Abnormal white and gray matter functional connectivity is associated with cognitive dysfunction in presbycusis.

Presbycusis is characterized by high-frequency hearing loss and is closely associated with cognitive decline. Previous studies have observed functional reorganization of gray matter in presbycusis, but the information transmission between gray matter and white matter remains ill-defined. Using resting-state functional magnetic resonance imaging, we investigated differences in functional connectivity (GM-GM, WM-WM, and GM-WM) between 60 patients with presbycusis and 57 healthy controls. Subsequently, we examined the correlation between these connectivity differences with high-frequency hearing loss as well as cognitive impairment. Our results revealed significant alterations in functional connectivity involving the body of the corpus callosum, posterior limbs of the internal capsule, retrolenticular region of the internal capsule, and the gray matter regions in presbycusis. Notably, disrupted functional connectivity was observed between the body of the corpus callosum and ventral anterior cingulate cortex in presbycusis, which was associated with impaired attention. Additionally, enhanced functional connectivity was found in presbycusis between the internal capsule and the ventral auditory processing stream, which was related to impaired cognition in multiple domains. These two patterns of altered functional connectivity between gray matter and white matter may involve both bottom-up and top-down regulation of cognitive function. These findings provide novel insights into understanding cognitive compensation and resource redistribution mechanisms in presbycusis.

High-Frequency Sensorineural Hearing Loss Alters Cue-Weighting Strategies for Discriminating Stop Consonants in Noise.

There is increasing evidence that hearing-impaired (HI) individuals do not use the same listening strategies as normal-hearing (NH) individuals, even when wearing optimally fitted hearing aids. In this perspective, better characterization of individual perceptual strategies is an important step toward designing more effective speech-processing algorithms. Here, we describe two complementary approaches for (a) revealing the acoustic cues used by a participant in a /d/-/g/ categorization task in noise and (b) measuring the relative contributions of these cues to decision. These two approaches involve natural speech recordings altered by the addition of a "bump noise." The bumps were narrowband bursts of noise localized on the spectrotemporal locations of the acoustic cues, allowing the experimenter to manipulate the consonant percept. The cue-weighting strategies were estimated for three groups of participants: 17 NH listeners, 18 HI listeners with high-frequency loss, and 15 HI listeners with flat loss. HI participants were provided with individual frequency-dependent amplification to compensate for their hearing loss. Although all listeners relied more heavily on the high-frequency cue than on the low-frequency cue, an important variability was observed in the individual weights, mostly explained by differences in internal noise. Individuals with high-frequency loss relied slightly less heavily on the high-frequency cue relative to the low-frequency cue, compared with NH individuals, suggesting a possible influence of supra-threshold deficits on cue-weighting strategies. Altogether, these results suggest a need for individually tailored speech-in-noise processing in hearing aids, if more effective speech discriminability in noise is to be achieved.

Evidence for age-related cochlear synaptopathy in humans unconnected to speech-in-noise intelligibility deficits.

Cochlear synaptopathy (or the loss of primary auditory synapses) remains a subclinical condition of uncertain prevalence. Here, we investigate whether it affects humans and whether it contributes to suprathreshold speech-in-noise intelligibility deficits. For 94 human listeners with normal audiometry (aged 12-68 years; 64 women), we measured click-evoked auditory brainstem responses (ABRs), self-reported lifetime noise exposure, and speech reception thresholds for sentences (at 65 dB SPL) and words (at 50, 65 and 80 dB SPL) in steady-state and fluctuating maskers. Based on animal research, we assumed that the shallower the rate of growth of ABR wave-I amplitude versus level function, the higher the risk of suffering from synaptopathy. We found that wave-I growth rates decreased with increasing age but not with increasing noise exposure. Speech reception thresholds in noise were not correlated with wave-I growth rates and mean speech reception thresholds were not statistically different for two subgroups of participants (N = 14) with matched audiograms (up to 12 kHz) but different wave-I growth rates. Altogether, the data are consistent with the existence of age-related but not noise-related synaptopathy. In addition, the data dispute the notion that synaptopathy contributes to suprathreshold speech-in-noise intelligibility deficits.

