Auditory Fibers Research Articles

An Open-Source Deep Learning-Based GUI Toolbox For Automated Auditory Brainstem Response Analyses (ABRA).

In this paper, we introduce a new, open-source software developed in Python for analyzing Auditory Brainstem Response (ABR) waveforms. ABRs are a far-field recording of synchronous neural activity generated by the auditory fibers in the ear in response to sound, and used to study acoustic neural information traveling along the ascending auditory pathway. Common ABR data analysis practices are subject to human interpretation and are labor-intensive, requiring manual annotations and visual estimation of hearing thresholds. The proposed new Auditory Brainstem Response Analyzer (ABRA) software is designed to facilitate the analysis of ABRs by supporting batch data import/export, waveform visualization, and statistical analysis. Techniques implemented in this software include algorithmic peak finding, threshold estimation, latency estimation, time warping for curve alignment, and 3D plotting of ABR waveforms over stimulus frequencies and decibels. The excellent performance on a large dataset of ABR collected from three labs in the field of hearing research that use different experimental recording settings illustrates the efficacy, flexibility, and wide utility of ABRA.

Dysfunction of specific auditory fibers impacts cortical oscillations, driving an autism phenotype despite near-normal hearing.

Autism spectrum disorder is discussed in the context of altered neural oscillations and imbalanced cortical excitation-inhibition of cortical origin. We studied here whether developmental changes in peripheral auditory processing, while preserving basic hearing function, lead to altered cortical oscillations. Local field potentials (LFPs) were recorded from auditory, visual, and prefrontal cortices and the hippocampus of BdnfPax2 KO mice. These mice develop an autism-like behavioral phenotype through deletion of BDNF in Pax2+ interneuron precursors, affecting lower brainstem functions, but not frontal brain regions directly. Evoked LFP responses to behaviorally relevant auditory stimuli were weaker in the auditory cortex of BdnfPax2 KOs, connected to maturation deficits of high-spontaneous rate auditory nerve fibers. This was correlated with enhanced spontaneous and induced LFP power, excitation-inhibition imbalance, and dendritic spine immaturity, mirroring autistic phenotypes. Thus, impairments in peripheral high-spontaneous rate fibers alter spike synchrony and subsequently cortical processing relevant for normal communication and behavior.

The sound and musical preferences of tympanic chord

The tympanic chord is a part of the 7th cranial nerve (facial nerve), from which it branches off, runs through the middle ear and then joins the lingual nerve, a part of the 5th cranial nerve (mandibular nerve/trigeminal nerve). Despite its course through the ear, the tympanic chord does not carry auditory fibers, but rather sensory and parasympathetic fibers to the front part of the tongue and to the salivary glands.The cranial nerves V and VII have a common phylogenetic origin, establishing a close relationship between auditory and gustative sense.In German language "Geschmack" means both gustative sense and the preference for different ways of thinking or styles in music, art or fashion. "Musikgeschmack" is the preference for special music styles or composers. "Musikgeschmack" therefore forms an interface between the anatomy of the tympanic chord and music preferences.The effect of parallel processing of music and taste is used, for example, in music therapy or as part of marketing strategies. But it could also be used to treat Covid-19 patients who suffer from a loss of sense of smell and taste. However, there are still no studies on this specific question.

Neurosensory development of the four brainstem-projecting sensory systems and their integration in the telencephalon.

Somatosensory, taste, vestibular, and auditory information is first processed in the brainstem. From the brainstem, the respective information is relayed to specific regions within the cortex, where these inputs are further processed and integrated with other sensory systems to provide a comprehensive sensory experience. We provide the organization, genetics, and various neuronal connections of four sensory systems: trigeminal, taste, vestibular, and auditory systems. The development of trigeminal fibers is comparable to many sensory systems, for they project mostly contralaterally from the brainstem or spinal cord to the telencephalon. Taste bud information is primarily projected ipsilaterally through the thalamus to reach the insula. The vestibular fibers develop bilateral connections that eventually reach multiple areas of the cortex to provide a complex map. The auditory fibers project in a tonotopic contour to the auditory cortex. The spatial and tonotopic organization of trigeminal and auditory neuron projections are distinct from the taste and vestibular systems. The individual sensory projections within the cortex provide multi-sensory integration in the telencephalon that depends on context-dependent tertiary connections to integrate other cortical sensory systems across the four modalities.

