Auditory Brainstem Response Data Research Articles

Paired measurements of cochlear function and hair cell count in Dutch-belted rabbits with noise-induced hearing loss

The effects of noise-induced hearing loss have yet to be studied for the Dutch-belted strain of rabbits, which is the only strain that has been used in studies of the central auditory system. We measured auditory brainstem responses (ABRs), 2f1−f2 distortion product otoacoustic emissions (DPOAEs), and counts of cochlear inner and outer hair cells (IHCs and OHCs, respectively) from confocal images of Myo7a-stained cochlear whole-mounts in unexposed and noise-overexposed, Dutch-belted, male and female rabbits in order to characterize cochlear function and structure under normal-hearing and hearing-loss conditions. Using an octave-band noise exposure centered at 750 Hz presented under isoflurane anesthesia, we found that a sound level of 133 dB SPL for 60 min was minimally sufficient to produce permanent ABR threshold shifts. Overexposure durations of 60 and 90 min caused median click-evoked ABR threshold shifts of 10 and 50 dB, respectively. Susceptibility to overexposure was highly variable across ears, but less variable across test frequencies within the same ear. ABR and DPOAE threshold shifts were smaller, on average, and more variable in male than female ears. Similarly, post-exposure survival of OHCs was higher, on average, and more variable in male than female ears. We paired post-exposure ABR and DPOAE threshold shift data with hair cell count data measured in the same ear at the same frequency and cochlear frequency location. ABR and DPOAE threshold shifts exhibited critical values of 46 and 18 dB, respectively, below which the majority of OHCs and IHCs survived and above which OHCs were wiped out while IHC survival was variable. Our data may be of use to researchers who wish to use Dutch-belted rabbits as a model for the effects of noise-induced hearing loss on the central auditory system.

A broad filter between call frequency and peripheral auditory sensitivity in northern grasshopper mice (Onychomys leucogaster).

Acoustic communication is a fundamental component of mate and competitor recognition in a variety of taxa and requires animals to detect and differentiate among acoustic stimuli (Bradbury and Vehrencamp in Principles of animal communication, 2nd edn., Sinauer Associates, Sunderland, 2011). The matched filter hypothesis predicts a correspondence between peripheral auditory tuning of receivers and properties of species-specific acoustic signals, but few studies have assessed this relationship in rodents. We recorded vocalizations and measured auditory brainstem responses (ABRs) in northern grasshopper mice (Onychomys leucogaster), a species that produces long-distance calls to advertise their presence to rivals and potential mates. ABR data indicate the highest sensitivity (28.33 ± 9.07dB SPL re: 20μPa) at 10kHz, roughly corresponding to the fundamental frequency (11.6 ± 0.63kHz) of long-distance calls produced by conspecifics. However, the frequency range of peripheral auditory sensitivity was broad (8-24kHz), indicating the potential to detect both the harmonics of conspecific calls and vocalizations of sympatric heterospecifics. Our findings provide support for the matched filter hypothesis extended to include other ecologically relevant stimuli. Our study contributes important baseline information about the sensory ecology of a unique rodent to the study of sound perception.

Effects of presentation rate and onset time on auditory brainstem responses in Northern saw-whet owls (Aegolius acadicus).

Monitoring auditory brainstem responses (ABRs) is a common method of assessing auditory processing in non-model species. Although ABRs are widely used to compare auditory abilities across taxa, the extent to which different features of acoustic stimuli affect the ABR is largely unknown in most non-mammalian species. The authors investigated the effects of varying presentation rate and onset time to determine how different features of acoustic stimuli influence the ABR in Northern saw-whet owls (Aegolius acadicus), a species known for their unique auditory adaptations and hunting abilities. At presentation rates ranging from 21.1 to 51.1 s-1, there were no differences in the size or synchrony of ABRs, suggesting that stimuli can be presented at a relatively rapid rate to maximize the number of observations recorded for analysis. While increasing onset time was associated with a decrement in response size and synchrony, tonebursts with 1 ms onset times produced overgeneralized neural responses as a result of spectral splatter. This suggests that 2 to 3 ms onset times may balance the trade-off between response synchrony and frequency specificity when comparing relative neural recruitment across frequencies. These findings highlight the importance of considering stimulus parameters when interpreting ABR data.

The distribution of calbindin-D28k, parvalbumin, and calretinin immunoreactivity in the inferior colliculus of circling mouse.

