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Neuroscience. 2019 May 21;407:146-169. doi: 10.1016/j.neuroscience.2018.12.038. Epub 2018 Dec 29.

Enhanced Central Neural Gain Compensates Acoustic Trauma-induced Cochlear Impairment, but Unlikely Correlates with Tinnitus and Hyperacusis.

Author information

1
University of Tübingen, Department of Otolaryngology, Head & Neck Surgery, Tübingen Hearing Research Centre (THRC), Molecular Physiology of Hearing, Elfriede-Aulhorn-Straße 5, 72076 Tübingen, Germany. Electronic address: dorit.moehrle@googlemail.com.
2
University of Tübingen, Department of Otolaryngology, Head & Neck Surgery, Tübingen Hearing Research Centre (THRC), Molecular Physiology of Hearing, Elfriede-Aulhorn-Straße 5, 72076 Tübingen, Germany. Electronic address: benedikt.hofmeier@uni-tuebingen.de.
3
University of Tübingen, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Röntgenweg 13, 72076 Tübingen, Germany. Electronic address: mario.amend@med.uni-tuebingen.de.
4
University of Tübingen, Department of Otolaryngology, Head & Neck Surgery, Tübingen Hearing Research Centre (THRC), Molecular Physiology of Hearing, Elfriede-Aulhorn-Straße 5, 72076 Tübingen, Germany. Electronic address: Stephan.wolpert@med.uni-tuebingen.de.
5
University of Tübingen, Department of Otolaryngology, Head & Neck Surgery, Tübingen Hearing Research Centre (THRC), Molecular Physiology of Hearing, Elfriede-Aulhorn-Straße 5, 72076 Tübingen, Germany; Shanghai Jiao Tong University, Department of Otolaryngology, Head & Neck Surgery, Shanghai Children's Hospital, Shanghai Luding Road, NO. 355. Putuo District, 200062 Shanghai, China. Electronic address: nikun1008@163.com.
6
University of Tübingen, Department of Otolaryngology, Head & Neck Surgery, Tübingen Hearing Research Centre (THRC), Molecular Physiology of Hearing, Elfriede-Aulhorn-Straße 5, 72076 Tübingen, Germany. Electronic address: didibing1981@aliyun.com.
7
University Hospital Tübingen, Department of Diagnostic and Interventional Neuroradiology, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany. Electronic address: uwe.klose@med.uni-tuebingen.de.
8
University of Tübingen, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Röntgenweg 13, 72076 Tübingen, Germany. Electronic address: bernd.pichler@med.uni-tuebingen.de.
9
University of Tübingen, Department of Otolaryngology, Head & Neck Surgery, Tübingen Hearing Research Centre (THRC), Molecular Physiology of Hearing, Elfriede-Aulhorn-Straße 5, 72076 Tübingen, Germany. Electronic address: marlies.knipper@uni-tuebingen.de.
10
University of Tübingen, Department of Otolaryngology, Head & Neck Surgery, Tübingen Hearing Research Centre (THRC), Molecular Physiology of Hearing, Elfriede-Aulhorn-Straße 5, 72076 Tübingen, Germany. Electronic address: lukas.ruettiger@uni-tuebingen.de.

Abstract

For successful future therapeutic strategies for tinnitus and hyperacusis, a subcategorization of both conditions on the basis of differentiated neural correlates would be of invaluable advantage. In the present study, we used our refined operant conditioning animal model to divide equally noise-exposed rats into groups with either tinnitus or hyperacusis, with neither condition, or with both conditions co-occurring simultaneously. Using click stimulus and noise burst-evoked Auditory Brainstem Responses (ABR) and Distortion Product Otoacoustic Emissions, no hearing threshold difference was observed between any of the groups. However, animals with neither tinnitus nor hyperacusis responded to noise trauma with shortened ABR wave I and IV latencies and elevated central neuronal gain (increased ABR wave IV/I amplitude ratio), which was previously assumed in most of the literature to be a neural correlate for tinnitus. In contrast, animals with tinnitus had reduced neural response gain and delayed ABR wave I and IV latencies, while animals with hyperacusis showed none of these changes. Preliminary studies, aimed at establishing comparable non-invasive objective tools for identifying tinnitus in humans and animals, confirmed reduced central gain and delayed response latency in human and animals. Moreover, the first ever resting state functional Magnetic Resonance Imaging (rs-fMRI) analyses comparing humans and rats with and without tinnitus showed reduced rs-fMRI activities in the auditory cortex in both patients and animals with tinnitus. These findings encourage further efforts to establish non-invasive diagnostic tools that can be used in humans and animals alike and give hope for differentiated classification of tinnitus and hyperacusis.

KEYWORDS:

central compensation; hidden hearing loss; hyperacusis; inner hair cell synaptopathy; neural gain; tinnitus

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