Intracochlear Recording of Electrocochleography During and After Cochlear Implant Insertion Dependent on the Location in the Cochlea.

To preserve residual hearing during cochlear implant (CI) surgery it is desirable to use intraoperative monitoring of inner ear function (cochlear monitoring). A promising method is electrocochleography (ECochG). Within this project the relations between intracochlear ECochG recordings, position of the recording contact in the cochlea with respect to anatomy and frequency and preservation of residual hearing were investigated. The aim was to better understand the changes in ECochG signals and whether these are due to the electrode position in the cochlea or to trauma generated during insertion. During and after insertion of hearing preservation electrodes, intraoperative ECochG recordings were performed using the CI electrode (MED-EL). During insertion, the recordings were performed at discrete insertion steps on electrode contact 1. After insertion as well as postoperatively the recordings were performed at different electrode contacts. The electrode location in the cochlea during insertion was estimated by mathematical models using preoperative clinical imaging, the postoperative location was measured using postoperative clinical imaging. The recordings were analyzed from six adult CI recipients. In the four patients with good residual hearing in the low frequencies the signal amplitude rose with largest amplitudes being recorded closest to the generators of the stimulation frequency, while in both cases with severe pantonal hearing losses the amplitude initially rose and then dropped. This might be due to various reasons as discussed in the following. Our results indicate that this approach can provide valuable information for the interpretation of intracochlearly recorded ECochG signals.

Extending Subcortical EEG Responses to Continuous Speech to the Sound-Field.

The auditory brainstem response (ABR) is a valuable clinical tool for objective hearing assessment, which is conventionally detected by averaging neural responses to thousands of short stimuli. Progressing beyond these unnatural stimuli, brainstem responses to continuous speech presented via earphones have been recently detected using linear temporal response functions (TRFs). Here, we extend earlier studies by measuring subcortical responses to continuous speech presented in the sound-field, and assess the amount of data needed to estimate brainstem TRFs. Electroencephalography (EEG) was recorded from 24 normal hearing participants while they listened to clicks and stories presented via earphones and loudspeakers. Subcortical TRFs were computed after accounting for non-linear processing in the auditory periphery by either stimulus rectification or an auditory nerve model. Our results demonstrated that subcortical responses to continuous speech could be reliably measured in the sound-field. TRFs estimated using auditory nerve models outperformed simple rectification, and 16 minutes of data was sufficient for the TRFs of all participants to show clear wave V peaks for both earphones and sound-field stimuli. Subcortical TRFs to continuous speech were highly consistent in both earphone and sound-field conditions, and with click ABRs. However, sound-field TRFs required slightly more data (16 minutes) to achieve clear wave V peaks compared to earphone TRFs (12 minutes), possibly due to effects of room acoustics. By investigating subcortical responses to sound-field speech stimuli, this study lays the groundwork for bringing objective hearing assessment closer to real-life conditions, which may lead to improved hearing evaluations and smart hearing technologies.

Impact of Hearing Aids on Language Outcomes in Preschool Children With Mild Bilateral Hearing Loss.

This study aimed to investigate the role of hearing aid (HA) usage in language outcomes among preschool children aged 3-5 years with mild bilateral hearing loss (MBHL). The data were retrieved from a total of 52 children with MBHL and 30 children with normal hearing (NH). The association between demographical, audiological factors and language outcomes was examined. Analyses of variance were conducted to compare the language abilities of HA users, non-HA users, and their NH peers. Furthermore, regression analyses were performed to identify significant predictors of language outcomes. Aided better ear pure-tone average (BEPTA) was significantly correlated with language comprehension scores. Among children with MBHL, those who used HA outperformed the ones who did not use HA across all linguistic domains. The language skills of children with MBHL were comparable to those of their peers with NH. The degree of improvement in audibility in terms of aided BEPTA was a significant predictor of language comprehension. It is noteworthy that 50% of the parents expressed reluctance regarding HA use for their children with MBHL. The findings highlight the positive impact of HA usage on language development in this population. Professionals may therefore consider HAs as a viable treatment option for children with MBHL, especially when there is a potential risk of language delay due to hearing loss. It was observed that 25% of the children with MBHL had late-onset hearing loss. Consequently, the implementation of preschool screening or a listening performance checklist is recommended to facilitate early detection.

Relationship Between Hypertension and Hearing Loss: Analysis of the Related Factors.

