Search

Cochlear synaptopathy is the noise-induced or age-related loss of ribbon synapses between inner hair cells (IHCs) and auditory-nerve fibers (ANFs), first reported in CBA/CaJ mice. Recordings from single ANFs in anesthetized, noise-exposed guinea pigs suggested that neurons with low spontaneous rates (SRs) and high thresholds are more vulnerable than low-threshold, high-SR fibers. However, there is extensive postexposure regeneration of ANFs in guinea pigs but not in mice. Here, we exposed CBA/CaJ mice to octave-band noise and recorded sound-evoked and spontaneous activity from single ANFs at least 2 wk later. Confocal analysis of cochleae immunostained for pre- and postsynaptic markers confirmed the expected loss of 40%-50% of ANF synapses in the basal half of the cochlea; however, our data were not consistent with a selective loss of low-SR fibers. Rather they suggested a loss of both SR groups in synaptopathic regions. Single-fiber thresholds and frequency tuning recovered to pre-exposure levels; however, response to tone bursts showed increased peak and steady-state firing rates, as well as decreased jitter in first-spike latencies. This apparent gain-of-function increased the robustness of tone-burst responses in the presence of continuous masking noise. This study suggests that the nature of noise-induced synaptic damage varies between different species and that, in mouse, the noise-induced hyperexcitability seen in central auditory circuits is also observed at the level of the auditory nerve. NEW & NOTEWORTHY Noise-induced damage to synapses between inner hair cells and auditory-nerve fibers (ANFs) can occur without permanent hair cell damage, resulting in pathophysiology that "hides" behind normal thresholds. Prior single-fiber neurophysiology in guinea pig suggested that noise selectively targets high-threshold ANFs. Here, we show that the lingering pathophysiology differs in mouse, with both ANF groups affected and a paradoxical gain-of-function in surviving low-threshold fibers, including increased onset rate, decreased onset jitter, and reduced maskability.

Background: Essential tremor (ET) is the most common adult movement disorder, characterized by several motor and increasingly well recognized non-motor symptoms. Sensory deficits, such as hearing impairment and olfactory dysfunction, are amongst them. This review analyzes the available evidence of these sensory deficits and their possible mechanistic basis in patients with ET., Method: A PubMed literature search on the topic was performed in the May 2019 database., Results: Nineteen articles on hearing impairment and olfactory dysfunction in ET patients were identified. The prevalence of hearing impairment is higher in ET patients than healthy controls or Parkinson disease. Cochlear pathologies are suggested as the underlying cause, but there is still a lack of information about retrocochlear pathologies and central auditory processing. Reports on olfactory dysfunction have conflicting results. The presence of mild olfactory dysfunction in ET was suggested. Conflicting results may be due to the lack of consideration of the disease's heterogeneity, but according to recent data, most studies do not find prominent evidence of olfactory loss in ET., Conclusion: Although there is increasing interest in studies on non-motor symptoms in ET, there are few studies on sensory deficits, which are of particularly high prevalence. More studies are needed on to investigate the basis of non-motor symptoms, including sensory deficits., Competing Interests: The author has no competing interests to declare., (Copyright: © 2020 The Author(s).)

Objective: The aging model of guinea pigs induced by D-galactose was set up to investigate the changes of BK(Ca) expression and function on cochlear pericytes and their relationship with age-related hearing loss. Methods: Thirty healthy 8-week-old guinea pigs were randomly divided into three groups, with 10 in each group: D-galactose aging model group, subcutaneous injection of D-galactose (500 mg/kg) daily for 6 weeks; saline control group, the same amount of saline was injected into the neck of the aging model group for 6 weeks; the blank control group, no treatment was performed. The threshold of auditory brainstem response (ABR) was detected. The content of BK(Ca) in the perivascular cells of the guinea pig cochlear cells was detected by immunofluorescence technique. The changes of peripheral current density and BK(Ca) current were detected by patch clamp technique. The data were analyzed by GraphPad Prism software. Results: Compared with the saline group and the control group, the ABR threshold and the amplitude of the wave I were significantly decreased in the aging model group, and the difference was statistically significant ( P< 0.01). Compared with the control group, the expression of BK(Ca) in the vascular pericytes of guinea pigs in the aging model group was significantly reduced (1.00±0.08 vs 0.27 ±0.03,the difference was statistically significant P< 0.01), and the cell current density and BK(Ca) net current value were also significantly reduced with statistically significant ( P <0.01). Conclusions: D-galactose can successfully induce guinea pig aging model, in which BK(Ca) expression decreases and net current value decreases in pericytes of cochlear striavascularis, and changes in BK(Ca) expression and function may be related to age-related hearing loss.

A 67-year-old woman was referred to the otolaryngology service after presenting to the emergency department for dizziness and loss of balance. She reported several similar episodes over the past years. Physical examination was unremarkable. A temporal bone CT scan revealed dehiscence between the bony carotid canal and the cochlea resulting in the diagnosis of carotid-cochlear dehiscence (CCD). CCD is an extremely rare condition involving the thinning of the bony canal separating the internal carotid artery from the cochlea. CCD is best diagnosed with temporal bone CT scan. Treatment options include observation as well as chemical or surgical labyrenthectomy. Despite similar clinical and diagnostic characteristics of reported CCD cases, general trends and consensus on treatment options cannot be ascertained due to the extreme rarity of this condition. Regardless of these limitations, CCD is a critical diagnosis as it mimics other inner ear conditions and poses a potential, significant surgical risk for the otolaryngologist., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The investigation of amplitudes of otoacoustic emissions in congenital hypothyroidism can provide information on cochlear function with more sensibility, when compared to other methods of auditory evaluation., Aim: To investigate cochlear function through the amplitude of distortion product otoacoustic emissions in individuals with congenital hypothyroidism and to correlate with clinical aspects., Methods: An exploratory, analytical, cross-sectional study with a convenience sample, composed of 50 individuals with congenital hypothyroidism and a group of 42 individuals without the disease, mean age of 8.4 (±3.1) years. The subjects of the research were evaluated by means of tonal and speech audiometry, immittance and distortion product otoacoustic emissions (DPOAEs). Continuous variables were described as mean or median and standard deviation. The Spearman test evaluated the correlations between the variables., Results: Otoacoustic emission amplitudes were significantly reduced in the exposed group, with congenital hypothyroidism, when compared to the group of individuals without the disease, especially in the medium frequencies. The Spearman test showed a slight correlation between the amplitude values of the otoacoustic emissions of some frequencies and the variables: disease time, diagnostic age, irregular serum free thyroxine hormone levels and thyroid stimulating hormone, especially in the condition of less treatment, whose correlation was negative., Conclusion: There was a correlation between the levels of signal amplitudes of otoacoustic emissions with clinical conditions and hormonal follow-up, suggesting probable subclinical auditory impairment in this population, as well as influence of some clinical aspects of congenital hypothyroidism on auditory function., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hearing impairment is the most common sensory deficit, affecting more than 400 million people worldwide. Sensorineural hearing losses currently lack any specific or efficient pharmacotherapy largely due to the insufficient knowledge of the pathomechanism. Purinergic signaling plays a substantial role in cochlear (patho)physiology. P2 (ionotropic P2X and the metabotropic P2Y) as well as adenosine receptors expressed on cochlear sensory and non-sensory cells are involved mostly in protective mechanisms of the cochlea. They are implicated in the sensitivity adjustment of the receptor cells by a K + shunt and can attenuate the cochlear amplification by modifying cochlear micromechanics. Cochlear blood flow is also regulated by purines. Here, we propose to comprehend this field with the purine-immune interactions in the cochlea. The role of harmful immune mechanisms in sensorineural hearing losses has been emerging in the horizon of cochlear pathologies. In addition to decreasing hearing sensitivity and increasing cochlear blood supply, influencing the immune system can be the additional avenue for pharmacological targeting of purinergic signaling in the cochlea. Elucidating this complexity of purinergic effects on cochlear functions is necessary and it can result in development of new therapeutic approaches in hearing disabilities, especially in the noise-induced ones.