Impaired auditory processing and altered structure of the endbulb of Held synapse in mice lacking the GluA3 subunit of AMPA receptors.

AMPA glutamate receptor complexes with fast kinetics conferred by subunits like GluA3 and GluA4 are essential for temporal precision of synaptic transmission. The specific role of GluA3 in auditory processing and experience related changes in the auditory brainstem remain unknown. We investigated the role of the GluA3 in auditory processing by using wild type (WT) and GluA3 knockout (GluA3-KO) mice. We recorded auditory brainstem responses (ABR) to assess auditory function and used electron microscopy to evaluate the ultrastructure of the auditory nerve synapse on bushy cells (AN-BC synapse). Since labeling for GluA3 subunit increases on auditory nerve synapses within the cochlear nucleus in response to transient sound reduction, we investigated the role of GluA3 in experience-dependent changes in auditory processing. We induced transient sound reduction by plugging one ear and evaluated ABR threshold and peak amplitude recovery for up to 60 days after ear plug removal in WT and GluA3-KO mice. We found that the deletion of GluA3 leads to impaired auditory signaling that is reflected in decreased ABR peak amplitudes, an increased latency of peak 2, early onset hearing loss and reduced numbers and sizes of postsynaptic densities (PSDs) of AN-BC synapses. Additionally, the lack of GluA3 hampers ABR threshold recovery after transient ear plugging. We conclude that GluA3 is required for normal auditory signaling, normal ultrastructure of AN-BC synapses in the cochlear nucleus and normal experience-dependent changes in auditory processing after transient sound reduction.

Expression of amyloid-ß in mouse cochlear hair cells causes an early-onset auditory defect in high-frequency sound perception.

Increasing evidence indicates that defects in the sensory system are highly correlated with age-related neurodegenerative diseases, including Alzheimer's disease (AD). This raises the possibility that sensory cells possess some commonalities with neurons and may provide a tool for studying AD. The sensory system, especially the auditory system, has the advantage that depression in function over time can easily be measured with electrophysiological methods. To establish a new mouse AD model that takes advantage of this benefit, we produced transgenic mice expressing amyloid-ß (Aß), a causative element for AD, in their auditory hair cells. Electrophysiological assessment indicated that these mice had hearing impairment, specifically in high-frequency sound perception (>32 kHz), at 4 months after birth. Furthermore, loss of hair cells in the basal region of the cochlea, which is known to be associated with age-related hearing loss, appeared to be involved in this hearing defect. Interestingly, overexpression of human microtubule-associated protein tau, another factor in AD development, synergistically enhanced the Aß-induced hearing defects. These results suggest that our new system reflects some, if not all, aspects of AD progression and, therefore, could complement the traditional AD mouse model to monitor Aß-induced neuronal dysfunction quantitatively over time.

XBP1 mitigates aminoglycoside-induced endoplasmic reticulum stress and neuronal cell death.

Here we study links between aminoglycoside-induced mistranslation, protein misfolding and neuropathy. We demonstrate that aminoglycosides induce misreading in mammalian cells and assess endoplasmic reticulum (ER) stress and unfolded protein response (UPR) pathways. Genome-wide transcriptome and proteome analyses revealed upregulation of genes related to protein folding and degradation. Quantitative PCR confirmed induction of UPR markers including C/EBP homologous protein, glucose-regulated protein 94, binding immunoglobulin protein and X-box binding protein-1 (XBP1) mRNA splicing, which is crucial for UPR activation. We studied the effect of a compromised UPR on aminoglycoside ototoxicity in haploinsufficient XBP1 (XBP1(+/-)) mice. Intra-tympanic aminoglycoside treatment caused high-frequency hearing loss in XBP1(+/-) mice but not in wild-type littermates. Densities of spiral ganglion cells and synaptic ribbons were decreased in gentamicin-treated XBP1(+/-) mice, while sensory cells were preserved. Co-injection of the chemical chaperone tauroursodeoxycholic acid attenuated hearing loss. These results suggest that aminoglycoside-induced ER stress and cell death in spiral ganglion neurons is mitigated by XBP1, masking aminoglycoside neurotoxicity at the organismal level.