Electrocochleography in Auditory Neuropathy Related to Mutations in the OTOF or OPA1 Gene.

Auditory Neuropathy (AN) is characterized by disruption of temporal coding of acoustic signals in auditory nerve fibers resulting in alterations of auditory perceptions. Mutations in several genes have been associated to the most forms of AN. Underlying mechanisms include both pre-synaptic and post-synaptic damage involving inner hair cell (IHC) depolarization, neurotransmitter release, spike initiation in auditory nerve terminals, loss of auditory fibers and impaired conduction. In contrast, outer hair cell (OHC) activities (otoacoustic emissions [OAEs] and cochlear microphonic [CM]) are normal. Disordered synchrony of auditory nerve activity has been suggested as the basis of both the alterations of auditory brainstem responses (ABRs) and reduction of speech perception. We will review how electrocochleography (ECochG) recordings provide detailed information to help objectively define the sites of auditory neural dysfunction and their effect on receptor summating potential (SP) and neural compound action potential (CAP), the latter reflecting disorders of ribbon synapses and auditory nerve fibers.

Cochlear Synaptopathy due to Mutations in OTOF Gene May Result in Stable Mild Hearing Loss and Severe Impairment of Speech Perception.

Congenital profound hearing loss with preserved cochlear outer hair cell activity (otoacoustic emissions and cochlear microphonic) is the most common phenotype associated with mutations in the OTOF gene. The aim of this study was to investigate the pathophysiological mechanisms behind the auditory dysfunction in five patients (2 adults and 3 children) carrying biallelic mutations in OTOF, who showed an uncommon phenotype of mild hearing impairment associated with severe difficulties in speech perception and delay of language development. Patients underwent audiometric assessment with pure-tone and speech perception evaluation, and otoacoustic emissions and auditory brainstem response recording. Cochlear potentials were recorded in all subjects through transtympanic electrocochleography in response to clicks delivered in the free field from 120 to 60 dB peak equivalent SPL and were compared to recordings obtained from 20 normally hearing controls and from eight children with profound deafness due to mutations in the OTOF gene. Three patients out of five underwent unilateral cochlear implantation. Speech perception measures and electrically evoked auditory nerve potentials were obtained within 1 year of cochlear implant use. Pathogenic mutations in the two alleles of OTOF were found in all five patients, and five novel mutations were identified. Hearing thresholds indicated mild hearing loss in four patients and moderate hearing loss in one. Distortion product otoacoustic emissions were recorded in all subjects, whereas auditory brainstem responses were absent in all but two patients, who showed a delayed wave V in one ear. In electrocochleography recordings, cochlear microphonics and summating potentials showed normal latency and peak amplitude, consistently with preservation of both outer and inner hair cell activity. In contrast, the neural compound action potential recorded in normally hearing controls was replaced by a prolonged, low-amplitude negative response. No differences in cochlear potentials were found between OTOF subjects showing mild or profound hearing loss. Electrical stimulation through the cochlear implant improved speech perception and restored synchronized auditory nerve responses in all cochlear implant recipients. These findings indicate that disordered synchrony in auditory fiber activity underlies the impairment of speech perception in patients carrying biallelic mutations in OTOF gene who show a stable phenotype of mild hearing loss. Abnormal nerve synchrony with preservation of hearing sensitivity is consistent with selective impairment of vesicle replenishment at the ribbon synapses with relative preservation of synaptic exocytosis. Cochlear implants are effective in restoring speech perception and synchronous activation of the auditory pathway by directly stimulating auditory fibers.