Animal studies demonstrate that noise exposure can permanently damage the synapses between inner hair cells and auditory nerve fibers, even when outer hair cells are intact and there is no clinically relevant permanent threshold shift. Synaptopathy disrupts the afferent connection between the cochlea and the central auditory system and is predicted to impair speech understanding in noisy environments and potentially result in tinnitus and/or hyperacusis. While cochlear synaptopathy has been demonstrated in numerous experimental animal models, synaptopathy can only be confirmed through post-mortem temporal bone analysis, making it difficult to study in living humans. A variety of non-invasive measures have been used to determine whether noise-induced synaptopathy occurs in humans, but the results are conflicting. The overall objective of this article is to synthesize the existing data on the functional impact of noise-induced synaptopathy in the human auditory system. The first section of the article summarizes the studies that provide evidence for and against noise-induced synaptopathy in humans. The second section offers potential explanations for the differing results between studies. The final section outlines suggested methodologies for diagnosing synaptopathy in humans with the aim of improving consistency across studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study aims to find an effective chirp signal that enhances the amplitude of wave-I of auditory brainstem response (ABR) to diagnose "cochlear synaptopathy." Although several chirp signals have been proposed to enhance the amplitude of wave-V, the effect on wave-I has not been clarified yet. Ten chirp signals, which have shorter group delays than the commonly used "CE-chirp," were produced to measure the amplitudes of wave-I and wave-V of the ABRs. The results show that one of the chirp signals significantly enhanced the amplitude of wave-I, where the group delay is approximately half of the CE-chirp., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Investigations of cochlear synaptopathy in living humans rely on proxy measures of auditory nerve function. Numerous procedures have been developed, typically based on the auditory brainstem response (ABR), envelope-following response (EFR), or middle-ear-muscle reflex (MEMR). Validation is challenging, due to the absence of a gold-standard measure in humans. Some metrics correlate with synaptic survival in animal models, but translation between species is not straightforward; measurements in humans are likely to reflect greater error and greater variability from non-synaptopathic sources. The present study assessed the reliability of seven measures, as well as testing for correlations between them. Thirty-one young women with normal audiograms underwent repeated measurements of ABR wave I amplitude, ABR wave I growth, ABR wave V latency shift in noise, EFR amplitude, EFR growth with stimulus modulation depth, MEMR threshold, and an MEMR across-frequency difference measure. Intraclass correlation coefficients for ABR wave I amplitude, EFR amplitude, and MEMR threshold ranged from 0.85 to 0.93, suggesting that such tests can yield highly reliable results, given careful measurement techniques. The ABR and EFR difference measures exhibited only poor-to-moderate reliability. No significant correlations, nor any consistent trends, were observed between the various measures, providing no indication that these metrics reflect the same underlying physiological processes. Findings suggest that many proxy measures of cochlear synaptopathy should be regarded with caution, at least when employed in young adults with normal audiograms., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Waardenburg syndrome (WS) is the consequence of an inherited autosomal dominant mutation which causes the early degeneration of intermediate cells of cochlear stria vascularis (SV) and profound hearing loss. Patients with WS may also experience primary vestibular symptoms. Most of the current WS studies did not discuss the relationship between WS and abnormal vestibular function. Our study found that a spontaneous mutant pig showed profound hearing loss and depigmentation. MITF-M, a common gene mutation causes type WS which affect the development of the intermediate cell of SV, was then identified for animal modeling., Results: In this study, the degeneration of vestibular hair cells was found in pigs with MITF-M. The morphology of hair cells in vestibular organs of pigs was examined using electron microscopy from embryonic day E70 to postnatal two weeks. Significant hair cell loss in the mutant saccule was found in this study through E95 to P14. Conversely, there was no hair cell loss in either utricle or semi-circular canals., Conclusions: Our study suggested that MITF-M gene mutation only affects hair cells of the saccule, but has no effect on other vestibular organs. The study also indicated that the survival of cochlear and saccular hair cells was dependent on the potassium release from the cochlear SV, but hair cells of the utricle and semi-circular canals were independent on SV.

Introduction: Individuals with persistent symptoms after mild traumatic brain injury (mTBI) often have auditory complaints. In this study, we used the auditory brainstem response (ABR) to determine whether cochlear synaptopathy could explain auditory symptoms., Methods: 69 adult military service members with mTBI and 25 adults without brain injury (NCT01611194 and NCT01925963) completed pure-tone audiometry, ABR, and central auditory processing tests. All participants were male, ages 21-50., Results: 37/69 mTBI participants had measurable hearing loss, while another 20%-30% had hearing complaints or tinnitus. While mTBI participants with measurable hearing loss had reduced wave I and III amplitude and decreased III-V interpeak latency, those with no measurable hearing loss did not significantly differ from controls on any ABR parameter. Those with measurable hearing loss were also more likely to have abnormal central auditory processing. mTBI participants with no measurable hearing loss but who reported hearing concerns had some ABR findings (III-V interpeak latency, I and V amplitudes, V/I amplitude ratio) more like the measurable hearing loss mTBI group than normative controls., Conclusion: Cochlear synaptopathy may have contributed to some of the auditory impairment in service members with mTBI with measurable hearing loss. However, these results are likely confounded by cochlear hair cell damage., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

