Single-unit data for sensory neuroscience: Responses from the auditory nerve of young-adult and aging gerbils.

This dataset was collected to study the functional consequences of age-related hearing loss for the auditory nerve, which carries acoustic information from the periphery to the central auditory system. Using high-impedance glass electrodes, raw voltage traces and spike times were recorded from more than one thousand single fibres of the auditory nerve of young-adult, middle-aged, and old Mongolian gerbils raised in a quiet environment. The dataset contains not only responses to simple acoustic stimuli to characterize the fibres, but also to more complex stimuli, such as speech logatomes in background noise and Schroeder-phase stimuli. A software toolbox is provided to search through the dataset, to plot various analysed outcomes, and to give insight into the analyses. This dataset may serve as a valuable resource to test further hypotheses about age-related hearing loss. Additionally, it can aid in optimizing available computational models of the auditory system, which can contribute to, or eventually even fully replace, animal experiments.

Predicting early auditory evoked potentials using a computational model of auditory-nerve processing.

Non-invasive electrophysiological measures, such as auditory evoked potentials (AEPs), play a crucial role in diagnosing auditory pathology. However, the relationship between AEP morphology and cochlear degeneration remains complex and not well understood. Dau [J. Acoust. Soc. Am. 113, 936-950 (2003)] proposed a computational framework for modeling AEPs that utilized a nonlinear auditory-nerve (AN) model followed by a linear unitary response function. While the model captured some important features of the measured AEPs, it also exhibited several discrepancies in response patterns compared to the actual measurements. In this study, an enhanced AEP modeling framework is presented, incorporating an improved AN model, and the conclusions from the original study were reevaluated. Simulation results with transient and sustained stimuli demonstrated accurate auditory brainstem responses (ABRs) and frequency-following responses (FFRs) as a function of stimulation level, although wave-V latencies remained too short, similar to the original study. When compared to physiological responses in animals, the revised model framework showed a more accurate balance between the contributions of auditory-nerve fibers (ANFs) at on- and off-frequency regions to the predicted FFRs. These findings emphasize the importance of cochlear processing in brainstem potentials. This framework may provide a valuable tool for assessing human AN models and simulating AEPs for various subtypes of peripheral pathologies, offering opportunities for research and clinical applications.

A frequency peak at 3.1 kHz obtained from the spectral analysis of the cochlear implant electrocochleography noise.

INTRODUCTION: The functional evaluation of auditory-nerve activity in spontaneous conditions has remained elusive in humans. In animals, the frequency analysis of the round-window electrical noise recorded by means of electrocochleography yields a frequency peak at around 900 to 1000 Hz, which has been proposed to reflect auditory-nerve spontaneous activity. Here, we studied the spectral components of the electrical noise obtained from cochlear implant electrocochleography in humans. METHODS: We recruited adult cochlear implant recipients from the Clinical Hospital of the Universidad de Chile, between the years 2021 and 2022. We used the AIM System from Advanced Bionics® to obtain single trial electrocochleography signals from the most apical electrode in cochlear implant users. We performed a protocol to study spontaneous activity and auditory responses to 0.5 and 2 kHz tones. RESULTS: Twenty subjects including 12 females, with a mean age of 57.9 ± 12.6 years (range between 36 and 78 years) were recruited. The electrical noise of the single trial cochlear implant electrocochleography signal yielded a reliable peak at 3.1 kHz in 55% of the cases (11 out of 20 subjects), while an oscillatory pattern that masked the spectrum was observed in seven cases. In the other two cases, the single-trial noise was not classifiable. Auditory stimulation at 0.5 kHz and 2.0 kHz did not change the amplitude of the 3.1 kHz frequency peak. CONCLUSION: We found two main types of noise patterns in the frequency analysis of the single-trial noise from cochlear implant electrocochleography, including a peak at 3.1 kHz that might reflect auditory-nerve spontaneous activity, while the oscillatory pattern probably corresponds to an artifact.

Evolution of air-borne vocalization: Insights from neural studies in the archeobatrachian species Bombina orientalis.