Simulated auditory fiber myelination heterogeneity desynchronizes population responses to electrical stimulation limiting inter-aural timing difference representation.

Auditory nerve responses to electrical stimulation exhibit aberrantly synchronous response latencies to low-rate pulse trains, nevertheless, cochlear implant users generally have elevated inter-aural timing difference detection thresholds. These findings present an apparent paradox in which single units are unusually precise but downstream within the auditory pathway access to this precision is lost. Auditory nerves innervating a region of cochlea exhibit natural heterogeneity in their diameter, myelination, and other structural properties; a key question is whether this diversity may contribute to the loss of temporal fidelity. In this work, responses of simulated auditory neuron populations with realistic intrinsic diameter and myelination heterogeneity to low-rate pulse trains were produced. By performing a receiver operating characteristic analysis on response latency distributions, ideal-observer interaural timing difference (ITD) detection limits were produced for each population. Fiber heterogeneity produced dispersion of inter-fiber latencies that produced ITD thresholds like that observed in the best performing cochlear implant users. Incorporation of myelin loss into these populations further increased inter-fiber latency variance and elevated ITD detection limits. These findings suggest that the interaction of applied currents with fibers' specific intrinsic properties may introduce fundamental limits on presentation of fine temporal structure in electrical stimulation.

Facial nerve stimulation in a post-meningitic cochlear implant user: using computational modelling as a tool to probe mechanisms and progression of complications on a case-by-case basis

Facial nerve stimulation (FNS) is a side-effect of cochlear implantation that can result in severe discomfort for the user and essentially limits the optimal use of the implant. Three-dimensional cochlear implant modelling research has led to the progression from generic models to user-specific models with one of the intentions to develop model-based diagnostic tools. The objective of this study is to investigate the mechanisms that underlie the manifestation of FNS in the post-meningitic cochleae of a specific CI user through computational modelling. Bilateral models were created using a method previously developed for the construction of a three-dimensional user-specific volume conduction model of the cochlea and was expanded to include the facial nerve geometry. Reduced temporal bone density based on bone densitometry, cochlear duct ossification and degenerate auditory neural fibres were incorporated into a comprehensive FNS model. Auditory and facial nerve thresholds were predicted with the models showing good correspondence to perceptual thresholds and the user's FNS experience. Ossified cochlear ducts appear to aggravate the increase in thresholds caused by the otic capsule's decreased resistivity. This translational case study demonstrates the application of computational modelling as a clinical instrument in the assessment and management of complications with cochlear implantation.

The Neural Bases of Tinnitus: Lessons from Deafness and Cochlear Implants.

Subjective tinnitus is the conscious perception of sound in the absence of any acoustic source. The literature suggests various tinnitus mechanisms, most of which invoke changes in spontaneous firing rates of central auditory neurons resulting from modification of neural gain. Here, we present an alternative model based on evidence that tinnitus is: (1) rare in people who are congenitally deaf, (2) common in people with acquired deafness, and (3) potentially suppressed by active cochlear implants used for hearing restoration. We propose that tinnitus can only develop after fast auditory fiber activity has stimulated the synapse formation between fast-spiking parvalbumin positive (PV+) interneurons and projecting neurons in the ascending auditory path and coactivated frontostriatal networks after hearing onset. Thereafter, fast auditory fiber activity promotes feedforward and feedback inhibition mediated by PV+ interneuron activity in auditory-specific circuits. This inhibitory network enables enhanced stimulus resolution, attention-driven contrast improvement, and augmentation of auditory responses in central auditory pathways (neural gain) after damage of slow auditory fibers. When fast auditory fiber activity is lost, tonic PV+ interneuron activity is diminished, resulting in the prolonged response latencies, sudden hyperexcitability, enhanced cortical synchrony, elevated spontaneous γ oscillations, and impaired attention/stress-control that have been described in previous tinnitus models. Moreover, because fast processing is gained through sensory experience, tinnitus would not exist in congenital deafness. Electrical cochlear stimulation may have the potential to reestablish tonic inhibitory networks and thus suppress tinnitus. The proposed framework unites many ideas of tinnitus pathophysiology and may catalyze cooperative efforts to develop tinnitus therapies.