Cisplatin is a potent chemotherapeutic compound for which ototoxicity is a significant side effect. Cisplatin has shown sensitivity to circadian time, in that cisplatin is most effective as an anti-tumor compound, and least nephrotoxic, when given in the active (dark) period of the light-dark cycle in rodents. The objective of the study was to determine the sensitivity of cisplatin ototoxicity to circadian time. Fifty-seven Fischer 344/NHsd rats were exposed to 12 mg/kg cisplatin by intra-peritoneal injection at one of six time points on a 12 h light-12 h dark cycle: 2, 6, or 10 h after light onset or 2, 6, or 10 h after light offset. Cochlear injury was evaluated using auditory brainstem response threshold shifts and postmortem outer hair cell counts. All animals experienced threshold shift in the highest frequencies tested (30 and 40 kHz). The animals exposed to cisplatin at 6 h after light onset (the inactive period) had significantly higher mid-frequency threshold shifts and outer hair cell losses than the groups exposed during the dark hours. The results indicate that cisplatin is less likely to cause ototoxicity in the Fischer 344/NHsd rat when given during the active period. This finding is consistent with the lower nephrotoxicity that has been detected in cisplatin-exposed animals treated during the dark hours, and the magnitude of differences in threshold shifts between the light and dark exposure indicates that circadian timing has a significant impact on susceptibility to cisplatin ototoxicity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cochlear synaptopathy, the loss of synaptic connections between inner hair cells (IHCs) and auditory nerve fibers, has been documented in animal models of aging, noise, and ototoxic drug exposure, three common causes of acquired sensorineural hearing loss in humans. In each of these models, synaptopathy begins prior to changes in threshold sensitivity or loss of hair cells; thus, this underlying injury can be hidden behind a normal threshold audiogram. Since cochlear synaptic loss cannot be directly confirmed in living humans, non-invasive assays will be required for diagnosis. In animals with normal auditory thresholds, the amplitude of wave 1 of the auditory brainstem response (ABR) is highly correlated with synapse counts. However, synaptopathy can also co-occur with threshold elevation, complicating the use of the ABR alone as a diagnostic measure. Using an age-graded series of mice and a partial least squares regression approach to model structure-function relationships, this study shows that the combination of a small number of ABR and distortion product otoacoustic emission (DPOAE) measurements can predict synaptic ribbon counts at various cochlear frequencies to within 1-2 synapses per IHC of their true value. In contrast, the model, trained using the age-graded series of mice, overpredicted synapse counts in a small sample of young noise-exposed mice, perhaps due to differences in the underlying pattern of damage between aging and noise-exposed mice. These results provide partial validation of a noninvasive approach to identify synaptic/neuronal loss in humans using ABRs and DPOAEs., (Published by Elsevier B.V.)

There is a growing interest in the auditory community to develop novel prophylactic and therapeutic drugs to prevent permanent sensorineural hearing loss following acute cochlear injury. The jun-N-terminal protein kinase (JNK) pathway plays a crucial role in acute sensory hearing loss. Blocking the JNK pathway using the cell-penetrating peptide D-JNKI-1 (AM-111/brimapitide) has shown promise as both a prophylactic and therapeutic agent for acute cochlear injury. A number of pre-clinical and clinical studies have determined the impact of D-JNKI-1 on acute sensorineural hearing loss. Given the inner-ear selective therapeutic profile, local route of administration, and ability to diffuse across cellular membranes rapidly using both active and passive transport makes D-JNK-1 a promising oto-protective drug. In this review article, we discuss the application of D-JNKI-1 in various auditory disorders as well as its pharmacological properties and distribution in the cochlea., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Recent animal studies have shown that the synapses between inner hair cells and the dendrites of the spiral ganglion cells they innervate are the elements in the cochlea most vulnerable to excessive noise exposure. Particularly in rodents, several studies have concluded that exposure to high level octave-band noise for 2 h leads to an irreversible loss of around 50% of synaptic ribbons, leaving audiometric hearing thresholds unaltered. Cochlear synaptopathy following noise exposure is hypothesized to degrade the neural encoding of sounds at the subcortical level, which would help explain certain listening-in-noise difficulties reported by some subjects with otherwise 'normal' hearing. In response to this peripheral damage, increased gain of central stages of the auditory system has been observed across several species of mammals, particularly in association with tinnitus. The auditory brainstem response (ABR) wave I amplitude and waves I-V amplitude ratio have been suggested as non-invasive indicators of cochlear synaptopathy and central gain activation respectively, but the evidence for these hearing disorders in humans is inconclusive. In this study, we evaluated the influence of lifetime noise exposure (LNE) on the human ABR and on speech-in-noise intelligibility performance in a large cohort of adults aged 29 to 55. Despite large inter-subject variability, results showed a moderate, but statistically significant, negative correlation between the ABR wave I amplitude and LNE, consistent with cochlear synaptopathy. The results also showed (a) that central gain mechanisms observed in animal studies might also occur in humans, in which higher stages of the auditory pathway appear to compensate for reduced input from the cochlea; (b) that tinnitus was associated with activation of central gain mechanisms; (c) that relevant cognitive and subcortical factors influence speech-in-noise intelligibility, in particular, longer ABR waves I-V interpeak latencies were associated with poorer performance in understanding speech in noise when central gain mechanisms were active; and (d) absence of a significant relationship between LNE and tinnitus, central gain activation or speech-in-noise performance. Although this study supports the possible existence of cochlear synaptopathy in humans, the great degree of variability, the lack of uniformity in central gain activation and the significant involvement of attention in speech-in-noise performance suggests that noise-induced cochlear synaptopathy is, at most, one of several factors that play a role in humans' speech-in-noise performance., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Cochlear synaptopathy, i.e. the loss of auditory-nerve connections with cochlear hair cells, is seen in aging, noise damage, and other types of acquired sensorineural hearing loss. Because the subset of auditory-nerve fibers with high thresholds and low spontaneous rates (SRs) is disproportionately affected, audiometric thresholds are relatively insensitive to this primary neural degeneration. Although suprathreshold amplitudes of wave I of the auditory brainstem response (ABR) are attenuated in synaptopathic mice, there is not yet a robust diagnostic in humans. The middle-ear muscle reflex (MEMR) might be a sensitive metric (Valero et al., 2016), because low-SR fibers may be important drivers of the MEMR (Liberman and Kiang, 1984; Kobler et al., 1992). Here, to test the hypothesis that narrowband reflex elicitors can identify synaptopathic cochlear regions, we measured reflex growth functions in unanesthetized mice with varying degrees of noise-induced synaptopathy and in unexposed controls. To separate effects of the MEMR from those of the medial olivocochlear reflex, the other sound-evoked cochlear feedback loop, we used a mutant mouse strain with deletion of the acetylcholine receptor required for olivocochlear function. We demonstrate that the MEMR is normal when activated from non-synaptopathic cochlear regions, is greatly weakened in synaptopathic regions, and is a more sensitive indicator of moderate synaptopathy than the suprathreshold amplitude of ABR wave I., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Traumatic noise causes hearing loss by damaging sensory hair cells and their auditory synapses. There are no treatments. Here, we investigated mice exposed to a blast wave approximating a roadside bomb. In vivo cochlear imaging revealed an increase in the volume of endolymph, the fluid within scala media, termed endolymphatic hydrops. Endolymphatic hydrops, hair cell loss, and cochlear synaptopathy were initiated by trauma to the mechanosensitive hair cell stereocilia and were K + -dependent. Increasing the osmolality of the adjacent perilymph treated endolymphatic hydrops and prevented synaptopathy, but did not prevent hair cell loss. Conversely, inducing endolymphatic hydrops in control mice by lowering perilymph osmolality caused cochlear synaptopathy that was glutamate-dependent, but did not cause hair cell loss. Thus, endolymphatic hydrops is a surrogate marker for synaptic bouton swelling after hair cells release excitotoxic levels of glutamate. Because osmotic stabilization prevents neural damage, it is a potential treatment to reduce hearing loss after noise exposure., Competing Interests: The authors declare no conflict of interest.