The circling mice with tmie gene mutation are known as an animal deafness model, which showed hyperactive circling movement. Recently, the reinvestigation of circling mouse was performed to check the inner ear pathology as a main lesion of early hearing loss. In this trial, the inner ear organs were not so damaged to cause the hearing deficit of circling (cir/cir) mouse at 18 postnatal day (P18) though auditory brainstem response data indicated hearing loss of cir/cir mice at P18. Thus, another mechanism may be correlated with the early hearing loss of cir/cir mice at P18. Hearing loss in the early life can disrupt the ascending and descending information to inferior colliculus (IC) as integration site. There were many reports that hearing loss could result in the changes in Ca2+ concentration by either cochlear ablation or genetic defect. However, little was known to be reported about the correlation between the pathology of IC and Ca2+ changes in circling mice. Therefore, the present study investigated the distribution of calcium-binding proteins (CaBPs), calbindin-D28k, parvalbumin, and calretinin immunoreactivity (IR) in the IC to compare among wild-type (+/+), heterozygous (+/cir), and homozygous (cir/cir) mice by immunohistochemistry. The decreases of CaBPs IR in cir/cir were statistically significant in the neurons as well as neuropil of IC. Thus, this study proposed overall distributional alteration of CaBPs IR in the IC caused by early hearing defect and might be helpful to elucidate the pathology of central auditory disorder related with Ca2+ metabolism.

Label-Free Ferrocene-Loaded Nanocarrier Engineering for In Vivo Cochlear Drug Delivery and Imaging

It is hypothesized that ferrocene (FC)-loaded nanocarriers (FC-NCs) are safe label-free contrast agents for cochlear biodistribution study by transmission electron microscopy (TEM). To test this hypothesis, after engineering, the poly(epsilon-caprolactone)/polyglycolide NCs are tested for stability with various types and ratios of sugar cryoprotectants during freeze-drying. Their physicochemical properties are characterized by UV-visible spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM/EDS). The biodistribution of the FC-NCs in the cochlear tissue after intratympanic injection in guinea pigs is visualized by TEM. Auditory brainstem responses are measured before and after 4-day treatments. These FC-NCs have 153.4 ± 8.7 nm, 85.5 ± 11.2%, and -22.1 ± 1.1 mV as mean diameters, percent drug association efficiency, and zeta potential, respectively (n = 3). The incorporation of FC into the NCs is confirmed by Fourier transform infrared spectroscopy and SEM/EDS spectra. Lactose (3:1 ratio, v/v) is the most effective stabilizer after a 12-day study. The administered NCs are visible by TEM in the scala media cells of the cochlea. Based on auditory brainstem response data, FC-NCs do not adversely affect hearing. Considering the electrondense, radioactive, and magnetic properties of iron inside FC, FC-NCs are promising nanotemplate for future inner ear theranostics.

Impact of monaural frequency compression on binaural fusion at the brainstem level.

A classical objective measure for binaural fusion at the brainstem level is the so-called β-wave of the binaural interaction component (BIC) in the auditory brainstem response (ABR). However, in some cases it appeared that a reliable detection of this component still remains a challenge. In this study, we investigate the wavelet phase synchronization stability (WPSS) of ABR data for the analysis of binaural fusion and compare it to the BIC. In particular, we examine the impact of monaural nonlinear frequency compression on binaural fusion. As the auditory system is tonotopically organized, an interaural frequency mismatch caused by monaural frequency compression could negatively effect binaural fusion. In this study, only few subjects showed a detectable β-wave and in most cases only for low ITDs. However, we present a novel objective measure for binaural fusion that outperforms the current state-of-the-art technique (BIC): the WPSS analysis showed a significant difference between the phase stability of the sum of the monaurally evoked responses and the phase stability of the binaurally evoked ABR. This difference could be an indicator for binaural fusion in the brainstem. Furthermore, we observed that monaural frequency compression could indeed effect binaural fusion, as the WPSS results for this condition vary strongly from the results obtained without frequency compression.