White Matter Microstructural Abnormalities in the Broca's-Wernicke's-Putamen "Hoffman Hallucination Circuit" and Auditory Transcallosal Fibers in First-Episode Psychosis With Auditory Hallucinations.

Functional connectivity abnormalities between Broca's and Wernicke's areas and the putamen revealed by functional magnetic resonance imaging (fMRI) are related to auditory hallucinations (AH). In long-term schizophrenia, reduced white matter structural integrity revealed by diffusion imaging in left arcuate fasciculus (connecting Broca's and Wernicke's areas) is likely related to AH. The structural integrity of connections with putamen and their relation to AH are unknown. Little is known about this relationship in first-episode psychosis (FEP), although auditory transcallosal connections were reported to play a role. White matter in the Broca's-Wernicke's-putamen language-related circuit and auditory transcallosal fibers was examined to investigate associations with AH in FEP. White matter connectivity was measured in 40 FEP and 32 matched HC using generalized fractional anisotropy (gFA) derived from diffusion spectrum imaging (DSI). FEP and HC did not differ in gFA in any fiber bundle. In FEP, AH severity was significantly inversely related to gFA in auditory transcallosal fibers and left arcuate fasciculus. Although the right hemisphere arcuate fasciculus-AH association did not attain significance, the left and right arcuate fasciculus associations were not significantly different. Despite overall normal gFA in FEP, AH severity was significantly related to gFA in transcallosal auditory fibers and the left hemisphere connection between Broca's and Wernicke's areas. Other bilateral tracts' gFA were weakly associated with AH. At the first psychotic episode, AH are more robustly associated with left hemisphere arcuate fasciculus and interhemispheric auditory fibers microstructural deficits, likely reflecting mistiming of information flow between language-related cortical centers.

Finite element analysis and three-dimensional reconstruction of tonotopically aligned human auditory fiber pathways: A computational environment for modeling electrical stimulation by a cochlear implant based on micro-CT

The application of cochlear implants can be studied with computational models. The electrical potential distribution induced by an implanted device is evaluated with a volume conductor model, which is used as input for neuron models to simulate the reaction of cochlear neurons to micro-stimulation. In order to reliably predict the complex excitation profiles it is vital to consider an accurate representation of the human cochlea geometry including detailed three-dimensional pathways of auditory neurons reaching from the organ of Corti through the cochlea-volume. In this study, high-resolution micro-CT imaging (Δx = Δy = Δz = 3 μm) was used to reconstruct the pathways of 30 tonotopically organized nerve fiber bundles, distributed over eight octaves (11500–40 Hz). Results of the computational framework predict: (i) the peripheral process is most sensitive to cathodic stimulation (CAT), (ii) in many cases CAT elicits spikes in the peripheral terminal at threshold but with larger stimuli there is a second spike initiation site within the peripheral process, (iii) anodic stimuli (ANO) can excite the central process even at threshold, (iv) the recruitment of fibers by electrodes located in the narrowing middle- and apical turn is complex and impedes focal excitation of low frequency fibers, (v) degenerated cells which lost the peripheral process are more sensitive to CAT when their somata are totally covered with 2 membranes of a glial cell but they become ANO sensitive when the myelin covering is reduced.

Enhancer Locus in ch14q23.1 Modulates Brain Asymmetric Temporal Regions Involved in Language Processing.