Purpose: The purpose of this study is to investigate the association between obstructive sleep apnea (OSA) with middle ear acoustic transference and cochlear function., Methods: Male individuals with and without mild, moderate, and severe OSA according to standard criteria of full polysomnography and no co-morbidities were studied. Subjects with BMI ≥40 kg/m 2 , present or past treatment for OSA, with heart failure, diabetes, hypertension, dyslipidemia, stroke, use of chronic medications, and previous history of risk for hearing loss were excluded. All subjects were submitted to full polysomnography, evaluation of wideband acoustic immittance by energy of absorbance (EA), and distortion product otoacoustic emissions (DPOAE)., Results: We studied 38 subjects (age 35.8 ± 7.2 years, BMI 28.8 ± 3.8 kg/m 2 ) divided into no OSA (n = 10, age 33.6 ± 6.4 years, BMI 26.9 ± 4.1 kg/m 2 ), mild (n = 11, age 32.8 ± 2.9 years, BMI 28.5 ± 3.5 kg/m 2 ), moderate (n = 8, age 34.1 ± 6.8 years, BMI 29.6 ± 3.3 kg/m 2 ), and severe OSA (n = 9, age 41.2 ± 9.2 years, BMI 30.5 ± 3.8 kg/m 2 ). EA was similar between groups. In contrast, patients with severe OSA presented significantly lower DPOAE amplitudes when compared to the control, mild, and moderate OSA groups (p ≤ 0.03, for all comparisons)., Conclusions: Acoustic transference function of middle ear is similar in adults with and without OSA. Severe OSA is independently associated with cochlear function impairment in patients with no significant co-morbidities.

Objective: The aim of the current study is to evaluate audiologic and radiologic findings of cochlear hypoplasia which is a subgroup of inner ear malformations., Methods: This study was a prospective clinical study and based on voluntary participation from cases with cochlear hypoplasia diagnosis. The study was conducted at Hacettepe University, Department of Otolaryngology, Head and Neck Surgery and Department of Audiology. Subjects were selected from an inner ear malformations database. Inclusion criteria were having cochlear hypoplasia for at least one ear. There were 66 subjects with an age range of 12 months and 60 years 5 months. For each subject, pure tone audiometry and tympanometry were applied according to chronological and cognitive age. And also, auditory brainstem response test was applied to when it is need. Subjects' radiologic results were reevaluated to confirm cochlear hypoplasia, cochlear nerve and cochlear aperture., Results: Cochlear hypoplasia types were statistically significantly different in terms of HL degree. This difference was caused by cochlear hypoplasia type IV group being was statistically different from the other three groups. Like with degree of HL, cochlear hypoplasia groups were statistically different from other three groups in terms of type of hearing loss. Cochlear aperture and cochlear nerve status showed variation according to cochlear hypoplasia type but these differences were not statistically approved., Conclusions: In the current study, incidence of cochlear hypoplasia was 23.5% in all inner ear malformation. With this study, it was seen that subtypes of cochlear hypoplasia showed variability in terms of degree and type of hearing loss and also cochlear aperture and cochlear nerve status. Especially cochlear hypoplasia type IV differs from other three cochlear hypoplasia types., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Cochlear synaptopathy can result from various insults, including acoustic trauma, aging, ototoxicity, or chronic conductive hearing loss. For example, moderate noise exposure in mice can destroy up to ∼50% of synapses between auditory nerve fibers (ANFs) and inner hair cells (IHCs) without affecting outer hair cells (OHCs) or thresholds, because the synaptopathy occurs first in high-threshold ANFs. However, the fiber loss likely impairs temporal processing and hearing-in-noise, a classic complaint of those with sensorineural hearing loss. Non-human primates appear to be less vulnerable to noise-induced hair-cell loss than rodents, but their susceptibility to synaptopathy has not been studied. Because establishing a non-human primate model may be important in the development of diagnostics and therapeutics, we examined cochlear innervation and the damaging effects of acoustic overexposure in young adult rhesus macaques. Anesthetized animals were exposed bilaterally to narrow-band noise centered at 2 kHz at various sound-pressure levels for 4 h. Cochlear function was assayed for up to 8 weeks following exposure via auditory brainstem responses (ABRs) and otoacoustic emissions (OAEs). A moderate loss of synaptic connections (mean of 12-27% in the basal half of the cochlea) followed temporary threshold shifts (TTS), despite minimal hair-cell loss. A dramatic loss of synapses (mean of 50-75% in the basal half of the cochlea) was seen on IHCs surviving noise exposures that produced permanent threshold shifts (PTS) and widespread hair-cell loss. Higher noise levels were required to produce PTS in macaques compared to rodents, suggesting that primates are less vulnerable to hair-cell loss. However, the phenomenon of noise-induced cochlear synaptopathy in primates is similar to that seen in rodents., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The objective of this study is to review the scientific literature to determine if a set of stimulus parameters can be described to elicit distortion product otoacoustic emissions (DPOAEs) of higher absolute level and/or greater reliability in healthy adult humans and higher sensitivity and specificity in adults with cochlear lesions., Design: Systematic review., Study Sample: Searches of four electronic databases yielded 47 studies that had used different parameters to elicit DPOAEs from within or between-groups of adult humans., Results: The wide range of stimulus parameters used in the reviewed studies saw a wide range of reported values for DPOAE level, reliability, and sensitivity and specificity to cochlear lesions., Conclusion: The most commonly used stimulus parameters for eliciting DPOAEs from adult humans have included frequency ratios for the two primary tones (f 2 /f 1 ) of between 1.04 and 1.4 and levels (L 1 /L 2 ) of 65/55 dB SPL. The most commonly used parameters for eliciting DPOAEs of higher level in healthy adults appear to be linked to f 2 /f 1 values between 1.20 and 1.22 and L 1 /L 2 levels of 75/75 dB SPL. The stimulus parameters for eliciting DPOAEs of greater reliability in healthy adults and higher sensitivity and specificity in adults with cochlear lesions have yet to be clearly determined.

There is substantial variability in speech recognition ability across patients with cochlear implants (CIs), auditory brainstem implants (ABIs), and auditory midbrain implants (AMIs). To better understand how this variability is related to central processing differences, the current electroencephalography (EEG) study compared hearing abilities and auditory-cortex activation in patients with electrical stimulation at different sites of the auditory pathway. Three different groups of patients with auditory implants (Hannover Medical School; ABI: n = 6, CI: n = 6; AMI: n = 2) performed a speeded response task and a speech recognition test with auditory, visual, and audio-visual stimuli. Behavioral performance and cortical processing of auditory and audio-visual stimuli were compared between groups. ABI and AMI patients showed prolonged response times on auditory and audio-visual stimuli compared with NH listeners and CI patients. This was confirmed by prolonged N1 latencies and reduced N1 amplitudes in ABI and AMI patients. However, patients with central auditory implants showed a remarkable gain in performance when visual and auditory input was combined, in both speech and non-speech conditions, which was reflected by a strong visual modulation of auditory-cortex activation in these individuals. In sum, the results suggest that the behavioral improvement for audio-visual conditions in central auditory implant patients is based on enhanced audio-visual interactions in the auditory cortex. Their findings may provide important implications for the optimization of electrical stimulation and rehabilitation strategies in patients with central auditory prostheses. Hum Brain Mapp 38:2206-2225, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

This article presents the data on the frequency, diagnostics, and variants of the surgical treatment of the fistula of the round window of the cochlea. A case of this pathology is reported with the special emphasis placed on the approaches to the diagnostics and surgical management of this condition.