Purpose: The impact of hypertension extends to hearing loss, aging, and mental Health. The purpose of this study was to investigate the characteristics of hearing loss and hearing thresholds at different frequencies in individuals with hypertension. Through a comprehensive analysis, in the present study, it aimed to uncover the contributing factors that underlie hearing loss in this patient cohort, shedding light on the complex relationship between hypertension and auditory impairment. Patients and Methods: This was a single-center population-based observational study, and clinical, biological, and hospital data were collected from the inpatient ward. In the present study, 517 patients (1034 ears) with or without hypertension were included, and the proportion of patients with hearing loss, mean pure-tone average hearing threshold, low-frequency pure-tone average hearing threshold (LFPTA), medium-frequency pure-tone average hearing threshold (MFPTA) and high-frequency pure-tone average hearing threshold (HFPTA) were evaluated. Risk factors related to hearing loss and hearing threshold were also estimated at different frequencies. Results: The proportion of patients with hearing loss was higher in the hypertensive group than in the nonhypertensive group (P<0.05). After including risk factors for cardiovascular disease that can have an impact on the parameters of hearing and ambulatory blood pressure in the regression model, factors related to hearing loss included the albumin-to-creatinine ratio (ACR) and the standard deviation of the 24-hour systolic blood pressure (24h-SSD). ACR, 24h-SSD, and day systolic blood pressure (Day SBP) were associated with the mean pure-tone average hearing threshold, LFPTA, MFPTA, and HFPTA. The area under the receiver operating characteristic curve of ACR + 24h-SSD for hearing loss was 0.873, with a sensitivity of 86.73%, specificity of 90.52%, and a 95% confidence interval of 0.821-0.914. Conclusion: Hypertension is correlated with hearing loss, and the combination of ACR and 24h-SSD demonstrates an improved predictive capacity for hearing loss in hypertensive patients.

Frequency-dependent temporary threshold shifts in the Eastern painted turtle (Chrysemys picta picta).

Testudines are a highly threatened group facing an array of stressors, including alteration of their sensory environment. Underwater noise pollution has the potential to induce hearing loss and disrupt detection of biologically important acoustic cues and signals. To examine the conditions that induce temporary threshold shifts (TTS) in hearing in the freshwater Eastern painted turtle (Chrysemys picta picta), three individuals were exposed to band limited continuous white noise (50-1000 Hz) of varying durations and amplitudes (sound exposure levels ranged from 151 to 171 dB re 1 µPa2 s). Control and post-exposure auditory thresholds were measured and compared at 400 and 600 Hz using auditory evoked potential methods. TTS occurred in all individuals at both test frequencies, with shifts of 6.1-41.4 dB. While the numbers of TTS occurrences were equal between frequencies, greater shifts were observed at 600 Hz, a frequency of higher auditory sensitivity, compared to 400 Hz. The onset of TTS occurred at 154 dB re 1 µPa2 s for 600 Hz, compared to 158 dB re 1 µPa2 s at 400 Hz. The 400-Hz onset and patterns of TTS growth and recovery were similar to those observed in previously studied Trachemys scripta elegans, suggesting TTS may be comparable across Emydidae species.

Effects of spatial configuration and fundamental frequency on speech intelligibility in multiple-talker conditions in the ipsilateral horizontal plane and median planea).

Spatial separation and fundamental frequency (F0) separation are effective cues for improving the intelligibility of target speech in multi-talker scenarios. Previous studies predominantly focused on spatial configurations within the frontal hemifield, overlooking the ipsilateral side and the entire median plane, where localization confusion often occurs. This study investigated the impact of spatial and F0 separation on intelligibility under the above-mentioned underexplored spatial configurations. The speech reception thresholds were measured through three experiments for scenarios involving two to four talkers, either in the ipsilateral horizontal plane or in the entire median plane, utilizing monotonized speech with varying F0s as stimuli. The results revealed that spatial separation in symmetrical positions (front-back symmetry in the ipsilateral horizontal plane or front-back, up-down symmetry in the median plane) contributes positively to intelligibility. Both target direction and relative target-masker separation influence the masking release attributed to spatial separation. As the number of talkers exceeds two, the masking release from spatial separation diminishes. Nevertheless, F0 separation remains as a remarkably effective cue and could even facilitate spatial separation in improving intelligibility. Further analysis indicated that current intelligibility models encounter difficulties in accurately predicting intelligibility in scenarios explored in this study.