Vocalization of tetrapods evolved as an air-driven mechanism. Thus, it is conceivable that the underlaying neural network might have evolved from more ancient respiratory circuits and be made up of homologous components that generate breathing rhythms across vertebrates. In this context, the extant species of stem anurans provide an opportunity to analyze the connection of the neural circuits of lung ventilation and vocalization. Here, we analyzed the fictive lung ventilation and vocalization behavior of isolated brains of the Chinese fire-bellied toad Bombina orientalis during their mating season by nerve root recordings. We discovered significant differences in durations of activation of male brains after stimulation of the statoacoustic nerve or vocalization-relevant forebrain structures in comparison to female brains. The increased durations of motor nerve activities in male brains can be interpreted as fictive calling, as male's advertisement calls in vivo had the same general pattern compared to lung ventilation, but longer duration periods. Female brains react to the corresponding stimulations with the same shorter activity pattern that occurred spontaneously in both female and male brains and thus can be interpreted as fictive lung ventilations. These results support the hypothesis that vocal circuits evolved from ancient respiration networks in the anuran caudal hindbrain. Moreover, we could show that the terrestrial stem archeobatrachian Bombina spec. is an appropriate model to study the function and evolution of the shared network of lung ventilation and vocal generation.

Cochlear Ribbon Synapses in Aged Gerbils.

In mammalian hearing, type-I afferent auditory nerve fibers comprise the basis of the afferent auditory pathway. They are connected to inner hair cells of the cochlea via specialized ribbon synapses. Auditory nerve fibers of different physiological types differ subtly in their synaptic location and morphology. Low-spontaneous-rate auditory nerve fibers typically connect on the modiolar side of the inner hair cell, while high-spontaneous-rate fibers are typically found on the pillar side. In aging and noise-damaged ears, this fine-tuned balance between auditory nerve fiber populations can be disrupted and the functional consequences are currently unclear. Here, using immunofluorescent labeling of presynaptic ribbons and postsynaptic glutamate receptor patches, we investigated changes in synaptic morphology at three different tonotopic locations along the cochlea of aging gerbils compared to those of young adults. Quiet-aged gerbils showed about 20% loss of afferent ribbon synapses. While the loss was random at apical, low-frequency cochlear locations, at the basal, high-frequency location it almost exclusively affected the modiolar-located synapses. The subtle differences in volumes of pre- and postsynaptic elements located on the inner hair cell's modiolar versus pillar side were unaffected by age. This is consistent with known physiology and suggests a predominant, age-related loss in the low-spontaneous-rate auditory nerve population in the cochlear base, but not the apex.

Comparing pronunciation challenges in South Korean preschoolers with unilateral single-sided deafness due to cochlear nerve deficiency to a norm-referenced standard.

This study aimed to compare the development of pronunciation in South Korean preschoolers with unilateral cochlear nerve deficiency (CND) to that of age-matched preschoolers with normal hearing, a topic that has not been explored previously. In a retrospective analysis, 25 preschoolers with unilateral CND who had undergone a speech evaluation battery, including a pronunciation and vocabulary test, were enrolled. Utilizing the Urimal Test of Articulation and Phonation and customized language ability tests, pronunciation and vocabulary were assessed. The subjects' speech evaluation scores were converted into age-adjusted z-scores using normal controls' data. While vocabulary performance was within normal limits, their average pronunciation z-score was -2.90, significantly lower than both the zero reference point and their vocabulary z-scores. None of the subjects scored above average in pronunciation. Thirteen patients were recommended for articulation therapy, seven were considered as potential candidates for this therapy, and the remaining five were within normal limits. There was no observed correlation between the development of pronunciation and vocabulary. Notably, some subjects' pronunciation scores did not improve, even after serial follow-up during their preschool years. Despite typical vocabulary development, preschoolers with unilateral CND exhibit significant delays in pronunciation. These findings emphasize the necessity for vigilant monitoring of their language development.

Comparison of Two Measurement Paradigms to Determine Electrically Evoked Cochlear Nerve Responses and Their Correlation to Cochlear Nerve Cross-section in Infants and Young Children With Cochlear Implant.

