Hearing Dysfunction Research Articles

Objective Voice Analysis in Partial Deafness: Comparison of Multi-Dimensional Voice Program (MDVP) and VOXplot Results

Acoustic analysis of voice enables objective assessment of voice to diagnose changes in voice characteristics, and track the progress of therapy. In contrast to subjective assessment, objective measurements provide mathematical results referring to specific parameters and can be analyzed statistically. Changes in the voice of patients with partial deafness (PD) were not widely described in the literature, and recent studies referred to the voice parameters measured in this group of patients only using the multi-dimensional voice program (MDVP) by Kay Pentax. This paper describes the results of acoustic analysis of voice in patients with PD using VOXplot, and compares the results with those achieved with MDVP. Background/Objectives: The purpose of this study was a VOXplot objective analysis of voice in individuals with PD and to assess consistency with results obtained using MDVP and with perceptual assessment. Methods: Voice samples from 22 post-lingual PD individuals were recorded. They included continuous speech (cs) and sustained vowels (sv). The control group consisted of 22 healthy individuals with no history of voice or hearing dysfunction. The samples were analyzed with MDVP followed by VOXplot version 2.0.0 Beta. Statistical analysis was performed using a t-test paired with two samples for means. All individuals were also subjected to a perceptual voice assessment using the GRBAS by Hirano. Results: Differences were observed in 13 VOXplot parameters measured in voice samples of adults with PD compared with those in the control group. Both multiparametric indices, AVQI and ABI, showed a statistical increase. When it comes to MDVP parameters correlating with breathiness, all of them (shim dB, APQ, NHR, SPI, and NSH) increased in patients with partial deafness, reflecting a breathy voice. Only one increase in the SPI was not statistically significant. Seven MDVP parameters correlating with hoarseness were elevated, and five (Jitt%, vF0, Shim dB, APQ, and NHR) showed a statistically significant increase. Correlations were found of VOXplot and MDVP parameters with perceptual voice assessment. Conclusions: Both programs for objective assessment showed voice abnormalities in patients with PD compared with the control groups. There was a poor to moderate level of consistency in the results achieved using both systems. Correlations were also found with GRBAS assessment results.

Otolaryngological manifestations in patients with obstructive sleep apnea and continuous positive airway pressure users: A systematic review.

Sleep disorders have emerged as a significant public health issue, adversely affecting quality of life and precipitating severe complications. The association between obstructive sleep apnea syndrome (OSAS) and otolaryngological manifestations appears to be underrecognized. This study posits that manifestations in the ear, nose and throat (ENT) among patients with OSAS and users of continuous positive airway pressure (CPAP) therapy are relatively common. Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, this systematic review, registered at PROSPERO (No. CRD42023452473), involved a comprehensive search of the MEDLINE databases. We included studies published in English from 1979 to March 2021 that explored the linkages between OSAS, CPAP and otolaryngological manifestations. A total of 29 articles were reviewed, with findings indicating 12 studies on ear dysfunctions, 11 on nose dysfunctions and 6 on pharynx dysfunctions. Reported symptoms included hearing dysfunction, vestibular function disorders, cerebrospinal fluid leak, Eustachian tube (ET) dysfunction, rhinosinusitis, olfaction and taste disorders, dysphagia, dry mouth, and gastroesophageal reflux. The etiology of these ailments varies, yet an understanding of these symptoms can improve the diagnosis to confirm or rule out OSAS. Early identification of ENT symptoms related to OSAS may facilitate prompt diagnosis and mitigate serious complications.