The objective of the present study was the prospective analysis of the results of bilateral cochlear implantation (CI) in the children presenting with bilateral ossification of the cochlea after they had survived meningitis. A total of 15 patients underwent the surgical intervention. In those exhibiting bilateral ossification of the basal cochlear helix over the 5 mm segment (up to first bend of the cochlear turn) and partial ossification of the second helix (in 6 children), the affected portions were removed with the placement of two choleostomies, the lower one (from the ossified membrane of the cochlear window) and the upper one (toward the second helix). Activation of the speech processors of the CI systems was carried out within 4-6 weeks after surgery. The hearing abilities of the children were evaluated in accordance with the 'Estimation of the auditory perception categories', 'Estimation of the child's apprehension capacity', and 'Analysis of speech intelligibility rating' guidelines. In all the children with ossification over less than 5 mm of the basal cochlear helix, it proved possible to introduce the whole intracochlear electrode grid whereas only half of the electrode array was implanted in the cases of overall ossification of the basal helix. The first results obtained by telemetry and surdopedagogical testing gave evidence of the possibility of identifying various sources of non-verbal and speech stimuli in all the treated children at a small (up to 3 meters) distance.

Reduction of endocochlear potential (EP) is one of the main causes of sensorineural hearing loss. In this study, we investigated changes in the EP using a mouse model of acute cochlear energy failure, which comprised severe cochlear lateral wall damage induced by the local administration of 3-nitropropionic acid to the inner ear. We also analyzed the correlation between EP changes and histological findings in the cochlear lateral wall. We detected the recovery of the EP and hearing function at lower frequencies after severe damage of the cochlear lateral wall fibrocytes at the corresponding region. Remodeling of the cochlear lateral wall was associated with EP recovery, including the re-expression of ion transporters or gap junctions (i.e. Na/K/ATPase-β1 and connexin 26). These results indicate a mechanism for late-phase hearing recovery after severe deafness, which is frequently observed in clinical settings.

Objective: The angular vestibulo-ocular reflex (aVOR) is known to be influenced by factors such as arousal and cognition during traditional vestibular function testing. However, the inherent variability of the aVOR to head impulse testing has not been explicitly examined. The purpose of this study was to determine the variability of the aVOR to active and passive head impulses using the gold standard scleral search coil method to record head and eye rotation., Study Design: Descriptive., Setting: Tertiary referral center., Patients: Twenty six healthy control subjects agreed to active and passive horizontal head impulse testing on at least two separate sessions from two unique institutions. An additional 27 individuals with cochlear implantation (CI) underwent passive horizontal and vertical semicircular canal plane head impulse testing. Test sessions were separated from 3 to 210 days in the normal subjects and from 49 to 537 days in the subjects with CI., Main Outcome Measure(s): Reliability of the angular VOR gain (eye velocity/head velocity) over time., Results: In the healthy control subjects, there was no difference in aVOR gain between right and left ears, between session one and session two, or between active (self-generated, 0.99 ± 0.08) or passive (imposed, 1.0 ± 0.08) head impulses. In the patients, we also found the aVOR gain very stable over time. However, the aVOR gains of the patients were different across the semicircular canal planes tested (p < 0.001) with the four vertical semicircular canals having lower aVOR gains than the two horizontal canals., Conclusions: Our data suggest the aVOR gain is quite stable when tested across unique days in healthy controls and patients with auditory-only inner ear pathology.

Objectives/hypothesis: Pathologic third window lesions, such as superior semicircular canal dehiscence syndrome (SCDS) or large vestibular aqueduct syndrome (LVAS), cause several auditory and vestibular symptoms, which might affect perilymphatic pressure and induce endolymphatic hydrops (EH). In this study, the existence of EH in subjects with SCDS or LVAS was investigated using contrast-enhanced magnetic resonance imaging (MRI)., Study Design: Case series at university hospital., Methods: Seventeen ears from nine subjects who were diagnosed as having SCDS (five ears from three cases) or LVAS (12 ears from six cases) were studied. Ears were evaluated by 3-T MRI performed 4 hours after intravenous injection of gadodiamide hydrate. Imaging data concerning the degree of EH in the cochlea and the vestibule were compared with clinical symptoms and hearing levels for all ears., Results: All ears showed air-bone gaps at low frequencies on pure tone audiometry. None of the subjects with SCDS had episodes of acute sensorineural hearing loss (SNHL) or vestibular symptoms, except for one patient who complained of head vibration induced by loud noise. Conversely, five of six subjects with LVAS had episodes of acute SNHL or vestibular symptoms. Four of five ears with SCDS showed severe EH in the cochlea, and two ears showed mild EH in the vestibule. All ears with LVAS showed mild to severe EH in both the cochlea and vestibule., Conclusions: The present study demonstrated the existence of EH in ears with pathologic third window lesions, which might affect patients' auditory or vestibular symptoms., Level of Evidence: 4 Laryngoscope, 126:1446-1450, 2016., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) have distinct distributions in the cochlear nucleus that correspond to sources of the labeled terminals. VGLUT1 is mainly associated with terminals of auditory nerve fibers, whereas VGLUT2 is mainly associated with glutamatergic terminals deriving from other sources that project to the cochlear nucleus (CN), including somatosensory and vestibular terminals. Previous studies in guinea pig have shown that cochlear damage results in a decrease of VGLUT1-labeled puncta and an increase in VGLUT2-labeled puncta. This indicates cross-modal compensation that is of potential importance in somatic tinnitus. To examine whether this effect is consistent across species and to provide a background for future studies, using transgenesis, the current study examines VGLUT expression profiles upon cochlear insult by intracochlear kanamycin injections in the mouse. Intracochlear kanamycin injections abolished ipsilateral ABR responses in all animals and reduced ipsilateral spiral ganglion neuron densities in animals that were sacrificed after four weeks, but not in animals that were sacrificed after three weeks. In all unilaterally deafened animals, VGLUT1 density was decreased in CN regions that receive auditory nerve fiber terminals, i.e., in the deep layer of the dorsal cochlear nucleus (DCN), in the interstitial region where the auditory nerve enters the CN, and in the magnocellular region of the antero- and posteroventral CN. In contrast, density of VGLUT2 expression was upregulated in the fusiform cell layer of the DCN and in the granule cell lamina, which are known to receive somatosensory and vestibular terminals. These results show that a cochlear insult induces cross-modal compensation in the cochlear nucleus of the mouse, confirming previous findings in guinea pig, and that these changes are not dependent on the occurrence of spiral ganglion neuron degeneration., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