INTRODUCTION: Electrically evoked compound action potentials (ECAPs) are used for intra-/postoperative monitoring with intracochlear stimulation of cochlear implants. ECAPs are recorded in MED-EL (Innsbruck, Austria) implants using auditory response telemetry (ART), which has been further developed with automatic threshold determination as AutoART. The success of an ECAP measurement also depends on the number of available spiral ganglion cells and the bipolar neurons of the cochlear nerve (CN). It is assumed that a higher population of spiral ganglion cell implies a larger CN cross-sectional area (CSA), which consequently affects ECAP measurements. METHODS: Intraoperative ECAP measurements from 19 implanted ears of children aged 8 to 18 months were retrospectively evaluated. A comparison and correlation of ART/AutoART ECAP thresholds/slopes at electrodes E2 (apical), E6 (medial), E10 (basal), and averaged E1 to E12 with CN CSA on magnetic resonance imaging was performed. RESULTS: A Pearson correlation of the ART/AutoART ECAP thresholds/slopes for E2/E6/E10 and the averaged electrodes E1 to E12 showed a significant correlation. The CN CSA did not correlate significantly with the averaged ART/AutoART ECAP thresholds/slopes across all 12 electrodes. SUMMARY: AutoART provides reliable measurements and is therefore a suitable alternative to ART. No significant influence of CN CSA on ECAP thresholds/slopes was observed. A predictive evaluation of the success of ECAP measurements based on CN CSA for a clinical setting cannot be made according to the present data.

Neural Fluctuation Contrast as a Code for Complex Sounds: The Role and Control of Peripheral Nonlinearities.

The nonlinearities of the inner ear are often considered to be obstacles that the central nervous system has to overcome to decode neural responses to sounds. This review describes how peripheral nonlinearities, such as saturation of the inner-hair-cell response and of the IHC-auditory-nerve synapse, are instead beneficial to the neural encoding of complex sounds such as speech. These nonlinearities set up contrast in the depth of neural-fluctuations in auditory-nerve responses along the tonotopic axis, referred to here as neural fluctuation contrast (NFC). Physiological support for the NFC coding hypothesis is reviewed, and predictions of several psychophysical phenomena, including masked detection and speech intelligibility, are presented. Lastly, a framework based on the NFC code for understanding how the medial olivocochlear (MOC) efferent system contributes to the coding of complex sounds is presented. By modulating cochlear gain control in response to both sound energy and fluctuations in neural responses, the MOC system is hypothesized to function not as a simple feedback gain-control device, but rather as a mechanism for enhancing NFC along the tonotopic axis, enabling robust encoding of complex sounds across a wide range of sound levels and in the presence of background noise. Effects of sensorineural hearing loss on the NFC code and on the MOC feedback system are presented and discussed.

Estimation of Cochlear Frequency Selectivity Using a Convolution Model of Forward-Masked Compound Action Potentials.

PURPOSE: Frequency selectivity is a fundamental property of the peripheral auditory system; however, the invasiveness of auditory nerve (AN) experiments limits its study in the human ear. Compound action potentials (CAPs) associated with forward masking have been suggested as an alternative to assess cochlear frequency selectivity. Previous methods relied on an empirical comparison of AN and CAP tuning curves in animal models, arguably not taking full advantage of the information contained in forward-masked CAP waveforms. METHODS: To improve the estimation of cochlear frequency selectivity based on the CAP, we introduce a convolution model to fit forward-masked CAP waveforms. The model generates masking patterns that, when convolved with a unitary response, can predict the masking of the CAP waveform induced by Gaussian noise maskers. Model parameters, including those characterizing frequency selectivity, are fine-tuned by minimizing waveform prediction errors across numerous masking conditions, yielding robust estimates. RESULTS: The method was applied to click-evoked CAPs at the round window of anesthetized chinchillas using notched-noise maskers with various notch widths and attenuations. The estimated quality factor Q10 as a function of center frequency is shown to closely match the average quality factor obtained from AN fiber tuning curves, without the need for an empirical correction factor. CONCLUSION: This study establishes a moderately invasive method for estimating cochlear frequency selectivity with potential applicability to other animal species or humans. Beyond the estimation of frequency selectivity, the proposed model proved to be remarkably accurate in fitting forward-masked CAP responses and could be extended to study more complex aspects of cochlear signal processing (e.g., compressive nonlinearities).