8518 Prevalence of Hearing Dysfunction in Patients with Autoimmune Thyroid Disorders, Thyroid Eye Disease and the General US population: A Claims Database Analysis

Abstract Disclosure: T.J. Smith: Consulting Fee; Self; Amgen Inc, Viridian, Minghui, Lassen, Lundbeck. Other; Self; US patents covering the use of IGF-1 receptor inhibitors in TED which are held by UCLA and the Lundquist Institute. A. Meyers: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. Q. Fu: Stock Owner; Self; Amgen Inc. Other; Self; Amgen Inc, former employee. R.J. Holt: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. K. Zhu: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. Background: Autoimmune thyroid conditions including Graves’ disease (GD) have been associated with hearing impairment.([1]-3) Approximately 90% of patients (pts) with thyroid eye disease (TED) have hyperthyroidism/GD. Teprotumumab, an insulin-like growth factor-I receptor inhibitor, significantly improves TED signs/symptoms and became the first FDA-approved treatment for TED in 2020. Hearing-related adverse events were identified in pivotal trials of teprotumumab in TED.4 This epidemiology study aims to describe the prevalence of hearing loss/ototoxicity via claims data in commercially insured pts with autoimmune thyroid conditions, TED, and those receiving teprotumumab, as well as the general population (gen pop). Methods: Five mutually exclusive cohorts were created using deidentified claims data (Merative MarketScan®): GD pts (index is first GD diagnosis [dx] code), TED pts (index is later of both GD dx or eye symptom codes within 1 yr), teprotumumab pts (index is first claim for teprotumumab), other Thyroid Disorders (TD) pts (index is TD dx), and gen pop pts. Pts with teprotumumab claim were excluded from other cohorts. Eligible pts were ≥18 years (yrs) of age, continuously enrolled for ≥6 months pre and post index, between 1/1/2020-12/21/2021. Demographics (age, sex) were described between the cohorts and the gen pop. Proportions of pts with inpatient and outpatient claims for hearing loss/ototoxicity claims and proportions with hearing loss/ototoxicity claims in the 3 yrs preceding index were calculated. Age-standardized prevalence was presented using gen pop as the reference. Results: Of 21,256,714 eligible pts, 82,629 GD, 4,455 TED, 2,758 teprotumumab, 1,261,250 TD and 4,857,408 gen pop pts were identified. 47% pts in the gen pop cohort were female vs 72.1-75.7% in the other cohorts. Gen pop cohort was younger (mean [SD] age: 53 [15.1] yrs) vs 58.0-61.5 [15.1-15.6] yrs in other cohorts. Age-standardized prevalence of hearing loss/ototoxicity claims on/after index date was 3.3% for GD, 5.2% for TED, 4.3% for teprotumumab, 3.9% for TD, and 3.9% for gen pop pts. Hearing loss/ototoxicity claims were prevalent in the 3 years prior to index among these patients: 30.8% GD, 36.6% TED, 35.4% teprotumumab, 31.5% TD, and 27.3%) gen pop pts had a hearing loss/ototoxicity claim. Conclusions: In this descriptive unadjusted analysis, we observed similar prevalence of hearing loss/ototoxicity claims across thyroid disorders, TED pts, teprotumumab pts, and the gen pop group. Between 27%-37% had claims prior to thyroid diagnosis or receiving teprotumumab. It is expected that future analyses could adjust the rates for potential confounders across cohorts.

Roadmap to a Global Template for Implementation of Ototoxicity Management for Cancer Treatment.

Ototoxicity is among the adverse events related to cancer treatment that can have far-reaching consequences and negative impacts on quality-of-life for cancer patients and survivors of all ages. Ototoxicity management (OtoM) comprises the prevention, diagnosis, monitoring, and treatment, including rehabilitation and therapeutic intervention, of individuals who experience hearing loss, tinnitus, or balance/vestibular difficulties following exposures to ototoxic agents, including platinum chemotherapy (cisplatin, carboplatin) and cranial radiation. Despite the well-established physical, socioeconomic, and psychological consequences of hearing and balance dysfunction, there are no widely adopted standards for clinical management of cancer treatment-related ototoxicity. Consensus recommendations and a roadmap are needed to guide development of effective and feasible OtoM programs, direct research efforts, address the needs of caregivers and patients at all stages of cancer care and survivorship. Here we review current evidence and propose near-term to longer-term goals to advance OtoM in five strategic areas: (1) beneficiary awareness, empowerment, and engagement, (2) workforce enhancement, (3) program development, (4) policy, funding, and sustainability, and (5) research and evaluation. The goal is to identify needs and establish a roadmap to guide worldwide adoption of standardized OtoM for cancer treatment and improved outcomes for patients and survivors.

