech.2012-658"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/0013-4694(93)90185-X","article-title":"Mismatch negativity area and age-related auditory memory","volume":"87","author":"Pekkonen","year":"1993","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1080\/03610739608254005","article-title":"Aging effects on auditory processing: An event-related potential study","volume":"22","author":"Pekkonen","year":"1996","journal-title":"Exp. Aging Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.neurobiolaging.2005.03.012","article-title":"Auditory sensory memory and the aging brain: A mismatch negativity study","volume":"27","author":"Cooper","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.cogbrainres.2005.09.014","article-title":"Age-related change in neural processing of time-dependent stimulus features","volume":"25","author":"Kisley","year":"2005","journal-title":"Cogn. Brain Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"625.e21","DOI":"10.1016\/j.neurobiolaging.2011.03.021","article-title":"Sensory memory during physiological aging indexed by mismatch negativity (MMN)","volume":"33","author":"Ruzzoli","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.clinph.2011.09.020","article-title":"The mismatch negativity (MMN)\u2014A unique window to disturbed central auditory processing in aging and different clinical conditions","volume":"123","author":"Kujala","year":"2012","journal-title":"Clin. Neurophysiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/369517a0","article-title":"Cocktail party effect made tolerable","volume":"369","author":"Maddox","year":"1994","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1515\/JBCPP.2000.11.3.215","article-title":"The varieties of auditory neuropathy","volume":"11","author":"Starr","year":"2000","journal-title":"J. Basic Clin. Physiol. Pharmacol."}],"container-title":["Audiology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-4349\/15\/2\/43\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:15:21Z","timestamp":1760030121000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-4349\/15\/2\/43"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,16]]},"references-count":56,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["audiolres15020043"],"URL":"https:\/\/doi.org\/10.3390\/audiolres15020043","relation":{},"ISSN":["2039-4349"],"issn-type":[{"value":"2039-4349","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,16]]}}}