Insights Into Electrophysiological Metrics of Cochlear Health in Cochlear Implant Users Using a Computational Model.

PURPOSE: The hearing outcomes of cochlear implant users depend on the functional status of the electrode-neuron interface inside the cochlea. This can be assessed by measuring electrically evoked compound action potentials (eCAPs). Variations in cochlear neural health and survival are reflected in eCAP-based metrics. The difficulty in translating promising results from animal studies into clinical use has raised questions about to what degree eCAP-based metrics are influenced by non-neural factors. Here, we addressed these questions using a computational model. METHODS: A 2-D computational model was designed to simulate how electrical signals from the stimulating electrode reach the auditory nerve fibers distributed along the cochlea, evoking action potentials that can be recorded as compound responses at the recording electrodes. Effects of physiologically relevant variations in neural survival and in electrode-neuron and stimulating-recording electrode distances on eCAP amplitude growth functions (AGFs) were investigated. RESULTS: In line with existing literature, the predicted eCAP AGF slopes and the inter-phase gap (IPG) effects depended on the neural survival, but only when the IPG effect was calculated as the difference between the slopes of the two AGFs expressed in linear input-output scale. As expected, shallower eCAP AGF slopes were obtained for increased stimulating-recording electrode distance and larger eCAP thresholds for greater electrode-neuron distance. These non-neural factors had also minor interference on the predicted IPG effect. CONCLUSIONS: The model predictions demonstrate previously found dependencies of eCAP metrics on neural survival and non-neural aspects. The present findings confirm data from animal studies and provide insights into applying described metrics in clinical practice.

Frequency selectivity in monkey auditory nerve studied with suprathreshold multicomponent stimuli.

Data from non-human primates can help extend observations from non-primate species to humans. Here we report measurements on the auditory nerve of macaque monkeys in the context of a controversial topic important to human hearing. A range of techniques have been used to examine the claim, which is not generally accepted, that human frequency tuning is sharper than traditionally thought, and sharper than in commonly used animal models. Data from single auditory-nerve fibers occupy a pivotal position to examine this claim, but are not available for humans. A previous study reported sharper tuning in auditory-nerve fibers of macaque relative to the cat. A limitation of these and other single-fiber data is that frequency selectivity was measured with tonal threshold-tuning curves, which do not directly assess spectral filtering and whose shape is sharpened by cochlear nonlinearity. Our aim was to measure spectral filtering with wideband suprathreshold stimuli in the macaque auditory nerve. We obtained responses of single nerve fibers of anesthetized macaque monkeys and cats to a suprathreshold, wideband, multicomponent stimulus designed to allow characterization of spectral filtering at any cochlear locus. Quantitatively the differences between the two species are smaller than in previous studies, but consistent with these studies the filters obtained show a trend of sharper tuning in macaque, relative to the cat, for fibers in the basal half of the cochlea. We also examined differences in group delay measured on the phase data near the characteristic frequency versus in the low-frequency tail. The phase data are consistent with the interpretation of sharper frequency tuning in monkey in the basal half of the cochlea. We conclude that use of suprathreshold, wide-band stimuli supports the interpretation of sharper frequency selectivity in macaque nerve fibers relative to the cat, although the difference is less marked than apparent from the assessment with tonal threshold-based data.

Risk factors and outcomes in patients with cochlear nerve deficiency.

