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?

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.

Audiologic Outcomes After Vestibulotomy in Patients With Congenital Absence of the Oval Window.

OBJECTIVE: To examine the clinical features and surgical outcomes in patients with congenital absence of the oval window (CAOW), and to investigate the potential factors that affect audiologic results. STUDY DESIGN: A retrospective chart review. SETTING: A tertiary academic center. PATIENTS AND INTERVENTION: A total of 17 ears among 16 patients were confirmed to have CAOW. Among them, 13 ears underwent vestibulotomy for hearing reconstruction. Clinical parameters associated with the hearing outcomes were analyzed. MAIN OUTCOME MEASURES: A mean air-bone gap (ABG) after 6-month and long-term follow-up was compared with preoperative measurements. RESULTS: Intraoperative findings showed that anomalies of the malleus or incus were observed in 11 ears (64.7%), stapes anomalies were present in all ears (100%), and facial nerve anomalies were present in 10 ears (58.8%). Because of unfavorable facial nerve anomalies, hearing reconstruction was aborted in four cases (23.5%). In the hearing reconstruction group, the mean ABG at 6 months postoperation was significantly reduced after compared with the preoperative value (44.0 ± 8.4 dB versus 58.8 ± 9.1 dB, p = 0.006). After dividing ears into a success subgroup (ABG ≤ 30 dB, seven ears) and non-success subgroup (ABG > 30 dB, six ears), the use of a drill during vestibulotomy was significantly related to a poor hearing outcome (100% versus 16.7%, p = 0.015). The long-term follow-up result (mean, 60 mo) revealed no deterioration compared with the 6-month postoperative result. Five ears (29.4%) underwent revision surgery, and three of them showed ABG improvements. No serious complications were reported. CONCLUSION: Vestibulotomy is an effective and safe option for hearing restoration in patients with CAOW, particularly when the use of a drill is not required. The long-term audiologic outcome is also reliable.

Auditory neuroscience: Sounds make the face move.

Animals including humans often react to sounds by involuntarily moving their face and body. A new study shows that facial movements provide a simple and reliable readout of a mouse's hearing ability that is more sensitive than traditional measurements.

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.

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.

The impact of size on middle-ear sound transmission in elephants, the largest terrestrial mammal.

Elephants have a unique auditory system that is larger than any other terrestrial mammal. To quantify the impact of larger middle ear (ME) structures, we measured 3D ossicular motion and ME sound transmission in cadaveric temporal bones from both African and Asian elephants in response to air-conducted (AC) tonal pressure stimuli presented in the ear canal (PEC). Results were compared to similar measurements in humans. Velocities of the umbo (VU) and stapes (VST) were measured using a 3D laser Doppler vibrometer in the 7-13,000 Hz frequency range, stapes velocity serving as a measure of energy entering the cochlea-a proxy for hearing sensitivity. Below the elephant ME resonance frequency of about 300 Hz, the magnitude of VU/PEC was an order of magnitude greater than in human, and the magnitude of VST/PEC was 5x greater. Phase of VST/PEC above ME resonance indicated that the group delay in elephant was approximately double that of human, which may be related to the unexpectedly high magnitudes at high frequencies. A boost in sound transmission across the incus long process and stapes near 9 kHz was also observed. We discuss factors that contribute to differences in sound transmission between these two large mammals.

Used to Be a Dime, Now It's a Dollar: Revised Speech Perception in Noise Key Word Predictability Revisited 40 Years On.

PURPOSE: Almost 40 years after its development, in this article, we reexamine the relevance and validity of the ubiquitously used Revised Speech Perception in Noise (R-SPiN) sentence corpus. The R-SPiN corpus includes "high-context" and "low-context" sentences and has been widely used in the field of hearing research to examine the benefit derived from semantic context across English-speaking listeners, but research investigating age differences has yielded somewhat inconsistent findings. We assess the appropriateness of the corpus for use today in different English-language cultures (i.e., British and American) as well as for older and younger adults. METHOD: Two hundred forty participants, including older (60-80 years) and younger (19-31 years) adult groups in the the United Kingdom and United States, completed a cloze task consisting of R-SPiN sentences with the final word removed. Cloze, as a measure of predictability, and entropy, as a measure of response uncertainty, were compared between culture and age groups. RESULTS: Most critically, of the 200 "high-context" stimuli, only around half were assessed as highly predictable for older adults (United Kingdom: 109; United States: 107); and fewer still, for younger adults (United Kingdom: 75; United States: 81). We also found dominant responses to these "high-context" stimuli varied between cultures, with U.S. responses being more likely to match the original R-SPiN target. CONCLUSIONS: Our findings highlight the issue of incomplete transferability of corpus items across English-language cultures as well as diminished equivalency for older and younger adults. By identifying relevant items for each population, this work could facilitate the interpretation of inconsistent findings in the literature, particularly relating to age effects.