Modeling and estimation of single-trial event-related potentials using partially observed diffusion processes

This paper proposes a new modeling framework for estimating single-trial event-related potentials (ERPs). Existing studies based on state-space approach use discrete-time random-walk models. We propose to use continuous-time partially observed diffusion process which is more natural and appropriate to describe the continuous dynamics underlying ERPs, discretely observed in noise as single-trials. Moreover, the flexibility of the continuous-time model being specified and analyzed independently of observation intervals, enables a more efficient handling of irregularly or variably sampled ERPs than its discrete-time counterpart which is fixed to a particular interval. We consider the Ornstein–Uhlenbeck (OU) process for the inter-trial parameter dynamics and further propose a nonlinear process of Cox, Ingersoll & Ross (CIR) with a heavy-tailed density to better capture the abrupt changes. We also incorporate a single-trial trend component using the mean-reversion variant, and a stochastic volatility noise process. The proposed method is applied to analysis of auditory brainstem responses (ABRs). Simulation shows that both diffusions give satisfactory tracking performance, particularly of the abrupt ERP parameter variations by the CIR process. Evaluation on real ABR data across different subjects, stimulus intensities and hearing conditions demonstrates the superiority of our method in extracting the latent single-trial dynamics with significantly improved SNR, and in detecting the wave V which is critical for diagnosis of hearing loss. Estimation results on data with variable sampling frequencies and missing single-trials show that the continuous-time diffusion model can capture more accurately the inter-trial dynamics between varying observation intervals, compared to the discrete-time model.

Ups and Downs of Viagra: Revisiting Ototoxicity in the Mouse Model

Sildenafil citrate (Viagra), a phosphodiesterase 5 inhibitor (PDE5i), is a commonly prescribed drug for erectile dysfunction. Since the introduction of Viagra in 1997, several case reports have linked Viagra to sudden sensorineural hearing loss. However, these studies are not well controlled for confounding factors, such as age and noise-induced hearing loss and none of these reports are based on prospective double-blind studies. Further, animal studies report contradictory data. For example, one study (2008) reported hearing loss in rats after long-term and high-dose exposure to sildenafil citrate. The other study (2012) showed vardenafil, another formulation of PDE5i, to be protective against noise-induced hearing loss in mice and rats. Whether or not clinically relevant doses of sildenafil citrate cause hearing loss in normal subjects (animals or humans) is controversial. One possibility is that PDE5i exacerbates age-related susceptibility to hearing loss in adults. Therefore, we tested sildenafil citrate in C57BL/6J, a strain of mice that displays increased susceptibility to age-related hearing loss, and compared the results to those obtained from the FVB/N, a strain of mice with no predisposition to hearing loss. Six-week-old mice were injected with the maximum tolerated dose of sildenafil citrate (10 mg/kg/day) or saline for 30 days. Auditory brainstem responses (ABRs) were recorded pre- and post injection time points to assess hearing loss. Entry of sildenafil citrate in the mouse cochlea was confirmed by qRT-PCR analysis of a downstream target of the cGMP-PKG cascade. ABR data indicated no statistically significant difference in hearing between treated and untreated mice in both backgrounds. Results show that the maximum tolerated dose of sildenafil citrate administered daily for 4 weeks does not affect hearing in the mouse. Our study gives no indication that Viagra will negatively impact hearing and it emphasizes the need to revisit the issue of Viagra related ototoxicity in humans.

AUTOMATED AVERAGING OF AUDITORY EVOKED RESPONSE WAVEFORMS USING WAVELET ANALYSIS

The auditory brainstem response (ABR) is widely used as an index to assist hearing and brain function diagnoses. In particular, in clinical applications, the rapid detection of ABR peak characteristics is required. One approach to improving the speed of detection is to decrease the number of signal averaging procedures while denoising during the detection of ABR waveforms; another approach is to extract the characteristics of ABR waveform components. In our previous study, to represent ABR waveform components, we obtained not only the frequency characteristics of an ABR but also the frequency characteristics of each component of the ABR based on the time (latency). Using a one-dimensional discrete wavelet transform (DWT) in this latency-frequency analysis, we described an approximate method of reproducing ABR signals with a low SNR from observed values obtained with a smaller number of averaging procedures. At the same time, using this multiple-level frequency decomposition of ABR signals according to the known frequency content of the ABR, we extracted the peak latency of the fast component of the ABR using fewer averagings of the ABR data. From these decomposition and reconstruction results for ABR signals, we proposed the optimal decomposition level of the ABR and explained how we used the waveform of the ABR reconstructed by the inverse DWT (IDWT). In this paper, we propose a method of automated averaging of the ABR using the waveform reconstructed by discrete wavelet multiresolution analysis (MRA). Our proposed method will be useful for the fast detection of ABR latency characteristics in hearing screening test.