INTRODUCTION: Cochlear nerve deficiency (CND) is a cause of sensorineural hearing loss made by radiologic criteria. There is sparse literature involving audiological outcomes and cochlear implantation (CI) success in patients with CND. METHODS: A retrospective chart review of all patients with sensorineural hearing loss at a tertiary children's hospital from 2000 to 2020 was conducted. Patients with CND on radiographic imaging were included and categorized as hypoplastic, aplastic, or indeterminate. RESULTS: In this study, 53 patients were identified with CND, totaling 70 ears. Of the 53 patients, 30 (56.6 %) were male, 8 (16.0 %) had a family history of childhood hearing loss, 6 (11.3 %) were born preterm, and 11 (23.4 %) required neonatal intensive care admission. The median maternal age was 29 years old [IQR: 27, 35], and 8 (15 %) patients were born to mothers with diabetes. Of the 70 ears, 49 (70 %) utilized conventional hearing aids, 12 (17.1 %) utilized a bone-anchored hearing aid, and 10 (14.3 %) underwent CI. Of the 10 ears implanted, 4 (40 %) ears had nerves classified as hypoplastic, 3 (30 %) as aplastic, and 3 (30 %) as indeterminate. Improvement in pure tone averages compared to preoperative testing was demonstrated in 8 (80 %), and 6 (60 %) displayed improved speech awareness thresholds. CONCLUSION: This study demonstrates that there may be an association between CND and maternal diabetes and NICU admission. There are variable results with hearing amplification options in patients with CND, and further research is needed to better describe the role of CI, bone-anchored hearing aids and conventional hearing aids in patients with CND.

Mechanisms of age-related hearing loss at the auditory nerve central synapses and postsynaptic neurons in the cochlear nucleus.

Sound information is transduced from mechanical vibration to electrical signals in the cochlea, conveyed to and further processed in the brain to form auditory perception. During the process, spiral ganglion neurons (SGNs) are the key cells that connect the peripheral and central auditory systems by receiving information from hair cells in the cochlea and transmitting it to neurons of the cochlear nucleus (CN). Decades of research in the cochlea greatly improved our understanding of SGN function under normal and pathological conditions, especially about the roles of different subtypes of SGNs and their peripheral synapses. However, it remains less clear how SGN central terminals or auditory nerve (AN) synapses connect to CN neurons, and ultimately how peripheral pathology links to structural alterations and functional deficits in the central auditory nervous system. This review discusses recent progress about the morphological and physiological properties of different subtypes of AN synapses and associated postsynaptic CN neurons, their changes during aging, and the potential mechanisms underlying age-related hearing loss.

Auditory robustness and resilience in the aging auditory system of the desert locust.

After overexposure to loud music, we experience a decrease in our ability to hear (robustness), which usually recovers (resilience). Here, we exploited the amenable auditory system of the desert locust, Schistocerca gregaria, to measure how robustness and resilience depend on age. We found that gene expression changes are dominated by age as opposed to noise exposure. We measured sound-evoked nerve activity for young and aged locusts directly, after 24 hours and 48 hours after noise exposure. We found that both young and aged locusts recovered their auditory nerve function over 48 hours. We also measured the sound-evoked transduction current in individual auditory neurons, and although the transduction current magnitude recovered in the young locusts after noise exposure, it failed to recover in the aged locusts. A plastic mechanism compensates for the decreased transduction current in aged locusts. We suggest key genes upregulated in young noise-exposed locusts that mediate robustness to noise exposure and find potential candidates responsible for compensatory mechanisms in the auditory neurons of aged noise-exposed locusts.

Vestibular function in children with vestibulocochlear nerve aplasia/hypoplasia.

BACKGROUND: Infants and young children with vestibulocochlear nerve (VCN) hypoplasia/aplasia present with severe hearing loss and are candidates for cochlear implantation (CI). It is unknown whether vestibular function is related to CI outcome and if vestibular tests can guide the operation decision. AIMS/OBJECTIVES: Our aim was to describe the vestibular function in patients with VCN hypoplasia/aplasia before a possible CI. MATERIALS AND METHODS: Forty-two ears in 23 patients were tested between 2019 and 2022 with bone-conducted cervical vestibular evoked myogenic potentials (BCcVEMP), video head impulse test (vHIT) and miniice-water caloric test (mIWC). RESULTS: All ears could be tested with at least one vestibular test and 83% could be tested with more than one method. Twenty-nine ears (61%) showed normal function with at least one method. The presence of a normal response to any test doubled the likelihood of a measured hearing threshold after CI, the best predictors being the BCcVEMP and vHIT (p < 0.05). CONCLUSION: Canal function may represent a predictor of auditive pathway integrity with a possible favourable audiological outcome after CI operation. SIGNIFICANCE: Our results demonstrate high vestibular response rates suggesting a functioning pathway despite the radiological diagnosis.

