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.

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.

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.

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.

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.

Standard and Extend High-Frequency Audiometry in Sudden Sensorineural Hearing Loss: Impacts on Tinnitus and Mental Health.

OBJECTIVE: To analyze the results of auditory assessment in standard (SA) and extended high-frequency (EHF) audiometry, associating the findings with sudden tinnitus and mental health of patients with unilateral sudden sensorineural hearing loss (SSNHL). STUDY DESIGN: Prospective, cohort study. SETTING: Outpatient otology clinic in a tertiary care hospital. SUBJECTS AND METHODS: Patients experiencing unilateral SSNHL were evaluated with pure-tone audiometry performed at frequencies of 250 to16,000 Hz, tinnitus pitch and loudness matching tests, Tinnitus Handicap Inventory (THI), Analog and Visual Scale (AVS) for bothersome tinnitus, and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Eighteen patients with unilateral SSNHL were assessed. After starting treatment, there was a significant improvement in the SA (71.1 dB to 50 dB; p < 0.001*) and EHF audiometry (64.5 dB to 54.4 dB; p < 0.001*) thresholds at 15 days, and this persisted at 30 days of follow-up. Significant improvements were seen for tinnitus in loudness, VAS, and THI and for mental health in the realms of anxiety and depression by HADS. Despite improvements in SA, persistent EHF hearing loss was accompanied by persistent tinnitus, but it was of diminished loudness. CONCLUSION: Despite improvement in pure-tone thresholds by SA, a subset of unilateral SSNHL patients did not experience hearing recovery in EHF thresholds and reported persistent tinnitus. We postulate that their diminished anxiety and better mental health may be related to both hearing improvement in standard audiometry and reduction in tinnitus loudness. This pilot prospective study investigates the utility of performing EHF audiometry to better understand outcomes in patients with SSNHL.

Does coronavirus disease 2019 affect peripheral and central auditory systems? Matched group cross-sectional study and six-month follow up.

OBJECTIVE: This study aimed to compare the peripheral-to-central auditory systems of people with coronavirus disease 2019 to a well-matched control group and examine the long-term effects of coronavirus disease 2019 on the auditory system. METHOD: Participants who were outpatients of coronavirus disease 2019 (n = 30) were compared with a well-matched control group (n = 30). Behavioural and electrophysiological tests were performed, and tests were repeated at six months in the coronavirus disease 2019 group. RESULTS: Statistically significant differences were observed in the right ear at 10 kHz (p = 0.007) and 12.5 kHz (p = 0.028), and in the left ear at 10 kHz (p = 0.040) and 12.5 kHz (p = 0.040) between groups. The groups had no difference regarding the other audiological test results (p > 0.05). CONCLUSION: Extended high-frequency thresholds were affected in the coronavirus disease 2019 patients. No other findings indicated that the peripheral-to-central auditory system was affected. The effect on extended high-frequency thresholds appeared permanent, but no clinically significant new, late-onset auditory system effects were observed.

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.

Correlation Analysis and Comparison of Adult CE-Chirp ABR Response Threshold and Pure Tone Hearing Threshold.

OBJECTIVES: To study the application of CE-Chirp in the evaluation of hearing impairment in forensic medicine by testing the auditory brainstem response (ABR) in adults using CE-Chirp to analyze the relationship between the V-wave response threshold of CE-Chirp ABR test and the pure tone hearing threshold. METHODS: Subjects (aged 20-77 with a total of 100 ears) who underwent CE-Chirp ABR test in Changzhou De'an Hospital from January 2018 to June 2019 were selected to obtain the V-wave response threshold, and pure tone air conduction hearing threshold tests were conducted at 0.5, 1.0, 2.0 and 4.0 kHz, respectively, to obtain pure tone listening threshold. The differences and statistical differences between the average pure tone hearing threshold and V-wave response threshold were compared in different hearing levels and different age groups. The correlation, differences and statistical differences between the two tests at each frequency were analyzed for all subjects. The linear regression equation for estimating pure tone hearing threshold for all subjects CE-Chirp ABR V-wave response threshold was established, and the feasibility of the equation was tested. RESULTS: There was no statistical significance in the CE-Chirp ABR response threshold and pure tone hearing threshold difference between different hearing level groups and different age groups (P>0.05). There was a good correlation between adult CE-Chirp ABR V-wave response threshold and pure tone hearing threshold with statistical significance (P<0.05), and linear regression analysis showed a significant linear correlation between the two (P<0.05). CONCLUSIONS: The use of CE-Chirp ABR V-wave response threshold can be used to evaluate subjects' pure tone hearing threshold under certain conditions, and can be used as an audiological test method for forensic hearing impairment assessment.

A phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss.

Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change -0.87 dB; 95% CI -2.37 to 0.63; P = 0.252 and -0.46 dB; 95% CI -1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial's primary endpoint was not met.

Multisession anodal epidural direct current stimulation of the auditory cortex delays the progression of presbycusis in the Wistar rat.

Presbycusis or age-related hearing loss (ARHL) is one of the most prevalent chronic health problems facing aging populations. Along the auditory pathway, the stations involved in transmission and processing, function as a system of interconnected feedback loops. Regulating hierarchically auditory processing, auditory cortex (AC) neuromodulation can, accordingly, activate both peripheral and central plasticity after hearing loss. However, previous ARHL-prevention interventions have mainly focused on preserving the structural and functional integrity of the inner ear, overlooking the central auditory system. In this study, using an animal model of spontaneous ARHL, we aim at assessing the effects of multisession epidural direct current stimulation of the AC through stereotaxic implantation of a 1-mm silver ball anode in Wistar rats. Consisting of 7 sessions (0.1 mA/10 min), on alternate days, in awake animals, our stimulation protocol was applied at the onset of hearing loss (threshold shift detection at 16 months). Click- and pure-tone auditory brainstem responses (ABRs) were analyzed in two animal groups, namely electrically stimulated (ES) and non-stimulated (NES) sham controls, comparing recordings at 18 months of age. At 18 months, NES animals showed significantly increased threshold shifts, decreased wave amplitudes, and increased wave latencies after click and tonal ABRs, reflecting a significant, spontaneous ARHL evolution. Conversely, in ES animals, no significant differences were detected in any of these parameters when comparing 16 and 18 months ABRs, indicating a delay in ARHL progression. Electrode placement in the auditory cortex was accurate, and the stimulation did not cause significant damage, as shown by the limited presence of superficial reactive microglial cells after IBA1 immunostaining. In conclusion, multisession DC stimulation of the AC has a protective effect on auditory function, delaying the progression of presbycusis.

Auditory sensitivity and tympanic middle ear in a vocal and a non-vocal frog.

The tympanic middle ear is important for anuran hearing on land. However, many species have partly or entirely lost their tympanic apparatus. Previous studies have compared hearing sensitivities in species that possess and lack tympanic membranes capable of sound production and acoustic communication. However, little is known about how these hearing abilities are comparable to those of mutant species. Here, we compared the eardrum and middle ear anatomies of two sympatric sibling species from a noisy stream habitat, namely the "non-vocal" Hainan torrent frog (Amolops hainanensis) and the "vocal" little torrent frog (Amolops torrentis), the latter of which is capable of acoustic communication. Our results showed that the relative (to head size) eardrum diameter of A. hainanensis was smaller than that of A. torrentis, although the absolute size was not smaller. Unlike A. torrentis, the tympanic membrane area of A. hainanensis was not clearly differentiated from the surrounding skin. The middle ear, however, was well-developed in both species. We measured the auditory brainstem responses (ABRs) of A. hainanensis and compared the ABR thresholds and latencies to those previously obtained for A. torrentis. Our results suggested that these two species exhibited significant differences in hearing sensitivity. A. hainanensis (smaller relative eardrum, nonvocal) had higher ABR thresholds and longer initial response times than A. torrentis (larger relative eardrum, vocal) at lower frequencies. Neurophysiological responses from the brain were obtained for tone pips between 800 Hz and 7,000 Hz, with peak sensitivities found at 3,000 Hz (73 dB SPL) for A. hainanensis, and at 1,800 Hz (61 dB SPL) for A. torrentis. Our results suggest that the non-vocal A. hainanensis has lower hearing sensitivity than its vocal sister species (i.e., A. torrentis), which may be related to differences in tympanic or inner ear structure and morphology.

An eight-year follow-up on auditory outcomes after neonatal hearing screening.