An Exploration of the Memory Performance in Older Adult Hearing Aid Users on the Integrated Digit-in-Noise Test.

This study aimed to preliminarily investigate the associations between performance on the integrated Digit-in-Noise Test (iDIN) and performance on measures of general cognition and working memory (WM). The study recruited 81 older adult hearing aid users between 60 and 95 years of age with bilateral moderate to severe hearing loss. The Chinese version of the Montreal Cognitive Assessment Basic (MoCA-BC) was used to screen older adults for mild cognitive impairment. Speech reception thresholds (SRTs) were measured using 2- to 5-digit sequences of the Mandarin iDIN. The differences in SRT between five-digit and two-digit sequences (SRT5-2), and between five-digit and three-digit sequences (SRT5-3), were used as indicators of memory performance. The results were compared to those from the Digit Span Test and Corsi Blocks Tapping Test, which evaluate WM and attention capacity. SRT5-2 and SRT5-3 demonstrated significant correlations with the three cognitive function tests (rs ranging from -.705 to -.528). Furthermore, SRT5-2 and SRT5-3 were significantly higher in participants who failed the MoCA-BC screening compared to those who passed. The findings show associations between performance on the iDIN and performance on memory tests. However, further validation and exploration are needed to fully establish its effectiveness and efficacy.

Does Intraoperative Extracochlear Electrocochleography Correlate With Postoperative Audiometric Hearing Thresholds in Cochlear Implant Surgery? A Retrospective Analysis of Cochlear Monitoring.

In recent years, tools for early detection of irreversible trauma to the basilar membrane during hearing preservation cochlear implant (CI) surgery were established in several clinics. A link with the degree of postoperative hearing preservation in patients was investigated, but patient populations were usually small. Therefore, this study's aim was to analyze data from intraoperative extracochlear electrocochleography (ECochG) recordings for a larger group.During hearing preservation CI surgery, extracochlear recordings were made before, during, and after CI electrode insertion using a cotton wick electrode placed at the promontory. Before and after insertion, amplitudes and stimulus response thresholds were recorded at 250, 500, and 1000 Hz. During insertion, response amplitudes were recorded at one frequency and one stimulus level. Data from 121 patient ears were analyzed.The key benefit of extracochlear recordings is that they can be performed before, during, and after CI electrode insertion. However, extracochlear ECochG threshold changes before and after CI insertion were relatively small and did not independently correlate well with hearing preservation, although at 250 Hz they added some significant information. Some tendencies-although no significant relationships-were detected between amplitude behavior and hearing preservation. Rising amplitudes seem favorable and falling amplitudes disadvantageous, but constant amplitudes do not appear to allow stringent predictions.Extracochlear ECochG measurements seem to only partially realize expected benefits. The questions now are: do gains justify the effort, and do other procedures or possible combinations lead to greater benefits for patients?

Alpha9alpha10 knockout mice show altered physiological and behavioral responses to signals in masking noise.

Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.

Towards ASSR-based hearing assessment using natural sounds.

Objective. The auditory steady-state response (ASSR) allows estimation of hearing thresholds. The ASSR can be estimated from electroencephalography (EEG) recordings from electrodes positioned on both the scalp and within the ear (ear-EEG). Ear-EEG can potentially be integrated into hearing aids, which would enable automatic fitting of the hearing device in daily life. The conventional stimuli for ASSR-based hearing assessment, such as pure tones and chirps, are monotonous and tiresome, making them inconvenient for repeated use in everyday situations. In this study we investigate the use of natural speech sounds for ASSR estimation.Approach.EEG was recorded from 22 normal hearing subjects from both scalp and ear electrodes. Subjects were stimulated monaurally with 180 min of speech stimulus modified by applying a 40 Hz amplitude modulation (AM) to an octave frequency sub-band centered at 1 kHz. Each 50 ms sub-interval in the AM sub-band was scaled to match one of 10 pre-defined levels (0-45 dB sensation level, 5 dB steps). The apparent latency for the ASSR was estimated as the maximum average cross-correlation between the envelope of the AM sub-band and the recorded EEG and was used to align the EEG signal with the audio signal. The EEG was then split up into sub-epochs of 50 ms length and sorted according to the stimulation level. ASSR was estimated for each level for both scalp- and ear-EEG.Main results. Significant ASSRs with increasing amplitude as a function of presentation level were recorded from both scalp and ear electrode configurations.Significance. Utilizing natural sounds in ASSR estimation offers the potential for electrophysiological hearing assessment that are more comfortable and less fatiguing compared to existing ASSR methods. Combined with ear-EEG, this approach may allow convenient hearing threshold estimation in everyday life, utilizing ambient sounds. Additionally, it may facilitate both initial fitting and subsequent adjustments of hearing aids outside of clinical settings.