Ultrastructure of noise-induced cochlear synaptopathy.

Acoustic overexposure can eliminate synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs), even if hair-cell function recovers. This synaptopathy has been extensively studied by confocal microscopy, however, understanding the nature and sequence of damage requires ultrastructural analysis. Here, we used focused ion-beam scanning electron microscopy to mill, image, segment and reconstruct ANF terminals in mice, 1 day and 1 week after synaptopathic exposure (8-16 kHz, 98 dB SPL). At both survivals, ANF terminals were normal in number, but 62% and 53%, respectively, lacked normal synaptic specializations. Most non-synapsing fibers (57% and 48% at 1 day and 1 week) remained in contact with an IHC and contained healthy-looking organelles. ANFs showed a transient increase in mitochondrial content (51%) and efferent innervation (34%) at 1 day. Fibers maintaining synaptic connections showed hypertrophy of pre-synaptic ribbons at both 1 day and 1 week. Non-synaptic fibers were lower in mitochondrial content and typically on the modiolar side of the IHC, where ANFs with high-thresholds and low spontaneous rates are normally found. Even 1 week post-exposure, many ANF terminals remained in IHC contact despite loss of synaptic specializations, thus, regeneration efforts at early post-exposure times should concentrate on synaptogenesis rather than neurite extension.

From the outer ear to the nerve: A complete computer model of the peripheral auditory system.

Computer models of the individual components of the peripheral auditory system - the outer, middle, and inner ears and the auditory nerve - have been developed in the past, with varying level of detail, breadth, and faithfulness of the underlying parameters. Building on previous work, we advance the modeling of the ear by presenting a complete, physiologically justified, bottom-up computer model based on up-to-date experimental data that integrates all of these parts together seamlessly. The detailed bottom-up design of the present model allows for the investigation of partial hearing mechanisms and their defects, including genetic, molecular, and microscopic factors. Also, thanks to the completeness of the model, one can study microscopic effects in the context of their implications on hearing as a whole, enabling the correlation with neural recordings and non-invasive psychoacoustic methods. Such a model is instrumental for advancing quantitative understanding of the mechanism of hearing, for investigating various forms of hearing impairment, as well as for devising next generation hearing aids and cochlear implants.

The efficacy of a TrkB monoclonal antibody agonist in preserving the auditory nerve in deafened guinea pigs.

The auditory nerve typically degenerates following loss of cochlear hair cells or synapses. In the case of hair cell loss neural degeneration hinders restoration of hearing through a cochlear implant, and in the case of synaptopathy suprathreshold hearing is affected, potentially degrading speech perception in noise. It has been established that neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) can mitigate auditory nerve degeneration. Several potential BDNF mimetics have also been investigated for neurotrophic effects in the cochlea. A recent in vitro study showed favorable effects of M3, a TrkB monoclonal antibody agonist, when compared with BDNF. In the present study we set out to examine the effect of M3 on auditory nerve preservation in vivo. Thirty-one guinea pigs were bilaterally deafened, and unilaterally treated with a single 3-µl dose of 7 mg/ml, 0.7 mg/ml M3 or vehicle-only by means of a small gelatin sponge two weeks later. During the experiment and analyses the experimenters were blinded to the three treatment groups. Four weeks after treatment, we assessed the treatment effect (1) histologically, by quantifying survival of SGCs and their peripheral processes (PPs); and (2) electrophysiologically, with two different paradigms of electrically evoked compound action potential (eCAP) recordings shown to be indicative of neural health: single-pulse stimulation with varying inter-phase gap (IPG), and pulse-train stimulation with varying inter-pulse interval. We observed a consistent and significant preservative effect of M3 on SGC survival in the lower basal turn (approximately 40% more survival than in the untreated contralateral cochlea), but also in the upper middle and lower apical turn of the cochlea. This effect was similar for the two treatment groups. Survival of PPs showed a trend similar to that of the SGCs, but was only significantly higher for the highest dose of M3. The protective effect of M3 on SGCs was not reflected in any of the eCAP measures: no statistically significant differences were observed between groups in IPG effect nor between the M3 treatment groups and the control group using the pulse-train stimulation paradigm. In short, while a clear effect of M3 was observed on SGC survival, this was not clearly translated into functional preservation.