A guinea pig model of selective severe high-frequency hearing loss.

HYPOTHESIS: Using an appropriate dose of an aminoglycoside antibiotic cotreated with a loop diuretic a guinea pig model of high-frequency loss can be obtained mimicking cochlear implant candidates with low-frequency residual hearing. We examined the stability of this model over time. BACKGROUND: A well-established method to create an animal model for profound deafness is cotreatment with an aminoglycoside antibiotic and a loop diuretic. Recent data indicated that reduction of the aminoglycoside dose might yield selective high-frequency hearing loss. Such a model is relevant for studies related to hybrid cochlear implant devices, for example, with respect to preservation of residual hearing. METHODS: Guinea pigs received an electrode for chronic recording of compound action potentials to tones to assess thresholds. They were treated with a coadministration of kanamycin (200 mg/kg) and furosemide (100 mg/kg), after which, the animals were sacrificed for histologic analysis at 2, 4, or 7 weeks. RESULTS: After 2 to 7 weeks threshold shifts were greater than 50 dB for 8 to 16 kHz in 15 of 17 animals, whereas threshold shifts at 2 kHz or lower were less than 50 dB in 13 animals. Major threshold shifts occurred the first 2 to 4 days; subsequently, some spontaneous recovery occurred and, after 2-3 weeks thresholds, remained stable. Inner hair cell loss still progressed between 2 and 4 weeks in the most basal cochlear region; thereafter, hair cell loss was stable. CONCLUSION: An appropriate animal model for selective severe high-frequency hearing loss was obtained, which is stable at 4 weeks after ototoxic treatment.

Frequency discrimination in ears with and without contralateral cochlear dead regions.

OBJECTIVE: The purpose of this study was to test the ability to discriminate low-frequency pure-tone stimuli for ears with and without contralateral dead regions, in subjects with bilateral high-frequency hearing loss; we examined associations between hearing loss characteristics and frequency discrimination of low-frequency stimuli in subjects with high-frequency hearing loss. DESIGN: Cochlear dead regions were diagnosed using the TEN-HL test. A frequency discrimination test utilizing an adaptive three-alternative forced choice method provided difference limens for reference frequencies 0.25 kHz and 0.5 kHz. STUDY SAMPLE: Among 105 subjects with bilateral high-frequency hearing loss, unilateral dead regions were found in 15 subjects. These, and an additional 15 matched control subjects without dead regions, were included in the study. RESULTS: Ears with dead regions performed best at the frequency discrimination test. Ears with a contralateral dead region performed significantly better than ears without a contralateral dead region at 0.5 kHz, the reference frequency closest to the mean audiogram cut-off, while the opposite result was obtained at 0.25 kHz. CONCLUSIONS: Results may be seen as sign of a contralateral effect of unilateral dead regions on the discrimination of stimuli with frequencies well below the audiogram cut-off in adult subjects with bilateral high-frequency hearing loss.

Anti-apoptotic gene Bcl2 is required for stapes development and hearing.

In this paper we describe novel and specific roles for the apoptotic regulators Bcl2 and Bim in hearing and stapes development. Bcl2 is anti-apoptotic while Bim is pro-apoptotic. Characterization of the auditory systems of mice deficient for these molecules revealed that Bcl2⁻/⁻ mice suffered severe hearing loss. This was conductive in nature and did not affect sensory cells of the inner ear, with cochlear hair cells and neurons present and functional. Bcl2⁻/⁻ mice were found to have a malformed, often monocrural, porous stapes (the small stirrup-shaped bone of the middle ear), but a normally shaped malleus and incus. The deformed stapes was discontinuous with the incus and sometimes fused to the temporal bones. The defect was completely rescued in Bcl2⁻/⁻Bim⁻/⁻ mice and partially rescued in Bcl2⁻/⁻Bim⁺/⁻ mice, which displayed high-frequency hearing loss and thickening of the stapes anterior crus. The Bcl2⁻/⁻ defect arose in utero before or during the cartilage stage of stapes development. These results implicate Bcl2 and Bim in regulating survival of second pharyngeal arch or neural crest cells that give rise to the stapes during embryonic development.