Pediatric normative data for a novel and fast speech perception test in noise.

OBJECTIVES: Communicating in noisy settings can be difficult due to interference and environmental noise, which can impact intelligibility for those with hearing impairments and those with normal hearing threshold. Speech intelligibility is commonly assessed in audiology through speech audiometry in quiet environments. Nevertheless, this test may not effectively assess hearing challenges in noisy environments, as total silence is rare in daily activities. A recently patented method, known as the SRT50 FAST, has been developed for conducting speech audiometry in noise. This new method enables the acceleration and simplification of free field speech audiometry tests involving competition noise. This study aims to establish normative scores and standardize the SRT50 FAST method as a test for evaluating speech perception in noise in pediatric patients. METHODS: The study included 30 participants with normal hearing, consisting of 11 females and 19 males, ranging in age from 6 to 11 years. A series of speech audiometry tests were conducted to determine the speech reception threshold 50% (SRT50) in competing conditions. This included testing both the fast mode (SRT50 FAST) currently being studied and the traditional method (SRT50 CLASSIC). The SRT50, or Signal to Noise Ratio (SNR) at which 50% of speech recognition occurred, was investigated for both methods. RESULTS: The mean SRT50 FAST test score was -2.69 (SD = 3.15). The dataset exhibited a normal distribution with values ranging from 3.60 to -8.60. Since the scores are expressed in SRT, higher scores indicate poorer performance. We have established a threshold of 3.60 as the upper limit of the normal range, therefore, patients with scores above this threshold are considered to have abnormal results. CONCLUSIONS: This study aimed to establish normative data for the evaluation of free field speech in noise recognition using the SRT50 FAST method in the pediatric population. This method accurately investigates the necessary signal-to-noise ratio for achieving 50% recognition scores with bisyllabic words in a quick manner. The ultimate objective is to employ this test to identify the optimal configuration of hearing rehabilitation devices, particularly for pediatric patients with hearing aids and/or cochlear implants. Additionally, it can be used to assess pediatric patients with unilateral hearing loss.

Hearing and vocalizations in a small songbird, the red-cheeked cordon bleu (Uraeginthus bengalus) (L).

The auditory sensitivity of a small songbird, the red-cheeked cordon bleu, was measured using the standard methods of animal psychophysics. Hearing in cordon bleus is similar to other small passerines with best hearing in the frequency region from 2 to 4 kHz and sensitivity declining at the rate of about 10 dB/octave below 2 kHz and about 35 dB/octave as frequency increases from 4 to 9 kHz. While critical ratios are similar to other songbirds, the long-term average power spectrum of cordon bleu song falls above the frequency of best hearing in this species.

Electrocochleographic frequency-following responses as a potential marker of age-related cochlear neural degeneration.

Auditory nerve (AN) fibers that innervate inner hair cells in the cochlea degenerate with advancing age. It has been proposed that age-related reductions in brainstem frequency-following responses (FFR) to the carrier of low-frequency, high-intensity pure tones may partially reflect this neural loss in the cochlea (Märcher-Rørsted et al., 2022). If the loss of AN fibers is the primary factor contributing to age-related changes in the brainstem FFR, then the FFR could serve as an indicator of cochlear neural degeneration. In this study, we employed electrocochleography (ECochG) to investigate the effects of age on frequency-following neurophonic potentials, i.e., neural responses phase-locked to the carrier frequency of the tone stimulus. We compared these findings to the brainstem-generated FFRs obtained simultaneously using the same stimulation. We conducted recordings in young and older individuals with normal hearing. Responses to pure tones (250 ms, 516 and 1086 Hz, 85 dB SPL) and clicks were recorded using both ECochG at the tympanic membrane and traditional scalp electroencephalographic (EEG) recordings of the FFR. Distortion product otoacoustic emissions (DPOAE) were also collected. In the ECochG recordings, sustained AN neurophonic (ANN) responses to tonal stimulation, as well as the click-evoked compound action potential (CAP) of the AN, were significantly reduced in the older listeners compared to young controls, despite normal audiometric thresholds. In the EEG recordings, brainstem FFRs to the same tone stimulation were also diminished in the older participants. Unlike the reduced AN CAP response, the transient-evoked wave-V remained unaffected. These findings could indicate that a decreased number of AN fibers contributes to the response in the older participants. The results suggest that the scalp-recorded FFR, as opposed to the clinical standard wave-V of the auditory brainstem response, may serve as a more reliable indicator of age-related cochlear neural degeneration.