Identifying the genes that contribute to the variability in brain regions involved in language processing may shed light on the evolution of brain structures essential to the emergence of language in Homo sapiens. The superior temporal asymmetrical pit (STAP), which is not observed in chimpanzees, represents an ideal phenotype to investigate the genetic variations that support human communication. The left STAP depth was significantly associated with a predicted enhancer annotation located in the 14q23.1 locus, between DACT1 and KIAA0586, in the UK Biobank British discovery sample (N = 16 515). This association was replicated in the IMAGEN cohort (N = 1726) and the UK Biobank non-British validation sample (N = 2161). This genomic region was also associated to a lesser extent with the right STAP depth and the formation of sulcal interruptions, "plis de passage," in the bilateral STAP but not with other structural brain MRI phenotypes, highlighting its notable association with the superior temporal regions. Diffusion MRI emphasized an association with the fractional anisotropy of the left auditory fibers of the corpus callosum and with networks involved in linguistic processing in resting-state functional MRI. Overall, this evidence demonstrates a specific relationship between this locus and the establishment of the superior temporal regions that support human communication.

β-Secretase BACE1 Is Required for Normal Cochlear Function

Cleavage of amyloid precursor protein (APP) by β-secretase BACE1 initiates the production and accumulation of neurotoxic amyloid-β peptides, which is widely considered an essential pathogenic mechanism in Alzheimer's disease (AD). Here, we report that BACE1 is essential for normal auditory function. Compared with wild-type littermates, BACE1-/- mice of either sex exhibit significant hearing deficits, as indicated by increased thresholds and reduced amplitudes in auditory brainstem responses (ABRs) and decreased distortion product otoacoustic emissions (DPOAEs). Immunohistochemistry revealed aberrant synaptic organization in the cochlea and hypomyelination of auditory nerve fibers as predominant neuropathological substrates of hearing loss in BACE1-/- mice. In particular, we found that fibers of spiral ganglion neurons (SGN) close to the organ of Corti are disorganized and abnormally swollen. BACE1 deficiency also engenders organization defects in the postsynaptic compartment of SGN fibers with ectopic overexpression of PSD95 far outside the synaptic region. During postnatal development, auditory fiber myelination in BACE1-/- mice lags behind dramatically and remains incomplete into adulthood. We relate the marked hypomyelination to the impaired processing of Neuregulin-1 when BACE1 is absent. To determine whether the cochlea of adult wild-type mice is susceptible to AD treatment-like suppression of BACE1, we administered the established BACE1 inhibitor NB-360 for 6 weeks. The drug suppressed BACE1 activity in the brain, but did not impair hearing performance and, upon neuropathological examination, did not produce the characteristic cochlear abnormalities of BACE1-/- mice. Together, these data strongly suggest that the hearing loss of BACE1 knock-out mice represents a developmental phenotype.SIGNIFICANCE STATEMENT Given its crucial role in the pathogenesis of Alzheimer's disease (AD), BACE1 is a prime pharmacological target for AD prevention and therapy. However, the safe and long-term administration of BACE1-inhibitors as envisioned in AD requires a comprehensive understanding of the various physiological functions of BACE1. Here, we report that BACE1 is essential for the processing of auditory signals in the inner ear, as BACE1-deficient mice exhibit significant hearing loss. We relate this deficit to impaired myelination and aberrant synapse formation in the cochlea, which manifest during postnatal development. By contrast, prolonged pharmacological suppression of BACE1 activity in adult wild-type mice did not reproduce the hearing deficit or the cochlear abnormalities of BACE1 null mice.

Hearing Dysfunction in a Large Family Affected by Dominant Optic Atrophy (OPA8-Related DOA): A Human Model of Hidden Auditory Neuropathy.