[A study of mismatched negative in normal hearing patients of different ages].

Objective:To study the characteristics of Mismatch negativity（MMN） in normal hearing patients of different ages, and to compare the MMN of normal hearing subjects at different ages to explore the differences in MMN between different ages. Methods:MMN test was performed on both ears using the classic Oddball mode. A frequency of 1 000 Hz（standard stimuli） and 2 000 Hz（deviant stimuli） was used to evoked the MMN. According to different age groups: the juvenile group（7-17 years old）, the youth group（18-44 years old）, the middle-aged group（45-59 years old）, and the elderly group（60-75 years old）, with 25 cases in each group. The MMN characteristics of normal hearing subjects in different age groups were analyzed statistically and the differences between groups were compared. All subjects underwent pure tone threshold test, tympanic reactance test and ABR test before MMN test. Results:MMN waveform could be elicited from both ears of 100 subjects. Among them, the average latency of the juvenile group was（159.70±20.34） ms while the average amplitude was（4.34±2.26） µV, For the youth group, the average latency was（166.01±28.67） ms and the average amplitude was（3.70±2.28） µV. Then in the middle-aged group, the average latency was（175.16±37.24） ms, meanwhile, the average amplitude was（2.69±0.84） µV. Finally, the elderly group has an average latency of（178.03±14.37） ms and an average amplitude of（2.11±0.70） µV. Therefore, there was no statistical difference in latency and amplitude between all groups（P>0.05）, and there was no statistical difference in latency and amplitude between left and right ears among all subjects as a whole（P>0.05）. However, when the left and right ears of all groups were compared, it was found that the latency between the left and right ears of the Juvenile group had statistical significance（P<0.05）, and the amplitude difference was not statistically significant（P>0.05）, while the latency and amplitude differences between the left and right ears of other groups had no statistical significance（P>0.05）. There were also no significant differences in latency and amplitude between men and women（P>0.05）. Conclusion:There was no statistically significant difference in the latency and amplitude of mismatched negative among normal hearing subjects of different ages, and no statistically significant difference in the MMN latency and amplitude between the left and right ears of subjects and between men and women. Therefore, the study inferred that the auditory cerebral cortex of subjects aged 7-75 years old maintained a stable state for a long time after maturity, and the latency and amplitude of mismatched negative waves were relatively stable. It is not affected by age, gender and ear side, and can stably reflect the auditory cortex function of the subjects. It has broad application prospects in clinical practice, and provides a reliable detection means for future research on the changes of the auditory cerebral cortex of patients, which is worthy of our further research and clinical promotion.

BAI1 localizes AMPA receptors at the cochlear afferent post-synaptic density and is essential for hearing.

Type I spiral ganglion neurons (SGNs) convey sound information to the central auditory pathway by forming synapses with inner hair cells (IHCs) in the mammalian cochlea. The molecular mechanisms regulating the formation of the post-synaptic density (PSD) in the SGN afferent terminals are still unclear. Here, we demonstrate that brain-specific angiogenesis inhibitor 1 (BAI1) is required for the clustering of AMPA receptors GluR2-4 (glutamate receptors 2-4) at the PSD. Adult Bai1-deficient mice have functional IHCs but fail to transmit information to the SGNs, leading to highly raised hearing thresholds. Despite the almost complete absence of AMPA receptor subunits, the SGN fibers innervating the IHCs do not degenerate. Furthermore, we show that AMPA receptors are still expressed in the cochlea of Bai1-deficient mice, highlighting a role for BAI1 in trafficking or anchoring GluR2-4 to the PSDs. These findings identify molecular and functional mechanisms required for sound encoding at cochlear ribbon synapses.

Otic Capsule Demineralization and Hearing Outcome of Stapes Surgery for Osteogenesis Imperfecta in Comparison With Otosclerosis.