Age Impacts Speech-in-Noise Recognition Differently for Nonnative and Native Listeners.

PURPOSE: The purpose of this study was to explore potential differences in suprathreshold auditory function among native and nonnative speakers of English as a function of age. METHOD: Retrospective analyses were performed on three large data sets containing suprathreshold auditory tests completed by 5,572 participants who were self-identified native and nonnative speakers of English between the ages of 18-65 years, including a binaural tone detection test, a digit identification test, and a sentence recognition test. RESULTS: The analyses show a significant interaction between increasing age and participant group on tests involving speech-based stimuli (digit strings, sentences) but not on the binaural tone detection test. For both speech tests, differences in speech recognition emerged between groups during early adulthood, and increasing age had a more negative impact on word recognition for nonnative compared to native participants. Age-related declines in performance were 2.9 times faster for digit strings and 3.3 times faster for sentences for nonnative participants compared to native participants. CONCLUSIONS: This set of analyses extends the existing literature by examining interactions between aging and self-identified native English speaker status in several auditory domains in a cohort of adults spanning young adulthood through middle age. The finding that older nonnative English speakers in this age cohort may have greater-than-expected deficits on speech-in-noise perception may have clinical implications on how these individuals should be diagnosed and treated for hearing difficulties.

A single dose of AC102 restores hearing in a guinea pig model of noise-induced hearing loss to almost prenoise levels.

Although sudden sensorineural hearing loss (SSNHL) is a serious condition, there are currently no approved drugs for its treatment. Nevertheless, there is a growing understanding that the cochlear pathologies that underlie SSNHL include apoptotic death of sensory outer hair cells (OHCs) as well as loss of ribbon synapses connecting sensory inner hair cells (IHCs) and neurites of the auditory nerve, designated synaptopathy. Noise-induced hearing loss (NIHL) is a common subtype of SSNHL and is widely used to model hearing loss preclinically. Here, we demonstrate that a single interventive application of a small pyridoindole molecule (AC102) into the middle ear restored auditory function almost to prenoise levels in a guinea pig model of NIHL. AC102 prevented noise-triggered loss of OHCs and reduced IHC synaptopathy suggesting a role of AC102 in reconnecting auditory neurons to their sensory target cells. Notably, AC102 exerted its therapeutic properties over a wide frequency range. Such strong improvements in hearing have not previously been demonstrated for other therapeutic agents. In vitro experiments of a neuronal damage model revealed that AC102 protected cells from apoptosis and promoted neurite growth. These effects may be explained by increased production of adenosine triphosphate, indicating improved mitochondrial function, and reduced levels of reactive-oxygen species which prevents the apoptotic processes responsible for OHC death. This action profile of AC102 might be causal for the observed hearing recovery in in vivo models.

On the Feasibility of Using Behavioral Listening Effort Test Methods to Evaluate Auditory Performance in Cochlear Implant Users.

Realistic outcome measures that reflect everyday hearing challenges are needed to assess hearing aid and cochlear implant (CI) fitting. Literature suggests that listening effort measures may be more sensitive to differences between hearing-device settings than established speech intelligibility measures when speech intelligibility is near maximum. Which method provides the most effective measurement of listening effort for this purpose is currently unclear. This study aimed to investigate the feasibility of two tests for measuring changes in listening effort in CI users due to signal-to-noise ratio (SNR) differences, as would arise from different hearing-device settings. By comparing the effect size of SNR differences on listening effort measures with test-retest differences, the study evaluated the suitability of these tests for clinical use. Nineteen CI users underwent two listening effort tests at two SNRs (+4 and +8 dB relative to individuals' 50% speech perception threshold). We employed dual-task paradigms-a sentence-final word identification and recall test (SWIRT) and a sentence verification test (SVT)-to assess listening effort at these two SNRs. Our results show a significant difference in listening effort between the SNRs for both test methods, although the effect size was comparable to the test-retest difference, and the sensitivity was not superior to speech intelligibility measures. Thus, the implementations of SVT and SWIRT used in this study are not suitable for clinical use to measure listening effort differences of this magnitude in individual CI users. However, they can be used in research involving CI users to analyze group data.