Can subject-specific single-fibre electrically evoked auditory brainstem response data be predicted from a model?

This article investigates whether prediction of subject-specific physiological data is viable through an individualised computational model of a cochlear implant. Subject-specific predictions could be particularly useful to assess and quantify the peripheral factors that cause inter-subject variations in perception. The results of such model predictions could potentially be translated to clinical application through optimisation of mapping parameters for individual users, since parameters that affect perception would be reflected in the model structure and parameters. A method to create a subject-specific computational model of a guinea pig with a cochlear implant is presented. The objectives of the study are to develop a method to construct subject-specific models considering translation of the method to in vivo human models and to assess the effectiveness of subject-specific models to predict peripheral neural excitation on subject level. Neural excitation patterns predicted by the model are compared with single-fibre electrically evoked auditory brainstem responses obtained from the inferior colliculus in the same animal. Results indicate that the model can predict threshold frequency location, spatial spread of bipolar and tripolar stimulation and electrode thresholds relative to one another where electrodes are located in different cochlear structures. Absolute thresholds and spatial spread using monopolar stimulation are not predicted accurately. Improvements to the model should address this.

Analysis of the variability of auditory brainstem response components through linear regression

The analysis of the Auditory Brainstem Response (ABR) is of fundamental importance to the investigation of the auditory system behavior, though its interpretation has a subjective nature because of the manual process employed in its study and the clinical experience required for its analysis. When analyzing the ABR, clinicians are often interested in the identification of ABR signal components referred to as Jewett waves. In particular, the detection and study of the time when these waves occur (i.e., the wave latency) is a practical tool for the diagnosis of disorders affecting the auditory system. In this context, the aim of this research is to compare ABR manual/visual analysis provided by different examiners. Methods: The ABR data were collected from 10 normal-hearing subjects (5 men and 5 women, from 20 to 52 years). A total of 160 data samples were analyzed and a pair- wise comparison between four distinct examiners was executed. We carried out a statistical study aiming to identify significant differences between assessments provided by the examiners. For this, we used Linear Regression in conjunction with Bootstrap, as a method for evaluating the relation between the responses given by the examiners. Results: The analysis suggests agreement among examiners however reveals differences between assessments of the variability of the waves. We quantified the magnitude of the obtained wave latency differences and 18% of the investigated waves presented substantial differences (large and moderate) and of these 3.79% were considered not acceptable for the clinical practice. Conclusions: Our results characterize the variability of the manual analysis of ABR data and the necessity of establishing unified standards and protocols for the analysis of these data. These results may also contribute to the validation and development of automatic systems that are employed in the early diagnosis of hearing loss.

Assessment of inter-examiner agreement and variability in the manual classification of auditory brainstem response

BackgroundThe analysis of the Auditory Brainstem Response (ABR) is of fundamental importance to the investigation of the auditory system behaviour, though its interpretation has a subjective nature because of the manual process employed in its study and the clinical experience required for its analysis. When analysing the ABR, clinicians are often interested in the identification of ABR signal components referred to as Jewett waves. In particular, the detection and study of the time when these waves occur (i.e., the wave latency) is a practical tool for the diagnosis of disorders affecting the auditory system. Significant differences in inter-examiner results may lead to completely distinct clinical interpretations of the state of the auditory system. In this context, the aim of this research was to evaluate the inter-examiner agreement and variability in the manual classification of ABR.MethodsA total of 160 ABR data samples were collected, for four different stimulus intensity (80dBHL, 60dBHL, 40dBHL and 20dBHL), from 10 normal-hearing subjects (5 men and 5 women, from 20 to 52 years). Four examiners with expertise in the manual classification of ABR components participated in the study. The Bland-Altman statistical method was employed for the assessment of inter-examiner agreement and variability. The mean, standard deviation and error for the bias, which is the difference between examiners’ annotations, were estimated for each pair of examiners. Scatter plots and histograms were employed for data visualization and analysis.ResultsIn most comparisons the differences between examiner’s annotations were below 0.1 ms, which is clinically acceptable. In four cases, it was found a large error and standard deviation (>0.1 ms) that indicate the presence of outliers and thus, discrepancies between examiners.ConclusionsOur results quantify the inter-examiner agreement and variability of the manual analysis of ABR data, and they also allows for the determination of different patterns of manual ABR analysis.