OBJECTIVE: To assess the location/number of otic capsule demineralization and hearing outcomes of stapes surgery (SS) for osteogenesis imperfecta (OI) compared with otosclerosis (OS). PATIENTS: This study included 11 and 181 consecutive ears from 6 and 152 patients with OI and OS, respectively. INTERVENTIONS: Demineralization loci observed as hypodense area of the otic capsule were examined using high-resolution computed tomography. All patients underwent SS. MAIN OUTCOME MEASURES: Locations of the hypodense areas were classified into the anterior oval window, anterior internal auditory canal, and pericochlear area. The location/number of hypodense areas and preoperative/postoperative hearing parameters were correlated. Postoperative hearing outcome was evaluated 12 months after surgery. RESULTS: Hypodense area was more frequently observed in OI (9 of 11 ears [81.8%]) than in OS (96 of 181 ears [53.0%]), with significant differences. Multiple sites were involved in 81.8% OI and 18.8% OS patients, showing significant differences. Preoperative air conduction (AC), bone conduction, and air-bone gap (ABG) were 48.9 ± 17.8, 28.0 ± 11.3, and 20.7 ± 8.4 dB, respectively, in OI and 56.2 ± 13.5, 30.5 ± 9.9, and 26.4 ± 9.7 dB, respectively, in OS, demonstrating greater AC and ABG in OS than in OI. Postoperative AC (31.3 ± 20.5 dB), ABG (10.6 ± 10.0 dB), and closure of ABG (12.1 ± 4.7 dB), that is, preoperative ABG minus postoperative ABG of OI, were comparable to those of OS (AC, 30.9 ± 13.3 dB; ABG, 7.0 ± 7.4 dB; closure of ABG, 20.1 ± 11.6 dB). CONCLUSION: OI ears showed more severe demineralization of otic capsule than OS ears. However, favorable hearing outcomes could be obtained through SS for OI and OS ears.

Sound elicits stereotyped facial movements that provide a sensitive index of hearing abilities in mice.

Sound elicits rapid movements of muscles in the face, ears, and eyes that protect the body from injury and trigger brain-wide internal state changes. Here, we performed quantitative facial videography from mice resting atop a piezoelectric force plate and observed that broadband sounds elicited rapid and stereotyped facial twitches. Facial motion energy (FME) adjacent to the whisker array was 30 dB more sensitive than the acoustic startle reflex and offered greater inter-trial and inter-animal reliability than sound-evoked pupil dilations or movement of other facial and body regions. FME tracked the low-frequency envelope of broadband sounds, providing a means to study behavioral discrimination of complex auditory stimuli, such as speech phonemes in noise. Approximately 25% of layer 5-6 units in the auditory cortex (ACtx) exhibited firing rate changes during facial movements. However, FME facilitation during ACtx photoinhibition indicated that sound-evoked facial movements were mediated by a midbrain pathway and modulated by descending corticofugal input. FME and auditory brainstem response (ABR) thresholds were closely aligned after noise-induced sensorineural hearing loss, yet FME growth slopes were disproportionately steep at spared frequencies, reflecting a central plasticity that matched commensurate changes in ABR wave 4. Sound-evoked facial movements were also hypersensitive in Ptchd1 knockout mice, highlighting the use of FME for identifying sensory hyper-reactivity phenotypes after adult-onset hyperacusis and inherited deficiencies in autism risk genes. These findings present a sensitive and integrative measure of hearing while also highlighting that even low-intensity broadband sounds can elicit a complex mixture of auditory, motor, and reafferent somatosensory neural activity.

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.

Thyroid hormone controls the timing of cochlear ribbon synapse maturation.

Ribbon synapses in the cochlear hair cells are subject to extensive pruning and maturation processes before hearing onset. Previous studies have highlighted the pivotal role of thyroid hormone (TH) in this developmental process, yet the detailed mechanisms are largely unknown. In this study, we found that the thyroid hormone receptor α (Thrα) is expressed in both sensory epithelium and spiral ganglion neurons in mice. Hypothyroidism, induced by Pax8 gene knockout, significantly delays the synaptic pruning during postnatal development in mice. Detailed spatiotemporal analysis of ribbon synapse distribution reveals that synaptic maturation involves not only ribbon pruning but also their migration, both of which are notably delayed in the cochlea of Pax8 knockout mice. Intriguingly, postnatal hyperthyroidism, induced by intraperitoneal injections of liothyronine sodium (T3), accelerates the pruning of ribbon synapses to the mature state without affecting the auditory functions. Our findings suggest that thyroid hormone does not play a deterministic role but rather controls the timing of cochlear ribbon synapse maturation.

Newborn Hearing Screening Results for Infants With Prenatal Opioid Exposure in Southern Appalachia.

PURPOSE: Infants prenatally exposed to opioids exhibit withdrawal symptomology that introduce physiological noise and can impact newborn hearing screening results. This study compared the referral rate and physiological noise interpreted by number of trials rejected due to artifact on initial newborn hearing screenings of infants with prenatal opioid exposure (POE) and infants with no opioid exposure (NOE). Furthermore, within the POE group, it examined the relationship of referral rates with severity of withdrawal symptomology, and with maternal and infant risk factors. METHOD: This study used a retrospective cohort design of electronic medical records from six delivery hospitals in South-Central Appalachia. Newborn hearing screenings were conducted using automated auditory brainstem response (ABR) for 334 infants with POE and 226 infants with NOE. Severity of withdrawal symptomology was measured using the Modified Finnegan Neonatal Abstinence Scoring Tool, which includes observation of behaviors that introduce physiological noise. RESULTS: There was no significant difference in newborn hearing screening referral rate between infants with POE and infants with NOE. Referral rate was not affected by maternal or infant risk factors. Infants with POE had statistically significant higher artifact (defined as rejected ABR sweeps) than infants with NOE. There was a strong positive correlation between Finnegan scores and artifact but not referral rates. Sensitivity and specificity analysis indicated artifact decreased substantially after Day 4 of life. CONCLUSIONS: Referral rates of infants with POE were similar to those of infants with NOE. Nevertheless, the withdrawal symptomology of infants with POE introduces physiological noise reflected as artifact on ABR, which can affect efficiency of newborn hearing screenings.