OBJECTIVE: The aim of this study is to assess the neonatal click Auditory Brainstem Response (ABR) results in relation to the subsequently determined mean hearing loss (HL) over 1, 2 and 4 kHz, as well as over 2 and 4 kHz. METHODS: Between 2004-2009, follow-up data were collected from Visual Reinforcement Audiometry (VRA) at 1 and 2 years and playaudiometry at 4 and 8 years of newborns who had failed neonatal hearing screening in the well-baby clinics and who had been referred to a single Speech and Hearing center. Hearing Level data were compared with ABR threshold-levels established during the first months of life. The Two One-Sided Tests equivalence procedure for paired means was applied, using a region of similarity equal to 10 dB. RESULTS: Initially, in 135 out of 172 children referred for diagnostic procedures hearing loss was confirmed in the neonatal period. In 106/135 of the HL children the eight-year follow-up was completed. Permanent conductive HL was established in 5/106 cases; the hearing thresholds were predominantly stable over time. Temporary conductive HL was found in 48/106 cases and the loss disappeared by 4 years of age at the latest. Sensorineural hearing loss (SNHL) was found in 53/106 cases, of which 13 were unilateral and 40 bilateral. ABR levels were equivalent (within a 10 dB range) to VRA levels at age 1 and 2 and play audiometry levels at age 4 and 8, both when VRA and play audiometry were averaged over both frequency ranges. CONCLUSION: Long term follow-up data of children with SNHL suggest that the initial click ABR level established in the first months of life, are equivalent to the hearing threshold measured at the age of 1, 2, 4 and 8 years for both mean frequency ranges. Click ABR can reliably be used as starting point for long-term hearing rehabilitation.

Hidden hearing loss: Fifteen years at a glance.

Hearing loss affects approximately 18% of the population worldwide. Hearing difficulties in noisy environments without accompanying audiometric threshold shifts likely affect an even larger percentage of the global population. One of the potential causes of hidden hearing loss is cochlear synaptopathy, the loss of synapses between inner hair cells (IHC) and auditory nerve fibers (ANF). These synapses are the most vulnerable structures in the cochlea to noise exposure or aging. The loss of synapses causes auditory deafferentation, i.e., the loss of auditory afferent information, whose downstream effect is the loss of information that is sent to higher-order auditory processing stages. Understanding the physiological and perceptual effects of this early auditory deafferentation might inform interventions to prevent later, more severe hearing loss. In the past decade, a large body of work has been devoted to better understand hidden hearing loss, including the causes of hidden hearing loss, their corresponding impact on the auditory pathway, and the use of auditory physiological measures for clinical diagnosis of auditory deafferentation. This review synthesizes the findings from studies in humans and animals to answer some of the key questions in the field, and it points to gaps in knowledge that warrant more investigation. Specifically, recent studies suggest that some electrophysiological measures have the potential to function as indicators of hidden hearing loss in humans, but more research is needed for these measures to be included as part of a clinical test battery.

How 'hidden hearing loss' noise exposure affects neural coding in the inferior colliculus of rats.

Exposure to brief, intense sound can produce profound changes in the auditory system, from the internal structure of inner hair cells to reduced synaptic connections between the auditory nerves and the inner hair cells. Moreover, noisy environments can also lead to alterations in the auditory nerve or to processing changes in the auditory midbrain, all without affecting hearing thresholds. This so-called hidden hearing loss (HHL) has been shown in tinnitus patients and has been posited to account for hearing difficulties in noisy environments. However, much of the neuronal research thus far has investigated how HHL affects the response characteristics of individual fibres in the auditory nerve, as opposed to higher stations in the auditory pathway. Human models show that the auditory nerve encodes sound stochastically. Therefore, a sufficient reduction in nerve fibres could result in lowering the sampling of the acoustic scene below the minimum rate necessary to fully encode the scene, thus reducing the efficacy of sound encoding. Here, we examine how HHL affects the responses to frequency and intensity of neurons in the inferior colliculus of rats, and the duration and firing rate of those responses. Finally, we examined how shorter stimuli are encoded less effectively by the auditory midbrain than longer stimuli, and how this could lead to a clinical test for HHL.

[Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/- mice].

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.

Effect of Stimulus Bandwidth on the Auditory Steady-State Response in Scalp- and Ear-EEG.