Patterns of Teprotumumab-Induced Hearing Dysfunction: A Systematic Review.

Hearing loss has been reported after administration of the monoclonal antibody teprotumumab. The purpose of this study was to review available evidence regarding the patterns of teprotumumab-related ototoxicity. PubMed, EMBASE, and Cochrane Library. A systematic review was performed using standardized methodology. Studies were included if they included subjects who were prescribed teprotumumab. Exclusion criteria included non-English articles, abstracts, letters/commentaries, case reports, and reviews. Subjects without both pre- and posttreatment audiometric data were also excluded. Bias was assessed using the Mixed Methods Appraisal Tool. From an initial search of 76 articles, 7 studies reporting on 109 unique patients were included. Four studies were level 4 evidence, 1 study was level 3 evidence, and 2 studies were level 2 evidence. Mean age was 55 ± 14 years with a female predominance (64%). The most commonly reported symptoms were hearing loss (22%), followed by fullness (18%) and tinnitus (14%). In total, 41% of patients with available data met criteria for ototoxicity, all exhibiting shifts in the middle frequencies or higher. Fifteen (14%) patients underwent ultrahigh frequency audiometric testing and 8 (53%, 8/15) demonstrated shifts exclusively in this range. Ototoxicity may occur in patients treated with teprotumumab. Hearing loss occurs primarily in higher frequencies, and routine hearing screening with ultrahigh frequency testing may be warranted. The true incidence of ototoxicity with teprotumumab remains unknown, and more data is needed to elucidate underlying mechanisms and develop strategies to minimize risks.

Assessment of hearing dysfunction in patients with Graves' disease and thyroid eye disease without or with teprotumumab.

Thyroid eye disease (TED) negatively impacts quality of life. TED occurs predominantly in Graves' disease (GD). Teprotumumab improves TED but concern for hearing adverse events (AEs) has emerged. Hearing dysfunction is reported in thyroid autoimmune disease but the background prevalence in GD/TED without teprotumumab remains uncertain. To quantify ear-related diagnostic codes/hearing AEs in GD, TED, and patients receiving teprotumumab by examining medical claims and clinical trials. Deidentified claims for ear/labyrinth-related ICD-10 codes (KOMODO®) were examined in GD patients without TED, and TED patients without/with teprotumumab treatment. Hearing AE incidence/severity was evaluated in teprotumumab clinical trials. Graves' Ophthalmopathy QOL (GO-QOL) scores were compared in teprotumumab TED trial patients without/with hearing AEs. GD (469,720), TED (38,566) and teprotumumab-treated (967) patients were identified in the claims database. Ear-related codes (including those not specific for hearing) occurred in 24% GD, 33% TED, and 32% teprotumumab-treated patients. "Sensorineural hearing loss bilateral" was most frequent: 32,961/469,720 (7%) GD, 4,279/38,566 (11.1%) TED, and 104/967 (10.8%) teprotumumab patients. Pre-teprotumumab use,165 (17.1%) patients had ear-related codes while 98 (10.1%) had new ear-related codes post-treatment.Eight teprotumumab oncology trials revealed 8.1% (51/633) had Ear/Labyrinth Disorders with 2.1% (13) considered study-drug-related and 3.8% (24) hearing impairment/tinnitus-related AEs, with 1.3% (8) considered teprotumumab-related. Similar rates occurred in TED trials.GO-QOL improved in teprotumumab-treated patients without/with hearing AEs. Incidence/severity was consistent across patients with chronic and acute TED. These analyses indicate similar occurrence of hearing claims in patients with GD/TED alone as following teprotumumab treatment. Future analyses of incremental hearing risk from teprotumumab should utilize a priori study designs accounting for background hearing dysfunction in patients with GD/TED.