The objective of the present study was to develop the non-damaging method for the insertion of a standard electrode for cochlear ossification with a view to improving the results of hearing and speech rehabilitation of the patients presenting with grade IV sensorineural impairment of hearing. Twenty preparations of the cadaveric temporal bone were used to investigate topographic and anatomical relationships in the main structures of the middle and internal ears, viz. the second cochlear coil, vestibulum and its windows, processus cochleaformis, spiral lamina, and modiolus. The optimal method for the insertion of a standard electrode into the spiral canal of the cochlea after the removal of the ossified structures is proposed. The optimal site for constructing the second colostomy is determined that allows the spiral plate and modiolus to be maximally preserved. The proposed method was employed to treat 11 patients with grade IV sensorineural impairment of hearing and more than 5 mm ossification of the basal cochlear coil. With this method, it proved possible to insert the maximum number of electrodes into the cochlear spiral canal and thereby to obtain excellent results of hearing and speech rehabilitation in the patients with the ossified cochlea.

Objective: To present the first reported case of intraneural direct cochlear nerve stimulation in a human being., Study Design: This is a case report., Results: A 23-year-old patient with bilateral progressive hearing loss associated with bilateral complete semicircular canal aplasia and ossified cochleas underwent cochlear implantation. During surgery, a patent cochlear lumen could not be found, and the array was positioned in the internal auditory canal adjacent to the cochlear nerve. Against our expectations, an assiduous rehabilitation and frequent fitting adjustments have led to a word recognition score, in open set speech with lip reading, of 18/25 and acceptable frequency discrimination., Conclusions: We are aware that this was an anomalous use of the cochlear implant, and it is not our aim to suggest a new indication for cochlear array positioning. However, this case shows that auditory perception, to some degree, can be obtained with intraneural direct cochlear nerve stimulation., (© The Author(s) 2015.)

Objectives: The aim of this study was to focus on patients suffering from cochleo-vestibular disorder with and without Ménière disease (MD) in order to verify whether chronic cerebrospinal drainage abnormalities could play a role in the etiopathogenesis of endolymphatic hydrops., Methods: Fifty-two volunteers were enrolled and subdivided into two groups: 24 definite MD and 28 not-MD. Both magnetic resonance venography imaging with contrast-enhanced imaging of the venous cerebrospinal system (MRV) and venous echo-color Doppler (ECD) were performed., Results: MRV showed abnormalities in 83% of MD and 57% of not-MD subjects (p < 0.001). Asymmetrical cervical venous flow, assessed by MRV, was confirmed by ECD in 62.5% of MD but in only 21.5% of not-MD subjects (p<0.001)., Conclusion: Chronic cerebrospinal venous insufficiency might be the anatomical background, which provides a predisposing factor for the development of endolymphatic hydrops in MD patients., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Vitiligo has been classified clinically into segmental vitiligo (SV) and nonsegmental vitiligo (NSV) and may also be associated with audiological abnormalities., Objectives: We examined cochlear function in ears of individuals with SV and NSV, including subjects with facial and nonfacial lesions, and in patients who have SV with unilateral facial involvement., Methods: This study included 25 patients with SV and 28 patients with NSV. Fifteen age- and sex-matched healthy individuals served as controls. Cochlear function was studied using the distortion product otoacoustic emissions (DPOAEs). Data were analysed using SPSS., Results: Sixty-four ears (60%) of patients with vitiligo had cochlear dysfunction while the control group exhibited no abnormalities. On comparing the cochlear dysfunction of patients with SV with patients with NSV, no statistically significant difference was found. The ears on both sides, affected and unaffected by vitiligo, in patients with SV showed cochlear dysfunction with no statistically significant difference in DPOAE. To determine the effect of the lesion side on cochlear function, we compared DPOAE amplitude using Student's t-test. The comparisons included NSV of the face vs. NSV on other areas, NSV of the face vs. SV of the face and SV of the face vs. SV of other areas. No statistically significant difference was found in these comparisons., Conclusions: Bilateral cochlear dysfunction is common in both NSV and SV and does not reflect the appearance of vitiligo in the skin. Our results underscore the important role of melanocytes and melanin in cochlear function, and suggest that the cochlear abnormalities in SV point to the presence of additional nonsegmental pathophysiological events underlying all forms of vitiligo., (© 2014 British Association of Dermatologists.)

Background: Lyme disease is the most common vector-borne disease in the United States and is caused by infection with the spirochete Borrelia burgdorferi. In children, neuroborreliosis usually presents as peripheral facial nerve palsy and lymphocytic meningitis and only rarely is associated with cranial polyneuritis., Patient Description: We present a 15-year-old with tinnitus, hearing loss, and facial nerve palsy in the setting of acute, severe right arm pain and a several week history of malaise and headache. Lumbar puncture was notable for lymphocytic pleocytosis. Serologic testing demonstrated positive Lyme antibody and a positive immunoglobulin M Western blot. Immunofluorescent assay of cerebrospinal fluid was also positive for anti-Lyme immunoglobulin M. Audiologic testing revealed mixed, right-sided hearing loss. Neuroimaging demonstrated cranial polyneuritis and right-sided cochlear inflammation. The patient was treated with parenteral ceftriaxone with resolution of his symptoms at close follow-up., Discussion: Neuroborreliosis with radiculopathy, lymphocytic meningitis, and cranial polyneuritis is a rare presentation of pediatric Lyme disease. Additionally, cochlear inflammation along with cranial nerve VIII inflammation may contribute to hearing loss in patients with neuroborreliosis., (Published by Elsevier Inc.)

In the mammalian auditory system, the three rows of outer hair cells (OHCs) located in the cochlea are thought to increase the displacement amplitude of the organ of Corti. This cochlear amplification is thought to contribute to the high sensitivity, wide dynamic range, and sharp frequency selectivity of the hearing system. Recent studies have shown that traumatic stimuli, such as noise exposure and ototoxic acid, cause functional loss of OHCs in one, two, or all three rows. However, the degree of decrease in cochlear amplification caused by such functional losses remains unclear. In the present study, a finite element model of a cross section of the gerbil cochlea was constructed. Then, to determine effects of the functional losses of OHCs on the cochlear amplification, changes in the displacement amplitude of the basilar membrane (BM) due to the functional losses of OHCs were calculated. Results showed that the displacement amplitude of the BM decreases significantly when a single row of OHCs lost its function, suggesting that all three rows of OHCs are required for cochlear amplification.