OBJECTIVES: The auditory steady-state response (ASSR) enables hearing threshold estimation based on electroencephalography (EEG) recordings. The choice of stimulus type has an impact on both the detectability and the frequency specificity of the ASSR. Amplitude modulated pure tones provide the most frequency-specific ASSR, but responses to pure tones are weak. The ASSR can be enhanced by increasing the bandwidth of the stimulus, but this comes at the cost of a decrease in the frequency specificity of the measured response. The objective of the present study is to investigate the relationship between stimulus bandwidth and ASSR amplitude. DESIGN: The amplitude of ASSR was measured for five types of stimuli: 1 kHz pure tone and band-pass noise with 1/3, 1/2, 1, and 2 octave bandwidths centered at 1 kHz. All stimuli were amplitude modulated with a 40 Hz sinusoid. Responses to all stimulus types were measured at 30, 40, and 50 dB SL. ASSRs were measured concurrently using both conventional scalp-EEG and ear-EEG. RESULTS: Stimulus bandwidth and sound intensity were both found to have a significant effect on the ASSR amplitude for scalp- and ear-EEG recordings. In scalp-EEG ASSRs to all bandwidth stimuli were found to be significantly larger than ASSRs to pure tone at low sound intensity. At higher sound intensities, however, significantly larger responses were only obtained for 1- and 2-octave bandwidth stimuli. In ear-EEG, only the ASSR to 2 octave bandwidth stimulus was significantly larger than the ASSR to amplitude modulated pure tones. CONCLUSIONS: At low presentation levels, even small increases in stimulus bandwidth (1/3 and 1/2 octave) improve the detectability of ASSR in scalp-EEG with little or no impact on the frequency specificity. In comparison, a larger increase in stimulus bandwidth was needed to improve the ASSR detectability in the ear-EEG recordings.

Quantifying the Impact of Auditory Deafferentation on Speech Perception.

The past decade has seen a wealth of research dedicated to determining which and how morphological changes in the auditory periphery contribute to people experiencing hearing difficulties in noise despite having clinically normal audiometric thresholds in quiet. Evidence from animal studies suggests that cochlear synaptopathy in the inner ear might lead to auditory nerve deafferentation, resulting in impoverished signal transmission to the brain. Here, we quantify the likely perceptual consequences of auditory deafferentation in humans via a physiologically inspired encoding-decoding model. The encoding stage simulates the processing of an acoustic input stimulus (e.g., speech) at the auditory periphery, while the decoding stage is trained to optimally regenerate the input stimulus from the simulated auditory nerve firing data. This allowed us to quantify the effect of different degrees of auditory deafferentation by measuring the extent to which the decoded signal supported the identification of speech in quiet and in noise. In a series of experiments, speech perception thresholds in quiet and in noise increased (worsened) significantly as a function of the degree of auditory deafferentation for modeled deafferentation greater than 90%. Importantly, this effect was significantly stronger in a noisy than in a quiet background. The encoding-decoding model thus captured the hallmark symptom of degraded speech perception in noise together with normal speech perception in quiet. As such, the model might function as a quantitative guide to evaluating the degree of auditory deafferentation in human listeners.

A Multicenter Validity Study of Four Smartphone Hearing Test Apps in Optimized and Home Environments.

OBJECTIVE: Pure tone audiometry (PTA) is the gold standard for hearing assessment. However, it requires access to specialized equipment. Smartphone audiometry applications (apps) have been developed to perform automated threshold audiometry and could allow patients to perform self-administered screening or monitoring. This study aimed to assess the validity and feasibility of patients using apps to self-assess hearing thresholds at home, with comparison to PTA. METHODS: A multi-center, prospective randomized study was conducted amongst patients undergoing PTA in clinics. Participants were randomly allocated to one of four publicly-available apps designed to measure pure tone thresholds. Participants used an app once in optimal sound-treated conditions and a further three times at home. Ear-specific frequency-specific thresholds and pure tone average were compared using Pearson correlation coefficient. The percentage of app hearing tests with results within ±10 dB of PTA was calculated. Patient acceptability was assessed via an online survey. RESULTS: One hundred thirty-nine participants submitted data. The results of two at-home automated smartphone apps correlated strongly/very strongly with PTA average and their frequency-specific median was within ±10 dB accuracy. Smartphone audiometry performed in sound-treated and home conditions were very strongly correlated. The apps were rated as easy/very easy to use by 90% of participants and 90% would be happy/very happy to use an app to monitor their hearing. CONCLUSION: Judicious use of self-performed smartphone audiometry was both valid and feasible for two of four apps. It could provide frequency-specific threshold estimates at home, potentially allowing assessments of patients remotely or monitoring of fluctuating hearing loss. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:2864-2870, 2024.