Recent advances in Otology: Current landscape and future direction.

Hearing is an essential sensation, and its deterioration leads to a significant decrease in the quality of life. Thus, great efforts have been made by otologists to preserve and recover hearing. Our knowledge regarding the field of otology has progressed with advances in technology, and otologists have sought to develop novel approaches in the field of otologic surgery to achieve higher hearing recovery or preservation rates. This requires knowledge regarding the anatomy of the temporal bone and the physiology of hearing. Basic research in the field of otology has progressed with advances in molecular biology and genetics. This review summarizes the current views and recent advances in the field of otology and otologic surgery, especially from the viewpoint of young Japanese clinician-scientists, and presents the perspectives and future directions for several topics in the field of otology. This review will aid next-generation researchers in understanding the recent advances and future challenges in the field of otology.

Age-Related Deficits in Binaural Hearing: Contribution of Peripheral and Central Effects.

Pure-tone audiograms often poorly predict elderly humans' ability to communicate in everyday complex acoustic scenes. Binaural processing is crucial for discriminating sound sources in such complex acoustic scenes. The compromised perception of communication signals presented above hearing threshold has been linked to both peripheral and central age-related changes in the auditory system. Investigating young and old Mongolian gerbils of both sexes, an established model for human hearing, we demonstrate age-related supra-threshold deficits in binaural hearing using behavioral, electrophysiological, anatomical, and imaging methods. Binaural processing ability was measured as the binaural masking level difference (BMLD), an established measure in human psychophysics. We tested gerbils behaviorally with "virtual headphones," recorded single-unit responses in the auditory midbrain and evaluated gross midbrain and cortical responses using positron emission tomography (PET) imaging. Furthermore, we obtained additional measures of auditory function based on auditory brainstem responses, auditory-nerve synapse counts, and evidence for central inhibitory processing revealed by PET. BMLD deteriorates already in middle-aged animals having normal audiometric thresholds and is even worse in old animals with hearing loss. The magnitude of auditory brainstem response measures related to auditory-nerve function and binaural processing in the auditory brainstem also deteriorate. Furthermore, central GABAergic inhibition is affected by age. Because the number of synapses in the apical turn of the inner ear was not reduced in middle-aged animals, we conclude that peripheral synaptopathy contributes little to binaural processing deficits. Exploratory analyses suggest increased hearing thresholds, altered binaural processing in the brainstem and changed central GABAergic inhibition as potential contributors.

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.

Predictors for estimating subcortical EEG responses to continuous speech.

Perception of sounds and speech involves structures in the auditory brainstem that rapidly process ongoing auditory stimuli. The role of these structures in speech processing can be investigated by measuring their electrical activity using scalp-mounted electrodes. However, typical analysis methods involve averaging neural responses to many short repetitive stimuli that bear little relevance to daily listening environments. Recently, subcortical responses to more ecologically relevant continuous speech were detected using linear encoding models. These methods estimate the temporal response function (TRF), which is a regression model that minimises the error between the measured neural signal and a predictor derived from the stimulus. Using predictors that model the highly non-linear peripheral auditory system may improve linear TRF estimation accuracy and peak detection. Here, we compare predictors from both simple and complex peripheral auditory models for estimating brainstem TRFs on electroencephalography (EEG) data from 24 participants listening to continuous speech. We also investigate the data length required for estimating subcortical TRFs, and find that around 12 minutes of data is sufficient for clear wave V peaks (>3 dB SNR) to be seen in nearly all participants. Interestingly, predictors derived from simple filterbank-based models of the peripheral auditory system yield TRF wave V peak SNRs that are not significantly different from those estimated using a complex model of the auditory nerve, provided that the nonlinear effects of adaptation in the auditory system are appropriately modelled. Crucially, computing predictors from these simpler models is more than 50 times faster compared to the complex model. This work paves the way for efficient modelling and detection of subcortical processing of continuous speech, which may lead to improved diagnosis metrics for hearing impairment and assistive hearing technology.

[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.