{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T01:04:38Z","timestamp":1786410278804,"version":"build-2736575974"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["764604"],"award-info":[{"award-number":["764604"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Tinnitus is a complex and not yet fully understood phenomenon. Often the treatments provided are effective only for subgroups of sufferers. We are presently not able to predict benefit with the currently available diagnostic tools and analysis methods. Being able to identify and specifically treat sub-categories of tinnitus would help develop and implement more targeted treatments with higher success rate. In this study we use a clustering analysis based on 17 predictors to cluster an audiologically homogeneous group of normal hearing participants, both with and without tinnitus. The predictors have been chosen to be either tinnitus-specific measures or measures that are thought to be connected to cochlear synaptopathy. Our aim was to identify a subgroup of participants with characteristics consistent with the current hypothesized impact of cochlear synaptopathy. Our results show that this approach can separate the listeners into different clusters. But not in all cases could the tinnitus sufferers be separated from the control group. Another challenge is the use of categorical measures which seem to dominate the importance analysis of the factors. The study showed that data-driven clustering of a homogeneous listener group based on a mixed set of experimental outcome measures is a promising tool for tinnitus sub-typing, with the caveat that sample sizes might need to be sufficiently high, and higher than in the present study, to keep a meaningful sample size after clustering.<\/jats:p>","DOI":"10.1371\/journal.pone.0277023","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T18:53:55Z","timestamp":1670957635000},"page":"e0277023","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Categorization of tinnitus listeners with a focus on cochlear synaptopathy"],"prefix":"10.1371","volume":"17","author":[{"given":"Chiara","family":"Casolani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James Michael","family":"Harte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8062-0837","authenticated-orcid":true,"given":"Bastian","family":"Epp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"pone.0277023.ref001","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.heares.2016.05.009","article-title":"A systematic review of the reporting of tinnitus prevalence and severity","volume":"337","author":"A McCormack","year":"2016","journal-title":"Hearing Research"},{"key":"pone.0277023.ref002","unstructured":"Association AT. Understanding the Facts;. Available from: https:\/\/www.ata.org\/understanding-facts."},{"key":"pone.0277023.ref003","doi-asserted-by":"crossref","first-page":"802","DOI":"10.3389\/fnins.2019.00802","article-title":"Why is there no cure for tinnitus?","volume":"13","author":"DJ McFerran","year":"2019","journal-title":"Frontiers in Neuroscience"},{"key":"pone.0277023.ref004","first-page":"285","volume-title":"Tinnitus and Hearing Loss","author":"G Baracca","year":"2011"},{"issue":"1","key":"pone.0277023.ref005","first-page":"120","article-title":"Diagnostic Approach to Tinnitus","volume":"69","author":"RW Crummer","year":"2004","journal-title":"American Family Physician"},{"key":"pone.0277023.ref006","volume-title":"Tinnitus: Facts, Theories, and Treatments","author":"National Research Council (US) Committee on Hearing, Bioacoustics, and Biomechanics","year":"1982"},{"issue":"2","key":"pone.0277023.ref007","first-page":"124","article-title":"Quantitative electroencephalography and tinnitus: A case study","volume":"6","author":"EWJ Weiler","year":"2000","journal-title":"International Tinnitus Journal"},{"issue":"38","key":"pone.0277023.ref008","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":"R Schaette","year":"2011","journal-title":"Journal of Neuroscience"},{"issue":"6","key":"pone.0277023.ref009","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s10162-012-0344-1","article-title":"Brainstem auditory evoked potentials suggest a role for the ventral cochlear nucleus in tinnitus","volume":"13","author":"JW Gu","year":"2012","journal-title":"Jaro\u2014Journal of the Association for Research in Otolaryngology"},{"key":"pone.0277023.ref010","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3389\/fnagi.2017.00237","article-title":"Auditory brainstem responses in tinnitus: A review of who, how, and