Auditory cortex signs of age-related hearing loss.

Age-related hearing loss, or presbyacusis, is a major public health problem that causes communication difficulties and is associated with diminished quality of life. Limited satisfaction with hearing aids, particularly in noisy listening conditions, suggests that central nervous system declines occur with presbyacusis and may limit the efficacy of interventions focused solely on improving audibility. This study of 49 older adults (M = 69.58, SD = 8.22 years; 29 female) was designed to examine the extent to which low and/or high frequency hearing loss was related to auditory cortex morphology. Low and high frequency hearing constructs were obtained from a factor analysis of audiograms from these older adults and 1,704 audiograms from an independent sample of older adults. Significant region of interest and voxel-wise gray matter volume associations were observed for the high frequency hearing construct. These effects occurred most robustly in a primary auditory cortex region (Te1.0) where there was also elevated cerebrospinal fluid with high frequency hearing loss, suggesting that auditory cortex atrophies with high frequency hearing loss. These results indicate that Te1.0 is particularly affected by high frequency hearing loss and may be a target for evaluating the efficacy of interventions for hearing loss.

High-frequency sensorineural hearing loss and its underlying genetics (Hfhl1 and Hfhl2) in NIH Swiss mice.

Studies using inbred strains of mice have been invaluable for identifying alleles that adversely affect hearing. However, the efficacy of those studies is limited by the phenotypes that these strains express and the alleles that they segregate. Here, by selectively breeding phenotypically and genetically heterogeneous NIH Swiss mice, we generated two lines-the all-frequency hearing loss (AFHL) line and the high-frequency hearing loss (HFHL) line-with differential hearing loss. The AFHL line exhibited characteristics typical of severe, early-onset, sensorineural hearing impairment. In contrast, the HFHL line expressed a novel early-onset, mildly progressive, and frequency-specific sensorineural hearing loss. By quantitative trait loci (QTLs) analyses in these two lines, we identified QTLs on chromosomes 7, 8, and 10 that significantly affected hearing function. The loci on chromosomes 7 and 8 (Hfhl1 and Hfhl2, respectively) are novel and appear to adversely affect only high frequencies (≥30 kHz). Mice homozygous for NIH Swiss alleles at either Hfhl1 or Hfhl2 have 32-kHz auditory-evoked brain stem response thresholds that are 8-14 dB SPL higher than the corresponding heterozygotes. DNA sequence analyses suggest that both the Cdh23(ahl) and Gipc3(ahl5) variants contribute to the chromosome 10 QTL detected in the AFHL line. The frequency-specific hearing loss indicates that the Hfhl1 and Hfhl2 alleles may affect tonotopic development. In addition, dissecting the underlying complex genetics of high-frequency hearing loss may prove relevant in identifying less severe and common forms of hearing impairment in the human population.

Functional and structural aspects of tinnitus-related enhancement and suppression of auditory cortex activity.