The effectiveness of curcumin as a safe agent on hearing threshold improvement in patients with chronic kidney disease: a double-blind, placebo-controlled trial

Hearing impairment in patients with chronic kidney disease (CKD), can affect the quality of life. At present, hearing dysfunction does not have an approved pharmacologic therapy. This study aimed to investigate the protective effects and possible mechanisms of curcumin as a therapeutic agent on hearing impairment in patients with chronic kidney disease. We conducted a randomized controlled trial of 40 chronic kidney disease patients not on dialysis with hearing impairment. Participants were randomly divided into two groups. One group received curcumin daily and the other received a placebo for 12 weeks. The interval between III and V waves, latency of wave V, auditory brain stem response (ABR) threshold, speech reception threshold (SRT), and speech discrimination score (SDS) were evaluated and analyzed before and after the intervention. After treatment, in the curcumin group, III–V waves interval and the latency of wave V were significantly reduced (P value < 0.0001), also ABR threshold was demonstrated a significant improvement (P value < 0.0001). In the trial group, the SDS was increased (P = 0.001) and the SRT was attenuated (P < 0.0001). We had either significant deterioration due to the course of the disease or insignificant changes in the placebo group. Daily administration of curcumin, can significantly improve hearing impairment in CKD patients. Accordingly, curcumin should be considered as a therapeutic option for treating hearing impairment in patients with chronic kidney disease.

The Effect of Rheumatoid Arthritis on Middle and Inner Ear Functions.

To investigate the middle and inner ear functions, and efferent auditory systems in patients with rheumatoid arthritis (RA). Thirty-five RA patients and 40 control subjects participated in the study. Pure-tone audiometry, high-frequency audiometry, multifrequency tympanometry, transient evoked otoacoustic emissions, and contralateral suppression tests were administered to all participants. Pure-tone hearing thresholds of RA patients were significantly higher at all frequencies except for 2000 Hz, 14,000 Hz, and 16,000 Hz in the right ear and 16,000 Hz in the left ear (p<0.05). Resonance frequency values of RA patients were statistically significantly lower than those of the control group (p<0.001). Emission amplitudes obtained with contralateral acoustic stimulation were significantly lower at 1400 Hz frequency in both groups than without contralateral acoustic stimulation (p<0.05). While contralateral suppression was observed at all frequencies in the control group, no suppression occurred at 2800 Hz and 4000 Hz in RA patients. The results obtained in this study demonstrated the presence of hearing dysfunction in patients with RA. When a patient is diagnosed with RA, an audiological evaluation should be made, and the patient should be informed about the possibility of audiological involvement.

Long-Term Update of a Phase 3 Randomized Study Comparing Once-a-Week Versus Once-Every-3-Weeks Cisplatin Along With Radiation in Head and Neck Cancer

PurposeIn the weekly-3-weekly (W3W) study, cisplatin at 100 mg/m2 once-every-3-weeks led to superior locoregional control compared to cisplatin 30 mg/m2 once-a-week in combination with radical radiation for locally advanced head and neck squamous cell carcinoma (LAHNSCC). We report the updated analysis of the study. MethodsIn this phase III open label non-inferiority study conducted between 2013 and 2017, 300 patients with LAHNSCC were randomly assigned to receive cisplatin 100 mg/m2 once-in-3-weeks or cisplatin 30 mg/m2 once-a-week, concurrently with radiation. The primary endpoint was locoregional control (LRC). Secondary outcomes were overall survival (OS), progression free survival (PFS) and late adverse events. ResultsThe median follow-up was 6.91 years (95% CI, 6.12-7.36). The updated 2-year and 5-year LRC rates for the once-a-week cisplatin arm were 58.75% (95% CI, 51.08- 67.58) and 48.09% (95% CI, 40.26-57.43), while for the once-every-3-weeks cisplatin arm were 73.95% (95% CI, 66.93-81.70) and 56.76% (95% CI, 48.46-66.48), respectively; HR=1.44 (95% CI, 1.03-2.03), P=0.034. The 5-year OS was 43.60% (95% CI, 36.29-52.37) in the once-a-week cisplatin arm, and 50.55% (95% CI, 43.06-59.35) in the once-every-3-weeks cisplatin arm; P = 0.19. There was no difference in any grade or grade ≥ 3 late adverse events between the two arms, except for hearing dysfunction, which was significantly more common in patients who received high-dose cisplatin. ConclusionsLong term follow-up confirms that cisplatin at 100 mg/m2 administered once-every-3-weeks concurrently with radical radiation for LAHNSCC leads to superior locoregional control as compared to cisplatin 30 mg/m2 once-a-week and should remain one of the standard treatment options.

Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.

A mouse model of autoimmune inner ear disease without endolymphatic hydrops

Autoimmune inner ear disease (AIED) is an organ-specific disease characterized by irreversible, prolonged, and progressive hearing and equilibrium dysfunctions. The primary symptoms of AIED include asymmetric sensorineural hearing loss accompanied by vertigo, aural fullness, and tinnitus. AIED is divided into primary and secondary types. Research has been conducted using animal models of rheumatoid arthritis (RA), a cause of secondary AIED. However, current models are insufficient to accurately analyze vestibular function, and the mechanism underlying the onset of AIED has not yet been fully elucidated. Elucidation of the mechanism of AIED onset is urgently needed to develop effective treatments. In the present study, we analyzed the pathogenesis of vertigo in autoimmune diseases using a mouse model of type II collagen-induced RA. Auditory brain stem response analysis demonstrated that the RA mouse models exhibited hearing loss, which is the primary symptom of AIED. In addition, our vestibulo-oculomotor reflex analysis, which is an excellent vestibular function test, accurately captured vertigo symptoms in the RA mouse models. Moreover, our results revealed that the cause of hearing loss and vestibular dysfunction was not endolymphatic hydrops, but rather structural destruction of the organ of Corti and the lateral semicircular canal ampulla due to an autoimmune reaction against type II collagen. Overall, we were able to establish a mouse model of AIED without endolymphatic hydrops. Our findings will help elucidate the mechanisms of hearing loss and vertigo associated with AIED and facilitate the development of new therapeutic methods.

Hearing dysfunction heralds an increase in non-motor burden and a worse quality of life in Parkinson's disease: new insights from non-motor spectrum.

Sensorial non-motor symptoms (NMSs) in Parkinson's disease (PD) still lack appropriate investigation in clinical practice. This study aimed to assess if and to what extent auditory dysfunction is associated with other NMSs in PD and its impact on patient's quality of life (QoL). We selected patients with idiopathic PD, without other concomitant neurological diseases, dementia, or diagnosis of any audiological/vestibular disease. Demographic and clinical data were collected. Patients underwent otoscopic examination, audiological testing with pure tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAEs) and completed Non-Motor Symptoms Scale (NMSS) and Parkinson's Disease Questionnaires-39 (PDQ-39). ANCOVA and partial correlation analysis have been used for statistical analysis. 60 patients were enrolled and completed PTA and DPOAEs. 32 patients with hearing impairment (HI), assessed by PTA, (hearing threshold ≥ 25dB) showed similar disease duration, motor impairment, and staging, compared to patients without HI, but higher scores both in NMSS and in PDQ-39, except for cardiovascular (CV), gastrointestinal (GI), urogenital (U) and sexual function (SF) of NMSS. In addition, DPOAEs showed a significant correlation with higher scores both in NMSS and PDQ-39, except for CV, SF, GI, U and perceptual problem subdomains of NMSS. This study demonstrated that PD patients with HI have a greater burden of NMS and lower related QoL and functioning. Our results highlight the importance to reconsider HI as a NMS, in parallel with the others. HI evaluation, even in asymptomatic patients, may reveal a wider pathology with a worse QoL.

Early-Onset Hearing Loss in Mouse Models of Alzheimer's Disease and Increased DNA Damage in the Cochlea.