Hidden auditory neuropathy is characterized by reduced performances in challenging auditory tasks with the preservation of hearing thresholds, resulting from diffuse loss of cochlear inner hair cell (IHC) synapses following primary degeneration of unmyelinated terminals of auditory fibers. We report the audiological and electrophysiological findings collected from 10 members (4 males, 6 females) of a large Italian family affected by dominant optic atrophy, associated with the OPA8 locus, who complained of difficulties in understanding speech in the presence of noise. The patients were pooled into two groups, one consisting of 4 young adults (19–50 years) with normal hearing thresholds, and the other made up of 6 patients of an older age (55–72 years) showing mild hearing loss. Speech perception scores were normal in the first group and decreased in the second. Otoacoustic emissions (OAEs) and cochlear microphonics (CMs) recordings were consistent with preservation of outer hair cell (OHC) function in all patients, whereas auditory brainstem responses (ABRs) showed attenuated amplitudes in the first group and severe abnormalities in the second. Middle ear acoustic reflexes had delayed peak latencies in all patients in comparison with normally hearing individuals. Transtympanic electrocochleography (ECochG) recordings in response to 0.1 ms clicks at intensities from 120 to 60 dB peak equivalent SPL showed a reduction in amplitude of both summating potential (SP) and compound action potential (CAP) together with delayed CAP peak latencies and prolonged CAP duration in all patients in comparison with a control group of 20 normally hearing individuals. These findings indicate that underlying the hearing impairment in OPA8 patients is hidden AN resulting from diffuse loss of IHCs synapses. At an early stage the functional alterations only consist of abnormalities of ABR and ECochG potentials with increased latencies of acoustic reflexes, whereas reduction in speech perception scores become apparent with progression of the disease. Central mechanisms increasing the cortical gain are likely to compensate for the reduction of cochlear input.

Biosonar capabilities of large-brained dolphins and small-brained bats: Size does matter

The large encephalized brain of the bottlenose dolphin, with a small corpus callosum, functions to maintain continuous, 24-hour biosonar signal processing. Bats are not faced with the dolphin’s challenge of maintaining constant vigilance, as bats are able to retreat to roosts for safety from predators. Although both bats and dolphins echolocate, dolphins face greater challenges in the aquatic environment. Dolphins must locate prey of a similar density to that of the environment, which itself has a high speed of sound transmission. Bats can readily distinguish between prey from the surrounding air because of a strong impedance mismatch, and the speed of sound is much slower. Perhaps stemming from these challenges, dolphins have developed a highly sophisticated echolocation system in which they are able to emit signals and receive echoes, decide, and respond accordingly at a remarkably rapid speed. Dolphin brains may also be specially equipped for early auditory development in utero. The dolphin body has a close impedance match to water, exposing the fetus to environmental sounds. Furthermore, auditory fibers develop myelin early during gestation. Thus, although dolphins and bats both echolocate, the dolphin’s experience during life in the ocean promoted the development of a large and specialized brain.

Stimulation Strategies for Tinnitus Suppression in a Neuron Model.

Tinnitus is a debilitating perception of sound in the absence of external auditory stimuli. It may have either a central or a peripheral origin in the cochlea. Experimental studies evidenced that an electrical stimulation of peripheral auditory fibers may alleviate symptoms but the underlying mechanisms are still unknown. In this work, a stochastic neuron model is used, that mimics an auditory fiber affected by tinnitus, to check the effects, in terms of firing reduction, of different kinds of electric stimulations, i.e., continuous wave signals and white Gaussian noise. Results show that both white Gaussian noise and continuous waves at tens of kHz induce a neuronal firing reduction; however, for the same amplitude of fluctuations, Gaussian noise is more efficient than continuous waves. When contemporary applied, signal and noise exhibit a cooperative effect in retrieving neuronal firing to physiological values. These results are a proof of concept that a combination of signal and noise could be delivered through cochlear prosthesis for tinnitus suppression.

Sparse Labeling and Neural Tracing in Brain Circuits by STARS Strategy: Revealing Morphological Development of Type II Spiral Ganglion Neurons.