The steady-state auditory evoked magnetic field was recorded in tinnitus patients and controls, both either musicians or non-musicians, all of them with high-frequency hearing loss. Stimuli were AM-tones with two modulation frequencies and three carrier frequencies matching the "audiometric edge", i.e. the frequency above which hearing loss increases more rapidly, the tinnitus frequency or the frequency 1 1/2 octaves above the audiometric edge in controls, and a frequency 1 1/2 octaves below the audiometric edge. Stimuli equated in carrier frequency, but differing in modulation frequency, were simultaneously presented to the two ears. The modulation frequency-specific components of the dual steady-state response were recovered by bandpass filtering. In both hemispheres, the source amplitude of the response was larger for contralateral than ipsilateral input. In non-musicians with tinnitus, this laterality effect was enhanced in the hemisphere contralateral and reduced in the hemisphere ipsilateral to the tinnitus ear, especially for the tinnitus frequency. The hemisphere-by-input laterality dominance effect was smaller in musicians than in non-musicians. In both patient groups, source amplitude change over time, i.e. amplitude slope, was increasing with tonal frequency for contralateral input and decreasing for ipsilateral input. However, slope was smaller for musicians than non-musicians. In patients, source amplitude was negatively correlated with the MRI-determined volume of the medial partition of Heschl's gyrus. Tinnitus patients show an altered excitatory-inhibitory balance reflecting the downregulation of inhibition and resulting in a steeper dominance hierarchy among simultaneous processes in auditory cortex. Direction and extent of this alteration are modulated by musicality and auditory cortex volume.

Age-related auditory pathology in the CBA/J mouse.

Commercially obtained aged male CBA/J mice presented a complex pattern of hearing loss and morphological changes. A significant threshold shift in auditory brainstem responses (ABR) occurred at 3 months of age at 4 kHz without apparent loss of hair cells, rising slowly at later ages accompanied by loss of apical hair cells. A delayed high-frequency deficit started at 24 kHz around the age of 12 months. At 20-26 months, threshold shifts at 12 and 24 kHz and the accompanying hair cell loss at the base of the cochlea were highly variable with some animals appearing almost normal and others showing large deficits. Spiral ganglion cells degenerated by 18 months in all regions of the cochlea, with cell density reduced by approximately 25%. There was no degeneration of the stria vascularis and the endocochlear potential remained stable from 3 to 25 months of age regardless of whether the animals had normal or highly elevated ABR thresholds. The slow high-frequency hearing loss combined with a modest reduction of ganglion cell density and an unchanged endocochlear potential suggest sensorineural presbycusis. The superimposed early hearing loss at low frequencies, which is not seen in animals bred in-house, may complicate the use of these animals as a presbycusis model.

Saccular damage in patients with high-frequency sensorineural hearing loss.

Subjects with high frequency sensorineural hearing loss (HF-SNHL) without retrocochlear pathology are those group which certainly encountered inner ear damaging factors. This study was designed to evaluate the effects of cochlear damaging factors on the sacculocollic pathway. Fifty patients (76 ears) with varying degrees of HF-SNHL but without clinical manifestations of vestibular pathology tested for vestibular evoked myogenic potentials (VEMP). The results were compared with those of 18-healthy referents (32 ears) examined in the same way. Subjects with HF-SNHL greater than 40 dB HL showed significantly more saccular deterioration, estimated as negative VEMP responses than did the referents. This suggests subclinical disturbances of the vestibular system especially of the saccule in these patients. The underlying mechanism may be simultaneous damage to both the cochlea and saccule by the same factors.

Benefits of audibility for listeners with severe high-frequency hearing loss.

A consonant identification test was carried out with 10 hearing-impaired listeners under various low-pass filter conditions. Subjects were also tested for cochlear dead regions with the TEN test. All subjects had moderate-to-severe high-frequency hearing losses. Consonant recognition was tested under conditions in which the speech signals were highly audible to subjects for frequencies up to the low-pass filter cut-off. Extensive dead regions were found for one subject with the TEN test. The remaining subjects may have had dead regions above 3 kHz, because of the severity of their hearing losses, but these could not be demonstrated with the TEN test. Average consonant scores for the subject group improved significantly (p<0.05) with increasing audibility of high-frequency components of the speech signal. There were no cases of speech perception being reduced with increasing bandwidth. Nine of the subjects showed improvements in scores with increasing audibility, whereas the remaining subject showed little change in scores. For this subject, speech perception results were consistent with the TEN test findings. In general, the results suggest that listeners with severe high-frequency losses are often able to make some use of high-frequency speech cues if these cues can be made audible.