There is considerable interest in whether sensory deficiency is associated with the development of Alzheimer's disease (AD). Notably, the relationship between hearing impairment and AD is of high relevance but still poorly understood. In this study, we found early-onset hearing loss in two AD mouse models, 3xTgAD and 3xTgAD/Polβ+/-. The 3xTgAD/Polβ+/- mouse is DNA repair deficient and has more humanized AD features than the 3xTgAD. Both AD mouse models showed increased auditory brainstem response (ABR) thresholds between 16 and 32 kHz at 4 weeks of age, much earlier than any AD cognitive and behavioral changes. The ABR thresholds were significantly higher in 3xTgAD/Polβ+/- mice than in 3xTgAD mice at 16 kHz, and distortion product otoacoustic emission signals were reduced, indicating that DNA damage may be a factor underlying early hearing impairment in AD. Poly ADP-ribosylation and protein expression levels of DNA damage markers increased significantly in the cochlea of the AD mice but not in the adjacent auditory cortex. Phosphoglycerate mutase 2 levels and the number of synaptic ribbons in the presynaptic zones of inner hair cells were decreased in the cochlea of the AD mice. Furthermore, the activity of sirtuin 3 was downregulated in the cochlea of these mice, indicative of impaired mitochondrial function. Taken together, these findings provide new insights into potential mechanisms for hearing dysfunction in AD and suggest that DNA damage in the cochlea might contribute to the development of early hearing loss in AD.

The auditory phenotype of behavioural variant frontotemporal dementia

AbstractBackgroundPatients with behavioural variant frontotemporal dementia commonly exhibit abnormal hedonic and other behavioural responses to sounds, however hearing dysfunction in this disorder is poorly characterised. Here we addressed this issue using the Queen Square Tests of Auditory Cognition (QSTAC) – a neuropsychological battery for the systematic assessment of central auditory functions (including pitch pattern perception, environmental sound recognition, sound localisation and emotion processing) in cognitively impaired people.MethodThe QSTAC was administered to 15 patients with behavioural variant frontotempoal dementia, 24 patients with comparator dementia syndromes (primary progressive aphasia and typical Alzheimer’s disease) and 15 healthy age‐matched individuals. Participants also had pure tone audiometry to assess peripheral hearing function and a comprehensive general neuropsychological assessment.ResultAfter accounting for nonverbal executive and peripheral hearing performance, patients with behavioural variant frontotemporal dementia showed deficits of environmental sound and auditory emotion recognition and sound localisation, compared both with healthy controls and patients with Alzheimer’s disease. Patients with behavioural variant frontotemporal dementia were further differentiated from primary progressive aphasia patients on their performance across QSTAC (sound recognition and localisation) subtests.ConclusionBehavioural variant frontotemporal dementia has a distinct phenotype of auditory cognitive dysfunction which likely contributes to the hearing alterations that many patients with this diagnosis experience in daily life. Our findings call attention to an under‐recognised issue in frontotemporal dementia that warrants further clinical interpretation and the development of management strategies tailored to real‐world acoustic environments.

Ways of depicting speech deficits in the cinematic space: selected examples

The article discusses an important social aspect concerning speech disorders, also in people with disabilities, and the methods of their presentation in the film space. The main aim of the article is the way of presenting dysfunctions in the field of communication in a cinematic work. Other tasks of the article include attempts to answer the following questions: “does the environment influence the development of communication skills of people with disabilities?”, “how does the film show the relationships of people with speech disorders and disabilities in contacts with loved ones?”, and to “what extent is the film image consistent with the scientific description of a given disorder?”. The analytical chapters in the article are devoted to three disorders and selected feature films in which the actors present the language and communication skills of film characters struggling with speech disfluency, hearing dysfunction and cerebral palsy.

The proper timing of Atoh1 expression is pivotal for hair cell subtype differentiation and the establishment of inner ear function

Atoh1 overexpression is essential for hair cell (HC) regeneration in the sensory epithelium of mammalian auditory and vestibular organs. However, Atoh1 overexpression alone cannot induce fully mature and functional HCs in the mammalian inner ear. In the current study, we investigated the effect of Atoh1 constitutive overexpression in native HCs by manipulating Atoh1 expression at different developmental stages. We demonstrated that constitutive overexpression of Atoh1 in native vestibular HCs did not affect cell survival but did impair vestibular function by interfering with the subtype differentiation of HCs and hair bundle development. In contrast, Atoh1 overexpression in cochlear HCs impeded their maturation, eventually leading to gradual HC loss in the cochlea and hearing dysfunction. Our study suggests that time-restricted Atoh1 expression is essential for the differentiation and survival of HCs in the inner ear, and this is pivotal for both hearing and vestibular function re-establishment through Atoh1 overexpression-induced HC regeneration strategies.