Brain-derived neurotrophic factor, BDNF, is one of the most important neurotrophic factors acting in the peripheral and central nervous system. In the auditory system its function was initially defined by using constitutive knockout mouse mutants and shown to be essential for survival of neurons and afferent innervation of hair cells in the peripheral auditory system. Further examination of BDNF null mutants also revealed a more complex requirement during re-innervation processes involving the efferent system of the cochlea. Using adult mouse mutants defective in BDNF signaling, it could be shown that a tonotopical gradient of BDNF expression within cochlear neurons is required for maintenance of a specific spatial innervation pattern of outer hair cells and inner hair cells. Additionally, BDNF is required for maintenance of voltage-gated potassium channels (KV) in cochlear neurons, which may form part of a maturation step within the ascending auditory pathway with onset of hearing and might be essential for cortical acuity of sound-processing and experience-dependent plasticity. A presumptive harmful role of BDNF during acoustic trauma and consequences of a loss of cochlear BDNF during aging are discussed in the context of a partial reversion of this maturation step. We compare the potentially beneficial and harmful roles of BDNF for the mature auditory system with those BDNF functions known in other sensory circuits, such as the vestibular, visual, olfactory, or somatosensory system., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

Conclusion: A man-made bone tunnel of 1.5 turns around the modiolus can be created in cases of total cochlear ossification. Patients with ossified cochlea types I and II achieved satisfactory hearing results after cochlear implantation (CI). Patients with ossified cochlea type III, in which the modiolus is damaged by the ossification, showed poor hearing results after CI., Objectives: To introduce a new CI surgical technique for ossified cochlea and to summarize postoperative hearing results., Methods: A total of 79 patients with ossified cochlea who underwent CI were analyzed. Cases were divided into three types: type I, round window ossification; type II, partial cochlear ossification; and type III, complete cochlear ossification. Four surgical methods were used: method A, applicable to type I; methods B and C, applicable to type II; and method D, applicable to type III. Sound field audiometric and speech tests were performed 6 months postoperatively., Results: All surgeries were successful. The average hearing thresholds for warble tone were 35 dB hearing level (HL) in types I and II and 75 dB HL in type III. The average recognition rates of Mandarin speech were 100% (single finals) and 91% (single initials) in types I and II and 20% (single finals) and 0% (single initials) in type III.

Aminoglycoside antibiotics are highly effective agents against gram-negative bacterial infections, but they cause adverse effects on hearing and balance dysfunction as a result of toxicity to hair cells of the cochlea and vestibular organs. While ototoxicity has been comprehensively studied, the contributions of the immune system, which controls the host response to infection, have not been studied in antibiotic ototoxicity. Recently, it has been shown that an inflammatory response is induced by hair cell injury. In this study, we found that lipopolysaccharide (LPS), an important component of bacterial endotoxin, when given in combination with kanamycin and furosemide, augmented the inflammatory response to hair cell injury and exacerbated hearing loss and hair cell injury. LPS injected into the peritoneum of experimental mice induced a brisk cochlear inflammatory response with recruitment of mononuclear phagocytes into the spiral ligament, even in the absence of ototoxic agents. While LPS alone did not affect hearing, animals that received LPS prior to ototoxic agents had worse hearing loss compared to those that did not receive LPS pretreatment. The poorer hearing outcome in LPS-treated mice did not correlate to changes in endocochlear potential. However, LPS-treated mice demonstrated an increased number of CCR2(+) inflammatory monocytes in the inner ear when compared with mice treated with ototoxic agents alone. We conclude that LPS and its associated inflammatory response are harmful to the inner ear when coupled with ototoxic medications and that the immune system may contribute to the final hearing outcome in subjects treated with ototoxic agents.

Objective: To evaluate the hearing of adolescents with diabetes mellitus type 1(DM1) by otoacoustic emissions (OAEs), and by comparing different tests with pure-tone audiometry to identify potential early cochlear impairments., Design: Pure-tone audiometry, transient evoked otoacoustic emissions (TEOAEs), and distortion product otoacoustic emissions (DPOAEs) were performed in a group of adolescents with and without DM1. Clinical characteristics, disease duration, and glycated haemoglobin levels were studied., Study Sample: Participants were 40 adolescents with DM1 and 40 healthy subjects., Results: Sensorineural hearing loss, affecting frequencies of 6000 and 8000 Hz, was found only in DM1 subjects when compared to the controls (7.7% vs. 0%, p < 0.05). A higher prevalence of cochlear damage was detected by DPOAE responses, 32% belonging from the diabetic group, vs. 3.7% in the control group. Absent TEOAE responses were observed in only three individuals, all from the diabetic group (5.1% of the tests performed in the diabetic group). Additionally, hearing thresholds were better in diabetic subjects with good control when compared to ones with regular or poor control (p = 0.00). Hearing thresholds were higher in poorly controlled diabetics when compared to subjects with good (p = 0.000) or regular control (p = 0.006)., Conclusion: Early evidence of cochlear damage was detected in adolescents with DM1 leading to hearing loss at high frequencies. Abnormal DPOAEs responses were found more frequently than the alterations in TEOAEs and pure-tone audiometry, suggesting that DPOAEs evaluation is the most sensitive and it could be used for monitoring the progression of cochlear damage during the early stages of hearing impairment.

Objective: To demonstrate if cochleopathy in patients with type 2 diabetes with normal audiometric hearing threshold can be detected with otoacoustic emissions or medial olivocochlear (MOC) reflex measurements., Study Design: Cross-sectional study., Setting: Tertiary university teaching hospital., Methods: The study involved 40 type 2 diabetic patients and 24 healthy volunteers. All participants who showed normal otoscopic findings, hearing thresholds, and acoustic admittance were included. Cochlear activity of participants was evaluated by means of distortion product otoacoustic emissions (DPOAEs) and transient otoacoustic emissions (TOAEs). The MOC reflex was evoked with contralateral acoustic stimulation and recorded with DPOAEs and TOAEs., Result: A comparison of DPOAE and TOAE levels with a t test between patient and control groups revealed no significant difference (P > .05). A comparison of the MOC reflex response between the 2 groups also revealed no statistically significant difference (P > .05)., Conclusion: Although decreased OAE amplitude levels were found in diabetic patients, there was no statistically significant difference in OAEs and MOC reflex. Additional studies are needed to evaluate the role of OAEs and MOC reflex in normal-hearing patients with diabetes., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.)

Objectives: To investigate auditory dysfunction in patients with tinnitus and normal hearing thresholds using two sensitive audiological measures., Design: The study was designed to investigate the characteristics of Audioscan and DPOAE tests in tinnitus patients with normal hearing thresholds. Audioscan and DPOAE notches were analysed and compared. All tests were performed in a sound-treated chamber or in a sound-treated room., Study Sample: Forty-five tinnitus patients with normal hearing thresholds were examined following a written clinical protocol., Results: The averaged hearing levels obtained from tinnitus participants were significantly worse at high frequencies than those derived from the normative data. There was a significantly higher prevalence of Audioscan and DPOAE notches, whose central frequencies matched tinnitus frequencies in the mid-frequency regions, but not in the low- and high-frequency regions. A significant correlation was found between the centre frequencies of the Audioscan notches and the DPOAE notches from 500 to 4000 Hz., Conclusion: Tinnitus in different frequency regions may be associated with different underlying mechanisms of tinnitus generation. Some negative results on the Audioscan and DPOAE notches matching tinnitus pitches may be due to a limited set of discrete frequencies used for the tinnitus pitch matching test.