Factors affecting psychophysical tuning curves for hearing-impaired subjects with high-frequency dead regions.

A dead region (DR) is a region of the cochlea where there are no functioning inner hair cells and/or neurons. DRs can be detected using the threshold-equalizing-noise (TEN) test, but psychophysical tuning curves (PTCs) are sometimes used to give a more precise estimate of the edge frequency of a DR; a shifted tip of the PTC indicates a DR. We show here that the shapes of PTCs for hearing-impaired subjects can be influenced by the detection of beats and simple difference tones (SDTs). As a result, PTCs can have tips at f(s), even when f(s) falls in a DR. PTCs were measured for subjects with mild to moderate low-frequency and severe high-frequency hearing loss using sinusoidal and narrowband noise maskers (80-, 160-, 320-Hz wide): (1) in quiet; (2) in the presence of additional lowpass filtered noise (LF noise) designed to mask SDTs; (3) in the presence of a pair of low-frequency tones designed to interfere with the detection of beats (MDI tones). In condition (1), the PTCs were often W-shaped, with a sharp tip at f(s). This occurred less for the wider noise bandwidths. For subjects with good low-frequency hearing, the LF noise often reduced or eliminated the tip at f(s), suggesting that this tip was partly caused by detection of SDTs. For the sinusoidal and 80-Hz wide noise maskers, the addition of the MDI tones reduced the masker level required for threshold for masker frequencies adjacent to f(s), for nearly all subjects, suggesting a strong influence of beat detection. To minimize the influence of beats, we recommend using noise maskers with a bandwidth of 160 or (preferably) 320 Hz. In cases of near-normal hearing at low frequencies, we recommend using an additional LF noise to mask SDTs.

Hearing threshold elevation precedes hair-cell loss in prestin knockout mice.

Our previous characterization of prestin knockout (-/-) mice demonstrated that prestin is required for the eletromotility of outer hair cells (OHCs) and for the cochlear amplifier. Because hair-cell loss was observed in the basal 25% of cochleae in adult prestin-/- mice, it remained unclear how hair-cell loss progressed, whether hearing thresholds were elevated, and whether OHCs had normal ultra-structure in young prestin-/- mice. We report here that in prestin-/- mice, no significant hair-cell loss occurred before postnatal day 28 (P28); apoptosis of hair cells began at P28; and the loss of inner hair cells lagged behind that of OHCs. The prestin-/- mice had hearing thresholds that were significantly elevated (by approximately 25 dB) as early as P14; their thresholds at high frequencies were significantly elevated (by approximately 50 dB) at P21. The prestin heterozygous (+/-) mice displayed a significant threshold elevation (approximately 3.5 dB) at P21. In addition, transmission electronic microscopy shown that no obvious abnormality occurs in the sterocilla, lateral wall, tight junction and synapses of the outer hair cells. Our results demonstrate that the absence of prestin, not hair-cell loss, is the primary cause of high-frequency hearing threshold elevation in prestin-/- and +/- mice.

Enhanced frequency discrimination near the hearing loss cut-off: a consequence of central auditory plasticity induced by cochlear damage?