The Auditory Brainstem Response: Latencies Obtained in Children While under General Anesthesia

The auditory brainstem response (ABR) test is frequently employed to estimate hearing sensitivity and assess the integrity of the ascending auditory system. In persons who cannot participate in conventional tests of hearing, a short-acting general anesthetic is used, recordings are obtained, and the results are compared with normative data. However, several factors (e.g., anesthesia, temperature changes) can contribute to delayed absolute and interpeak latencies, making it difficult to evaluate the integrity of the person's auditory brainstem function. In this study, we investigated the latencies of ABR responses in children who received general anesthesia. Between subject. Twelve children between the ages of 29 and 52 mo, most of whom exhibited a developmental delay but normal peripheral auditory function, comprised the anesthesia group. Twelve participants between the ages of 13 and 26 yr with normal hearing thresholds comprised the control group. ABRs from a single ear from children, recorded under general anesthesia, were retrospectively analyzed and compared to those obtained from a control group with no anesthesia. ABRs were generated using 80 dB nHL rarefaction click stimuli. T-tests, corrected for alpha slippage, were employed to examine latency differences between groups. There were significant delays in latencies for children evaluated under general anesthesia compared to the control group. Delays were observed for wave V and the interpeak intervals I-III, III-V, and I-V. Our data suggest that caution is needed in interpreting neural function from ABR data recorded while a child is under general anesthesia.

Auditory brainstem response classification for threshold detection using estimated evoked potential data: comparison with ensemble averaged data

Auditory brainstem response (ABR) has become a routine clinical tool in neurological and audiological assessment. ABR measurement process with ensemble averaging is very time-consuming and uncomfortable for subjects due to the more repetition of single trials. This condition also restricts the wide usability of ABR in clinical applications. Therefore, the reduction in repetitions has a great importance in ABR measurements. In this study, 488 ABR responses are used for creating two different data sets. The first set is created conventionally by ensemble averaging of 1,024 single trials for each ABR pattern. The second set is obtained from the first estimated 64 single trials of the same records for each ABRs. Estimation is realized by using a nonlinear adaptive filtering algorithm. In classification stage, a powerful classifier integrated with a feature selection algorithm is performed for each data set. In result, the classification performance for estimated ABR data with 64 repetitions is better than the classification performance of the ensemble averaged data with 1,024 repetitions. The proposed system is resulted in an accuracy of 96% for estimated ABRs. So, the proposed system can effectively be used for threshold detection in auditory assessment providing a high accuracy. While the obtained results contribute to the practical ABR usage in clinics, the great significance of it arises from the reduction in repetitions via estimation of ABRs.

Early developmental expression of connexin26 in the cochlea contributes to its dominate functional role in the cochlear gap junctions

Mutations in Gjb2 and Gjb6 genes, coding for connexin26 (Cx26) and Cx30 proteins, respectively, are linked to about half of all cases of human autosomal non-syndromic prelingual deafness. Molecular mechanisms of the hearing impairments, however, are unclear. Most cochlear gap junctions (GJs) are co-assembled from Cx26 and Cx30 and deletion of either one of them causes deafness. Our previous studies have shown that normal hearing is possible in the absence of the Cx30 gene when Cx26 is over-expressed. To further test unique functional requirements for various types of connexins in the hearing, we investigated whether the hearing in the conditional Cx26 (cCx26) null mice could be rescued by genetically over-expressing Cx30.Multiple lines of control and experimental mouse models were used. Auditory brainstem response (ABR) measurements showed normal hearing in targeted gene deletion mice when the deleted Cx26 or Cx30 was transgenically expressed from integrated bacterial artificial chromosome (BAC), demonstrating the effectiveness of the BAC rescue approach. In contrast, severe hearing loss was found in cCx26 null mice in which Cx30 was over-expressed. Morphology observations were consistent with the ABR data. Cochleae of cCx26 null mice with and without the transgenic over-expression of Cx30 both showed the typical immature feature of postnatal cochlear development-the closed tunnel of Corti. Immunolabeling data and Western blot quantification indicated that the Cx26 protein expression preceded that of Cx30 during the early postnatal period in the cochlea. Null expression of Cx26 may therefore uniquely result in a transient period when a total elimination of GJs in functionally-important regions of the developing cochlea is possible. We conclude that Cx26 plays an essential role in the development of the auditory sensory epithelium and its unique developmental functions required for normal hearing is not replaceable by Cx30.