Elucidating axonal and dendritic projection patterns of individual neurons is a key for understanding the cytoarchitecture of neural circuits in the brain. This requires genetic approaches to achieve Golgi-like sparse labeling of desired types of neurons. Here, we explored a novel strategy of stochastic gene activation with regulated sparseness (STARS), in which the stochastic choice between 2 competing Cre-lox recombination events is controlled by varying the lox efficiency and cassette length. In a created STARS transgenic mouse crossed with various Cre driver lines, sparse neuronal labeling with a relatively uniform level of sparseness was achieved across different brain regions and cell types in both central and peripheral nervous systems. Tracing of individual type II peripheral auditory fibers revealed for the first time that they undergo experience-dependent developmental refinement, which is impaired by attenuating external sound input. Our results suggest that STARS strategy can be applied for circuit mapping and sparse gene manipulation.

T236. Reduced Integrity of Transcallosal Auditory Fibers and Auditory Hallucinations in the First Episode Schizophrenia Spectrum

T236. Reduced Integrity of Transcallosal Auditory Fibers and Auditory Hallucinations in the First Episode Schizophrenia Spectrum

The effects of the activation of the inner-hair-cell basolateral K+ channels on auditory nerve responses

The basolateral membrane of the mammalian inner hair cell (IHC) expresses large voltage and Ca2+ gated outward K+ currents. To quantify how the voltage-dependent activation of the K+ channels affects the functionality of the auditory nerve innervating the IHC, this study adopts a model of mechanical-to-neural transduction in which the basolateral K+ conductances of the IHC can be made voltage-dependent or not. The model shows that the voltage-dependent activation of the K+ channels (i) enhances the phase-locking properties of the auditory fiber (AF) responses; (ii) enables the auditory nerve to encode a large dynamic range of sound levels; (iii) enables the AF responses to synchronize precisely with the envelope of amplitude modulated stimuli; and (iv), is responsible for the steep offset responses of the AFs. These results suggest that the basolateral K+ channels play a major role in determining the well-known response properties of the AFs and challenge the classical view that describes the IHC membrane as an electrical low-pass filter. In contrast to previous models of the IHC-AF complex, this study ascribes many of the AF response properties to fairly basic mechanisms in the IHC membrane rather than to complex mechanisms in the synapse.

The glucocorticoid antagonist mifepristone attenuates sound-induced long-term deficits in auditory nerve response and central auditory processing in female rats.

Systemic corticosteroids have been the mainstay of treatment for various hearing disorders for more than 30 yr. Accordingly, numerous studies have described glucocorticoids (GCs) and stressors to be protective in the auditory organ against damage associated with a variety of health conditions, including noise exposure. Conversely, stressors are also predictive risk factors for hearing disorders. How both of these contrasting stress actions are linked has remained elusive. Here, we demonstrate that higher corticosterone levels during acoustic trauma in female rats is highly correlated with a decline of auditory fiber responses in high-frequency cochlear regions, and that hearing thresholds and the outer hair cell functions (distortion products of otoacoustic emissions) are left unaffected. Moreover, when GC receptor (GR) or mineralocorticoid receptor (MR) activation was antagonized by mifepristone or spironolactone, respectively, GR, but not MR, inhibition significantly and permanently attenuated trauma-induced effects on auditory fiber responses, including inner hair cell ribbon loss and related reductions of early and late auditory brainstem responses. These findings strongly imply that higher corticosterone stress levels profoundly impair auditory nerve processing, which may influence central auditory acuity. These changes are likely GR mediated as they are prevented by mifepristone.-Singer, W., Kasini, K., Manthey, M., Eckert, P., Armbruster, P., Vogt, M. A., Jaumann, M., Dotta, M., Yamahara, K., Harasztosi, C., Zimmermann, U., Knipper, M., Rüttiger, L. The glucocorticoid antagonist mifepristone attenuates sound-induced long-term deficits in auditory nerve response and central auditory processing in female rats.