[Mechanism of noise induced hidden hearing loss based on proteomics].

Objective: To explore the mechanism of noise-induced hidden hearing loss by proteomics. Methods: In October 2022, 64 SPF male C57BL/6J mice were divided into control group and noise exposure group with 32 mice in each group according to random sampling method. The noise exposure group was exposed to 100 dB sound pressure level, 2000-16000 Hz broadband noise for 2 h, and the mouse hidden hearing loss model was established. Auditory brainstem response (ABR) was used to test the change of hearing threshold of mice on the 7th day after noise exposure, the damage of basal membrane hair cells was observed by immunofluorescence, and the differentially expressed proteins in the inner ear of mice in each group were identified and analyzed by 4D-Label-free quantitative proteomics, and verified by Western blotting. The results were statistically analyzed by ANOVA and t test. Results: On the 7th day after noise exposure, there was no significant difference in hearing threshold between the control group and the noise exposure group at click and 8000 Hz acoustic stimulation (P>0.05) . The hearing threshold in the noise exposure group was significantly higher than that in the control group under 16000 Hz acoustic stimulation (P<0.05) . Confocal immunofluorescence showed that the basal membrane hair cells of cochlear tissue in noise exposure group were arranged neatly, but the relative expression of C-terminal binding protein 2 antibody of presynaptic membrane in middle gyrus and basal gyrus was significantly lower than that in control group (P<0.05) . GO enrichment analysis showed that the functions of differentially expressed proteins were mainly concentrated in membrane potential regulation, ligand-gated channel activity, and ligand-gated ion channel activity. KEGG pathway enrichment analysis showed that differentially expressed proteins were significantly enriched in phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) signaling pathway, NOD-like receptor signaling pathway, calcium signaling pathway, etc. Western blotting showed that the expression of inositol 1, 4, 5-trisphosphate receptor 3 (Itpr3) was increased and the expression of solute carrier family 38 member 2 (Slc38a2) was decreased in the noise exposure group (P<0.05) . Conclusion: Through proteomic analysis, screening and verification of the differential expression proteins Itpr3 and Slc38a2 in the constructed mouse noise-induced hidden hearing loss model, the glutaminergic synaptic related pathways represented by Itpr3 and Slc38a2 may be involved in the occurrence of hidden hearing loss.

L-Ergothioneine slows the progression of age-related hearing loss in CBA/CaJ mice.

The naturally occurring amino acid, l-ergothioneine (EGT), has immense potential as a therapeutic, having shown promise in the treatment of other disease models, including neurological disorders. EGT is naturally uptaken into cells via its specific receptor, OCTN1, to be utilized by cells as an antioxidant and anti-inflammatory. In our current study, EGT was administered over a period of 6 months to 25-26-month-old CBA/CaJ mice as a possible treatment for age-related hearing loss (ARHL), since presbycusis has been linked to higher levels of cochlear oxidative stress, apoptosis, and chronic inflammation. Results from the current study indicate that EGT can prevent aging declines of some key features of ARHL. However, we found a distinct sex difference for the response to the treatments, for hearing - Auditory Brainstem Responses (ABRs) and Distortion Product Otoacoustic Emissions (DPOAEs). Males exhibited lower threshold declines in both low dose (LD) and high dose (HD) test groups throughout the testing period and did not display some of the characteristic aging declines in hearing seen in Control animals. In contrast, female mice did not show any therapeutic effects with either treatment dose. Further confirming this sex difference, EGT levels in whole blood sampling throughout the testing period showed greater uptake of EGT in males compared to females. Additionally, RT-PCR results from three tissue types of the inner ear confirmed EGT activity in the cochlea in both males and females. Males and females exhibited significant differences in biomarkers related to apoptosis (Cas-3), inflammation (TNF-a), oxidative stress (SOD2), and mitochondrial health (PGC1a).These changes were more prominent in males as compared to females, especially in stria vascularis tissue. Taken together, these findings suggest that EGT has the potential to be a naturally derived therapeutic for slowing down the progression of ARHL, and possibly other neurodegenerative diseases. EGT, while effective in the treatment of some features of presbycusis in aging males, could also be modified into a general prophylaxis for other age-related disorders where treatment protocols would include eating a larger proportion of EGT-rich foods or supplements. Lastly, the sex difference discovered here, needs further investigation to see if therapeutic conditions can be developed where aging females show better responsiveness to EGT.