Patients with steeply sloping hearing losses of cochlear origin may exhibit enhanced difference limens for frequency (DLFs) near the cut-off frequency (Fc) of their hearing loss. This effect has been related to observations in deafened animals of an over-representation of Fc in the primary auditory cortex. However, alternative interpretations in terms of peripheral mechanisms have not been eliminated. In the present study, we assessed the possible role of two peripheral mechanisms [loudness cues and spontaneous otoacoustic emissions (SOAEs)] in a group of patients with high-frequency hearing loss. We tested first whether the DLF enhancement effect was still observed under conditions where subjects could not rely on loudness cues to perform the frequency discrimination task. To achieve this, we adjusted the nominal level of each stimulus so that it fell on an equal loudness contour measured at very fine (1/8 octave) frequency intervals, and we roved the level of each stimulus over a large range (12 dB). Under these conditions, the DLF enhancement was still observed in all patients; this demonstrates that the effect cannot be explained simply by loudness cues. We then screened the patients for SOAEs to test whether the DLF enhancement effect could be explained by the presence of such emissions in the vicinity of the Fc. None of the patients exhibited SOAEs. Finally, we tested whether the patients had cochlear dead regions, i.e. regions lacking functional inner hair cells and/or auditory nerve fibres. Using a refined version of a non-invasive clinical test for the identification of dead regions, we assessed the presence of such regions in fine frequency steps (1/4 octave) up to very high frequencies. All of the patients had cochlear dead regions. The first two findings support the hypothesis that DLF enhancement is due to injury-induced central reorganization in the auditory system. The last one is consistent with neurophysiological data in animals, which suggest that complete deprivation from auditory input at certain cochlear sites may be a necessary condition for the occurrence of injury-induced cortical reorganization.

Correlation between hearing loss and scala media area in guinea pigs with long-standing endolymphatic hydrops.

HYPOTHESIS: Histologic analysis of the hydropic and normal guinea pig cochleae was undertaken to assess a potential correlation between the magnitude of endolymphatic hydrops and hearing loss. It was hypothesized that a greater correlation than previously reported might be found by looking at long-standing endolymphatic hydrops and high-frequency range hearing. BACKGROUND: Surgically induced endolymphatic hydrops in guinea pigs is the most widely used animal model for the study of human Ménière's Disease and recapitulates both endolymphatic hydrops and progressive sensorineural hearing loss. A strong correlation between the magnitude of hydrops and severity of hearing loss has been reported in the human condition, but not in the animal model. METHODS: Nine albino guinea pigs were each subjected to surgical obstruction of the endolymphatic sac and duct of the right ear. The left ears remained as internal histologic controls. Hearing was assessed from 2 kHz to 32 kHz by auditory brain stem response testing for 16 to 25 weeks after surgery. Histologic morphometry after the animals were killed was used to quantify both turn-specific and weighted overall hydrops. These measures were correlated with hearing loss in each animal at all tested frequencies. RESULTS: A statistically significant correlation between the magnitude of hydrops and the severity of hearing loss was observed for 2 kHz and 16 kHz. These frequencies correlated with both turn-specific hydrops and overall hydrops. However, turn-specific hydrops did not reliably correlate with the magnitude of hearing loss at anatomically appropriate frequency ranges. Where such a correlation did exist, it might well have been simply part of an expression of an overall correlation between hydrops and hearing loss. CONCLUSIONS: There may be a greater correlation between hydrops and hearing loss in guinea pigs with long-standing surgically induced hydrops than has previously been reported in animals with less advanced disease. These findings help to validate continued use of the model for hearing loss related to Ménière's Disease, verify the rationale of treatment modalities aimed at reducing hydrops in the human condition, and may indicate that efforts at reducing hydrops in such patients has benefits toward long-term hearing preservation.

Nucleus magnocellularis and nucleus laminaris in Belgian Waterslager and normal strain canaries.

Belgian Waterslager (BWS) canaries are characterized by a mean 30% loss of hair cells in the basilar papilla compared to other canaries, and a corresponding increase in behavioral auditory thresholds. In spite of the large number of missing and damaged sensory cells, there is on average only a 12% reduction in the number of fibers in the VIIIth nerve. In this study, we examined cell number and size, and volume of auditory nuclei, specifically in nucleus magnocellularis and nucleus laminaris in Belgian Waterslager canaries. While the overall anatomical structure and organization of these nuclei and the total number of cells in the non-BWS and BWS canaries were comparable, BWS canaries showed a significant decrease in the volume of the auditory nuclei that was attributed to a reduction in cell size. These results provide further evidence in favor of a role of the sensory epithelium in the maintenance of central auditory structures.