what?","volume":"9","author":"V Milloy","year":"2017","journal-title":"Frontiers in Aging Neuroscience"},{"key":"pone.0277023.ref011","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.nicl.2018.08.029","article-title":"Reduced sound-evoked and resting-state BOLD fMRI connectivity in tinnitus","volume":"20","author":"B Hofmeier","year":"2018","journal-title":"Neuroimage: Clinical"},{"issue":"10","key":"pone.0277023.ref012","doi-asserted-by":"crossref","first-page":"e110704","DOI":"10.1371\/journal.pone.0110704","article-title":"Unilateral tinnitus: Changes in connectivity and response lateralization measured with fMRI","volume":"9","author":"CP Lanting","year":"2014","journal-title":"Plos One"},{"issue":"4","key":"pone.0277023.ref013","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1159\/000430459","article-title":"Pump up the volume: Could excessive neural gain explain tinnitus and hyperacusis?","volume":"20","author":"H Brotherton","year":"2015","journal-title":"Audiology and Neurotology"},{"issue":"2","key":"pone.0277023.ref014","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10162-015-0550-8","article-title":"Selective Inner Hair Cell Dysfunction in Chinchillas Impairs Hearing-in-Noise in the Absence of Outer Hair Cell Loss","volume":"17","author":"E Lobarinas","year":"2016","journal-title":"JARO\u2014Journal of the Association for Research in Otolaryngology"},{"key":"pone.0277023.ref015","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","author":"SG Kujawa","year":"2015","journal-title":"Hearing Research"},{"issue":"Sp. Iss. SI","key":"pone.0277023.ref016","first-page":"8","article-title":"Primary Neural Degeneration in the Human Cochlea: Evidence for Hidden Hearing Loss in the Aging Ear","volume":"407","author":"PZ Wu","year":"2019","journal-title":"Neuroscience"},{"issue":"6","key":"pone.0277023.ref017","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0363-17.2017","article-title":"Weak Middle-Ear-Muscle Reflex in Humans with Noise-Induced Tinnitus and Normal Hearing May Reflect Cochlear Synaptopathy","volume":"4","author":"M Wojtczak","year":"2017","journal-title":"Eneuro"},{"issue":"Sp. Iss. SI","key":"pone.0277023.ref018","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.neuroscience.2018.12.019","article-title":"Acoustic Middle-Ear-Muscle-Reflex Thresholds in Humans with Normal Audiograms: No Relations to Tinnitus, Speech Perception in Noise, or Noise Exposure","volume":"407","author":"H Guest","year":"2019","journal-title":"Neuroscience"},{"key":"pone.0277023.ref019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/2331216519878539","article-title":"Comparing Tinnitus Tuning Curves and Psychoacoustic Tuning Curves","volume":"23","author":"P Fournier","year":"2019","journal-title":"Trends in Hearing"},{"issue":"9","key":"pone.0277023.ref020","doi-asserted-by":"crossref","first-page":"e0162726","DOI":"10.1371\/journal.pone.0162726","article-title":"Toward a differential diagnosis of hidden hearing loss in humans","volume":"11","author":"MC Liberman","year":"2016","journal-title":"Plos One"},{"issue":"Sp. Iss. SI","key":"pone.0277023.ref021","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.neuroscience.2018.12.038","article-title":"Enhanced Central Neural Gain Compensates Acoustic Trauma-induced Cochlear Impairment, but Unlikely Correlates with Tinnitus and Hyperacusis","volume":"407","author":"D M\u00f6hrle","year":"2019","journal-title":"Neuroscience"},{"key":"pone.0277023.ref022","unstructured":"MATLAB. version 7.10.0 (R2017a). Natick, Massachusetts: The MathWorks Inc.; 2016."},{"issue":"6","key":"pone.0277023.ref023","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1159\/000066156","article-title":"Psychoacoustic characterization of the tinnitus spectrum: Implications for the underlying mechanisms of tinnitus","volume":"7","author":"A Norena","year":"2002","journal-title":"Audiology and Neuro-otology"},{"issue":"4","key":"pone.0277023.ref024","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1121\/1.1502902","article-title":"An adaptive procedure for categorical loudness scaling","volume":"112","author":"T Brand","year":"2002","journal-title":"Journal of the Acoustical Society of America"},{"key":"pone.0277023.ref025","unstructured":"Sanchez Lopez R, Fereczkowski M, Bianchi F, El-Haj-Ali M, Neher T, Dau T, et al. Auditory tests for characterizing individual hearing deficits: The BEAR test battery. 2018;."