Assessing the accuracy and reliability of application-based audiometry for hearing evaluation.

Pure-tone audiometry (PTA) is the gold standard for assessing hearing loss. However, traditional PTA tests require specialized equipment, trained personnel, and a soundproof environment. Recently, smartphone-based PTA tests have been developed as an alternative method for hearing assessment. The aim of this study was to validate the accuracy and reliability of a smartphone application-based audiometry test. This study was conducted to assess the performance of application-based audiometry from November 2021 to January 2022. Pure-tone thresholds were measured using a smartphone application-based PTA test and compared with results obtained using a traditional audiometer in a sound-treated booth. The smartphone application used in this study was the "Care4Ear (Care4ear, version 1.0.6, MIJ Co., Ltd.)". Hearing thresholds less than 35 dB HL were classified as group A, 35-64 dB HL as group B, and 65 dB HL or greater as group C for the classification of hearing levels. We evaluated the accuracy of smartphone audiometry for each group and compared the results of frequency-specific hearing tests. Additionally, we examined the results of smartphone audiometry in individuals (n = 27) with asymmetric hearing loss. Seventy subjects completed both conventional audiometry and smartphone application-based hearing tests. Among the ears assessed, 55.7% were classified as group A, while 25.7% and 18.6% were classified as group B and group C, respectively. The average hearing threshold obtained from conventional pure-tone audiometry was 37.7 ± 25.2 dB HL, whereas the application-based hearing test yielded thresholds of 21.0 ± 23.0 dB HL. A significant correlation (r = 0.69, p < 0.01) was found between the average hearing thresholds obtained from the application-based and conventional pure-tone audiometry tests. The application-based test achieved a 97.4% hit rate for classifying hearing thresholds as class A, but lower rates of 22.2% for class B and 38.5% for class C. Notably, a discrepancy was observed between the hearing threshold measured by the application and the conventional audiometry for the worse ear with asymmetric hearing. The smartphone-based audiometry is a feasible method for hearing evaluation especially in persons with normal hearing. In cases of hearing loss or asymmetric hearing loss, the results of the application-based audiometry may be inaccurate, limiting its diagnostic utility.

Noise-induced synaptic loss and its post-exposure recovery in CBA/CaJ vs. C57BL/6J mice.

Acute noise-induced loss of synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs) has been documented in several strains of mice, but the extent of post-exposure recovery reportedly varies dramatically. If such inter-strain heterogeneity is real, it could be exploited to probe molecular pathways mediating neural remodeling in the adult cochlea. Here, we compared synaptopathy repair in CBA/CaJ vs. C57BL/6J, which are at opposite ends of the reported recovery spectrum. We evaluated C57BL/6J mice 0 h, 24 h, 2 wks or 8 wks after exposure for 2 h to octave-band noise (8-16 kHz) at either 90, 94 or 98 dB SPL, to compare with analogous post-exposure results in CBA/CaJ at 98 or 101 dB. We counted pre- and post-synaptic puncta in immunostained cochleas, using machine learning to classify paired (GluA2 and CtBP2) vs. orphan (CtBP2 only) puncta, and batch-processing to quantify immunostaining intensity. At 98 dB, both strains show ongoing loss of ribbons and synapses between 0 and 24 h, followed by partial recovery, however the extent and degree of these changes were greater in C57BL/6J. Much of the synaptic recovery is due to transient reduction in GluA2 intensity in synaptopathic regions. In contrast, CtBP2 intensity showed only transient increases (at 2 wks). Neurofilament staining revealed transient extension of ANF terminals in C57BL/6J, but not in CBA/CaJ, peaking at 24 h and reverting by 2 wks. Thus, although interstrain differences in synapse recovery are dominated by reversible changes in GluA2 receptor levels, the neurite extension seen in C57BL/6J suggests a qualitative difference in regenerative capacity.