Role of Cochlear Nerve Diameter as a Prognostic Indicator for Hearing Recovery in Older Adults with Idiopathic Sudden Sensorineural Hearing Loss.

BACKGROUND: Idiopathic sudden sensorineural hearing loss is a disabling condition that lowers the quality of life specifically in older adults living alone. It is crucial to determine the outcome of the disease and to offer early treatment to prevent isolation caused by hearing impairment in this population. The objective of our study was to investigate whether the initial cochlear nerve thickness may predict the outcome of hearing recovery in older adults with idiopathic sudden sensorineural hearing loss. METHODS: The study population was composed of older adults that were referred with idiopathic sudden sensorineural hearing loss in 1 ear. Long-term audiological data of the cohort were analyzed according to Siegel's criteria on hearing recovery and were grouped according to complete recovery or treatment failure. Cochlear nerve diameters of the diseased and safe ears of each group, measured on reformatted images on magnetic resonance imaging, at the fundus, in the mid-internal acoustic canal, and at the entry point into the Pons were compared in each group and between groups. RESULTS: Mean cochlear nerve diameter was significantly larger in the recovered older adults (1.11 ± 0.27 mm) than in the non-recovered adults (0.94 ± 0.21 mm) at the mid-internal acoustic canal (Student's t-test, P < .05). Cochlear nerve thickness at mid-internal acoustic canal (≤0.8 mm) sensitivity for recovery failure was 89% and displayed an odds ratio 5.333, 95% CI (1.000-28.435). CONCLUSION: Cochlear nerve thickness in mid-internal acoustic canal in non-recovered older adults with idiopathic sudden sensorineural hearing loss is significantly thinner than the completely recovered group. Older adults with mid-internal acoustic canal cochlear nerve greatest diameter cutoff level of ≤0.8 mm are 5.33 times more exposed to recovery failure.

Histological Correlates of Auditory Nerve Injury from Kainic Acid in the Budgerigar (Melopsittacus undulatus).

PURPOSE: Loss of auditory nerve afferent synapses with cochlear hair cells, called cochlear synaptopathy, is a common pathology in humans caused by aging and noise overexposure. The perceptual consequences of synaptopathy in isolation from other cochlear pathologies are still unclear. Animal models provide an effective approach to resolve uncertainty regarding the physiological and perceptual consequences of auditory nerve loss, because neural lesions can be induced and readily quantified. The budgerigar, a parakeet species, has recently emerged as an animal model for synaptopathy studies based on its capacity for vocal learning and ability to behaviorally discriminate simple and complex sounds with acuity similar to humans. Kainic acid infusions in the budgerigar produce a profound reduction of compound auditory nerve responses, including wave I of the auditory brainstem response, without impacting physiological hair cell measures. These results suggest selective auditory nerve damage. However, histological correlates of neural injury from kainic acid are still lacking. METHODS: We quantified the histological effects caused by intracochlear infusion of kainic acid (1 mM; 2.5 µL), and evaluated correlations between the histological and physiological assessments of auditory nerve status. RESULTS: Kainic acid infusion in budgerigars produced pronounced loss of neural auditory nerve soma (60% on average) in the cochlear ganglion, and of peripheral axons, at time points 2 or more months following injury. The hair cell epithelium was unaffected by kainic acid. Neural loss was significantly correlated with reduction of compound auditory nerve responses and auditory brainstem response wave I. CONCLUSION: Compound auditory nerve responses and wave I provide a useful index of cochlear synaptopathy in this animal model.