},{"issue":"1","key":"pone.0277023.ref026","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1097\/AUD.0000000000000804","article-title":"Middle Ear Muscle Reflex and Word Recognition in \u201cnormal-Hearing\u201d Adults: Evidence for Cochlear Synaptopathy?","volume":"41","author":"AM Mepani","year":"2018","journal-title":"Ear and Hearing"},{"issue":"1-2","key":"pone.0277023.ref027","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.heares.2009.09.008","article-title":"Wideband acoustic-reflex test in a test battery to predict middle-ear dysfunction","volume":"263","author":"DH Keefe","year":"2010","journal-title":"Hearing Research"},{"issue":"1","key":"pone.0277023.ref028","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1121\/1.5047436","article-title":"Audiogram estimation using Bayesian active learning","volume":"144","author":"J Schlittenlacher","year":"2018","journal-title":"The Journal of the Acoustical Society of America"},{"key":"pone.0277023.ref029","unstructured":"R Core Team. R: A Language and Environment for Statistical Computing; 2020. Available from: https:\/\/www.R-project.org\/."},{"key":"pone.0277023.ref030","article-title":"Pattern recognition with fuzzy objective function algorithms","author":"JC Bezdek","year":"1981","journal-title":"Plenum"},{"issue":"1","key":"pone.0277023.ref031","first-page":"012097","article-title":"Application of partitioning around medoids cluster for analysis of stunting in 100 priority regencies in Indonesia","volume":"1722","author":"MA Ramdani","year":"2021","journal-title":"Journal of Physics: Conference Series"},{"issue":"4","key":"pone.0277023.ref032","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1016\/j.csda.2007.08.015","article-title":"Empirical characterization of random forest variable importance measures","volume":"52","author":"KJ Archer","year":"2008","journal-title":"Computational Statistics and Data Analysis"},{"key":"pone.0277023.ref033","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0169-7161(04)24011-1","article-title":"Classification and Regression Trees, Bagging, and Boosting","volume":"24","author":"CD Sutton","year":"2005","journal-title":"Handbook of Statistics"},{"key":"pone.0277023.ref034","doi-asserted-by":"crossref","unstructured":"Frazier PI. A Tutorial on Bayesian Optimization. 2018;.","DOI":"10.1287\/educ.2018.0188"},{"issue":"4","key":"pone.0277023.ref035","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1037\/1040-3590.6.4.284","article-title":"Guidelines, criteria, and rules of thumb for evaluating normed and standardized assessment instruments in psychology","volume":"6","author":"DV Cicchetti","year":"1994","journal-title":"Psychological Assessment"},{"issue":"2","key":"pone.0277023.ref036","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jcm.2016.02.012","article-title":"A Guideline of Selecting and Reporting Intraclass Correlation Coefficients for Reliability Research","volume":"15","author":"TK Koo","year":"2016","journal-title":"Journal of Chiropractic Medicine"},{"issue":"3","key":"pone.0277023.ref037","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1159\/000276126","article-title":"Clinical and audiological characteristics of tonal and noise tinnitus","volume":"52","author":"A Kodama","year":"1990","journal-title":"Orl-journal for Oto-rhino-laryngology and Its Related Specialties"},{"key":"pone.0277023.ref038","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.heares.2018.03.012","article-title":"Effects of cochlear synaptopathy on middle-ear muscle reflexes in unanesthetized mice","volume":"363","author":"MD Valero","year":"2018","journal-title":"Hearing Research"},{"issue":"1","key":"pone.0277023.ref039","doi-asserted-by":"crossref","first-page":"113","DOI":"10.9758\/cpn.2019.17.1.113","article-title":"Gender differences affecting psychiatric distress and tinnitus severity","volume":"17","author":"TS Han","year":"2019","journal-title":"Clinical Psychopharmacology and Neuroscience"},{"issue":"July","key":"pone.0277023.ref040","first-page":"1","article-title":"Gender Comparison of Psychological Comorbidities in Tinnitus Patients\u2014Results of a Cross-Sectional Study","volume":"14","author":"A Fioretti","year":"2020","journal-title":"Frontiers in Neuroscience"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0277023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T18:54:33Z","timestamp":1670957673000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0277023"}},"subtitle":[],"editor":[{"given":"Susan E","family":"Shore","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,12,13]]},"references-count":40,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0277023","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,13]]}}}