RIPOR2: A new gene of non-syndromic cochleovestibular dysfunction, discrepancy between human pathology and animal models.

Cochleovestibular dysfunctions are rare conditions misrecognized. A homozygous pathogenic variation c.1561C > T (p.Arg521*) in RIPOR2 (RHO family interacting cell polarization regulator 2) has been identified by WES in Tunisian siblings suffering from congenital bilateral profound hearing and vestibular dysfunctions. In contrast to the vestibular areflexia observed in our patients, deaf Ripor2 KO mouse model and our zebrafish model have normal vestibular function.

Glutamate excitotoxicity in the cochlea

Glutamate excitotoxicity in the cochlea Mark Rutherford, Associate Professor at Washington University School of Medicine, discusses the burden and causes of hearing dysfunction, as well as the possible solutions for mitigating glutamate excitotoxicity. The cochlea, the snail-shaped organ of the inner ear located deep in the skull, contains approximately 15,000 sound receptors called sensory ‘hair cells’ and approximately 50,000 nerve fibers sending sound information to the brain. Although that may seem like a lot, it is not compared to the approximately 100 billion neurons in the brain. These hair cells and nerve fibers are all we get for life, and they are gradually lost over time due to aging. Unfortunately, environmental factors accelerate cochlear decline over time. One of those environmental factors is loud sounds.Today, we live in an environment of sound at levels that far exceed those under which our species evolved, especially those of us with noisy occupations or recreational activities. For example, military personnel are particularly vulnerable to hearing loss, making hearing disorders (including tinnitus) the number one disability claim of the U.S. Veterans Administration.

Features of speech signal recognition in conditions of vocal competition with normal hearing and with hearing or speech disorders

We studied the features of speech signals perception in conditions of vocal competition based on gender (male/female voice) in subjects of different ages and status of auditory and speech functions. Psychophysical measurements were carried out while simulating a “speech cocktail” situation by simultaneously pronounced different words by a male and female. The average fundamental voice frequency for the male speaker was 108 ± 5.92 Hz, for the female speaker – 185 ± 12.03 Hz. Both speakers were standard native speakers of the Russian language. Digital recordings of speech signals were equalized in intensity and compounded so that the total test stimulus was a synchronized mixture of words spoken by a male (M) and female (F) voice. Test speech signals were presented through headphones or through a speaker located in front of the auditor at a distance of 50 cm. The indicators of reaction time and the number of correct recognitions of words of the target speaker (M or F) were compared in 4 groups of subjects of different ages and hearing or speech status: adult subjects with normal hearing and speech (n = 35) and with hearing impaired (n = 26); schoolchildren with normotypical development (n = 26) and with speech disorders (n = 25). The results indicated a falling in the ability to segrerate target speech streams under conditions of vocal competition in the subjects with hearing and speech dysfunctions included in the comparative study. Differences in the perception of male and female voices in subjects with hearing loss and with speech problems were obtained. This result may have a biological and social basis. The data have practical significance for the development of a system of auditory and speech training and modern hearing aid technologies.

The enduring importance of comparative models for understanding hearing loss

Comparative hearing research has historically focused on diverse organisms’ solutions to sensory problems such as localizing sounds in space, responding to conspecific vocalizations, and using sound for navigation and prey capture. These studies have advanced the bioacoustics and auditory neuroscience fields for many decades, despite decreasing funding for comparative auditory research whose primary intent is not to model human communication disorders. However, animals from across many taxa can experience hearing loss, and to varying degrees, recover their hearing abilities after exposure to damaging events. The genetic diversity of these animals, species-specific variations in evolved protective mechanisms, the rich repertoire of acoustic behaviors, and differences in the capacity for self-repair present important opportunities for discovery of the fundamental mechanisms of normal and disordered hearing. No one species best models humans. It is critical that we support and promote analysis of the physiological, anatomical, and behavioral manifestations of hearing loss using a comparative approach. This presentation will highlight some of the opportunities and challenges in working with diverse species as models of hearing dysfunction.