Evaluation of wavelet techniques in rapid extraction of ABR variations from underlying EEG

The aim of this study is to analyse an effective wavelet method for denoising and tracking temporal variations of the auditory brainstem response (ABR). The rapid and accurate extraction of ABRs in clinical practice has numerous benefits, including reductions in clinical test times and potential long-term patient monitoring applications. One method of achieving rapid extraction is through the application of wavelet filtering which, according to earlier research, has shown potential in denoising signals with low signal-to-noise ratios. The research documented in this paper evaluates the application of three such wavelet approaches on a common set of ABR data collected from eight participants. We introduced the use of the latency–intensity curve of ABR wave V for performance evaluation of tracking temporal variations. The application of these methods to the ABR required establishing threshold functions and time windows as an integral part of the research. Results revealed that the cyclic-shift-tree-denoising performed superior compared to other tested approaches. This required an ensemble of only 32 epochs to extract a fully featured ABR compared to the 1024 epochs with conventional ABR extraction based on linear moving time averaging.

The Manipulation of Auditory Brain Stem Response Data to Predict the Behavioral Audiogram during Infancy

The auditory brain stem response (ABR) is the current gold standard to estimate hearing thresholds during infancy. The clinical protocols to illicit the ABR are documented, and the correlation between the ABR and auditory sensitivity has been validated extensively. Research also has focused on the maturation of the auditory system and its effects on the ABR threshold. In situ ABR measures were conducted to quantify the maturation of the ABR during infancy for the purposes of controlling for this effect when using ABR thresholds to estimate hearing levels on an audiogram. This article describes a corrective procedure that permits the clinician to obtain the estimated hearing level from ABR thresholds during infancy when immature responses are prevalent.

Clinical Status of the Auditory Steady-State Response in Infants

Pediatric audiology has seen the inclusion of the auditory steady-state response (ASSR) in clinical test batteries as a valuable diagnostic tool. Its unique stimuli, recording and analysis characteristics allow for applications not previously possible with other auditory evoked responses in infants and young children. Although the long-standing research and clinical validation history of the frequency-specific auditory brain stem response (ABR) make it the current gold standard for estimating hearing thresholds, accumulating evidence is establishing the ASSR as a reliable and accurate tool for the diagnosis of hearing loss in infants. Current test-protocol efficiency and accuracy may be improved by including the ASSR to supplement ABR data and to cross-check test results. This article reviews the ASSR and its current clinical applications and limitations for determining hearing thresholds in infants and young children.

On auditory neuropathy, aka auditory neuropathy spectrum

On auditory neuropathy, aka auditory neuropathy spectrum

A mouse model with postnatal endolymphatic hydrops and hearing loss

Endolymphatic hydrops (ELH), hearing loss and neuronal degeneration occur together in a variety of clinically significant disorders, including Meniere’s disease (MD). However, the sequence of these pathological changes and their relationship to each other are not well understood. In this regard, an animal model that spontaneously develops these features postnatally would be useful for research purposes. A search for such a model led us to the Phex Hyp-Duk mouse, a mutant allele of the Phex gene causing X-linked hypophosphatemic rickets. The hemizygous male ( Phex Hyp-Duk /Y) was previously reported to exhibit various abnormalities during adulthood, including thickening of bone, ELH and hearing loss. The reported inner-ear phenotype was suggestive of progressive pathology and spontaneous development of ELH postnatally, but not conclusive. The main focuses of this report are to further characterize the inner ear phenotype in Phex Hyp-Duk /Y mice and to test the hypotheses that (a) the Phex Hyp-Duk /Y mouse develops ELH and hearing loss postnatally, and (b) the development of ELH in the Phex Hyp-Duk /Y mouse is associated with obstruction of the endolymphatic duct (ED) due to thickening of the surrounding bone. Auditory brainstem response (ABR) recordings at various times points and histological analysis of representative temporal bones reveal that Phex Hyp-Duk /Y mice typically develop adult onset, asymmetric, progressive hearing loss closely followed by the onset of ELH. ABR and histological data show that functional degeneration precedes structural degeneration. The major degenerative correlate of hearing loss and ELH in the mutants is the primary loss of spiral ganglion cells. Further, Phex Hyp-Duk /Y mice develop ELH without evidence of ED obstruction, supporting the idea that ELH can be induced by a mechanism other than the blockade of longitudinal flow of endolymphatic fluid, and occlusion of ED is not a prerequisite for the development of ELH in patients.