Objectives: The primary aim of this study was to identify the prevalence of dead regions (DRs) in new adult hearing aid referrals and existing adult hearing aid users. Secondary aims included determining the effect of hearing threshold levels and slope, age, and sex on the presence of DRs., Design: Three hundred and seventy-six adults were recruited from a U.K. National Health Service audiology clinic. Three hundred and forty-three participants (674 ears) with a sensorineural hearing impairment were assessed for the presence of a DR at audiometric frequencies from 0.5 to 4 kHz using the Threshold Equalizing Noise test., Results: The overall prevalence of DRs was 36% (95% confidence interval 31-41). The prevalence in new referrals, and in new and existing hearing aid users was 31% (25-37), 33% (26-40), and 43% (35-51), respectively. The overall prevalence of extensive DRs, defined as spanning ≥3 consecutive frequencies, was 3% (1-5)., Conclusions: On the basis of the findings from the Threshold Equalizing Noise test, prevalence of DRs was relatively high in adult hearing aid users with a sensorineural hearing impairment. However, in most cases, the DR was limited to a small frequency region. This suggests that, in most cases, the presence of a DR may not be clinically significant. The difference in DR prevalence between new referrals and existing hearing aid users was not statistically significant. Hearing threshold levels, slope of hearing impairment, age, and sex could not be used to reliably identify DRs.

The inner ear receives two types of efferent feedback from the brainstem: one pathway provides gain control on outer hair cells' contribution to cochlear amplification, and the other modulates the excitability of the cochlear nerve. Although efferent feedback can protect hair cells from acoustic injury and thereby minimize noise-induced permanent threshold shifts, most prior studies focused on high-intensity exposures (>100 dB SPL). Here, we show that efferents are essential for long-term maintenance of cochlear function in mice aged 1 year post-de-efferentation without purposeful acoustic overexposure. Cochlear de-efferentation was achieved by surgical lesion of efferent pathways in the brainstem and was assessed by quantitative analysis of immunostained efferent terminals in outer and inner hair cell areas. The resultant loss of efferent feedback accelerated the age-related amplitude reduction in cochlear neural responses, as seen in auditory brainstem responses, and increased the loss of synapses between hair cells and the terminals of cochlear nerve fibers, as seen in confocal analysis of the organ of Corti immunostained for presynaptic and postsynaptic markers. This type of neuropathy, also seen after moderate noise exposure, has been termed "hidden hearing loss", because it does not affect thresholds, but can be seen in the suprathreshold amplitudes of cochlear neural responses, and likely causes problems with hearing in a noisy environment, a classic symptom of age-related hearing loss in humans. Since efferent reflex strength varies among individuals and can be measured noninvasively, a weak reflex may be an important risk factor, and prognostic indicator, for age-related hearing impairment.

Objective: For diagnostic purposes and a better understanding of the pathophysiology of inner ear hearing disorders it would be of great interest to have parameters available that indicate inner ear hypoxia. In animal studies typical hypoxia-related alterations of the 2f1-f2 distortion product otoacoustic emissions (DPOAE) such as a reversible level decrease and destabilization could be demonstrated. The goal of this study was to investigate whether these hypoxia-associated alterations can also be observed in humans because this might help develop a new diagnostic tool for patients with inner ear disorders., Methods: In 16 volunteers DPOAE levels were continuously measured at first under normal room air conditions, during and after 8.5h of oxygen deprivation (13% O2) and during re-oxygenation. Saturation of oxygen of arterial blood (SaO2) was monitored., Results: The mean SaO2 during the hypoxic interval was 78%. A significant decrease in DPOAE level under hypoxia occurred in five different test persons at one or more frequencies (f2=1, 1.5, 2, 3, and 4kHz). A destabilization of the DPOAE level with considerable fluctuations during hypoxia was observed in nine subjects at one or more frequencies. Furthermore, the so called 'post hypoxia effect' could be observed in five participants., Conclusion: The observations made here have been described similarly in animal studies and seem to be characteristic of metabolic disorders of the cochlea caused by hypoxia. To our knowledge, this is the first study to examine DPOAE level alterations over time in humans under conditions of normobaric hypoxia. If DPOAE destabilization is observed in a clinical setting in patients with certain inner ear hearing disorders hypoxia can be suspected as one underlying pathophysiological cause which might influence treatment decisions., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: The study of tinnitus mechanisms has increased tenfold in the last decade. The common denominator for all of these studies is the goal of elucidating the underlying neural mechanisms of tinnitus with the ultimate purpose of finding a cure. While these basic science findings may not be immediately applicable to the clinician who works directly with patients to assist them in managing their reactions to tinnitus, a clear understanding of these findings is needed to develop the most effective procedures for alleviating tinnitus., Purpose: The goal of this review is to provide audiologists and other health-care professionals with a basic understanding of the neurophysiological changes in the auditory system likely to be responsible for tinnitus., Results: It is increasingly clear that tinnitus is a pathology involving neuroplastic changes in central auditory structures that take place when the brain is deprived of its normal input by pathology in the cochlea. Cochlear pathology is not always expressed in the audiogram but may be detected by more sensitive measures. Neural changes can occur at the level of synapses between inner hair cells and the auditory nerve and within multiple levels of the central auditory pathway. Long-term maintenance of tinnitus is likely a function of a complex network of structures involving central auditory and nonauditory systems., Conclusions: Patients often have expectations that a treatment exists to cure their tinnitus. They should be made aware that research is increasing to discover such a cure and that their reactions to tinnitus can be mitigated through the use of evidence-based behavioral interventions., (American Academy of Audiology.)

Aging listeners experience greater difficulty understanding speech in adverse listening conditions and exhibit degraded temporal resolution, even when audiometric thresholds are normal. When threshold evidence for peripheral involvement is lacking, central and cognitive factors are often cited as underlying performance declines. However, previous work has uncovered widespread loss of cochlear afferent synapses and progressive cochlear nerve degeneration in noise-exposed ears with recovered thresholds and no hair cell loss (Kujawa and Liberman 2009). Here, we characterize age-related cochlear synaptic and neural degeneration in CBA/CaJ mice never exposed to high-level noise. Cochlear hair cell and neuronal function was assessed via distortion product otoacoustic emissions and auditory brainstem responses, respectively. Immunostained cochlear whole mounts and plastic-embedded sections were studied by confocal and conventional light microscopy to quantify hair cells, cochlear neurons, and synaptic structures, i.e., presynaptic ribbons and postsynaptic glutamate receptors. Cochlear synaptic loss progresses from youth (4 weeks) to old age (144 weeks) and is seen throughout the cochlea long before age-related changes in thresholds or hair cell counts. Cochlear nerve loss parallels the synaptic loss, after a delay of several months. Key functional clues to the synaptopathy are available in the neural response; these can be accessed noninvasively, enhancing the possibilities for translation to human clinical characterization.

One of the hypotheses on the etiology of non-pulsatile tinnitus in normal or hearing impaired patients is the existence of sharp edged cochlear dead regions (DR) flanking normal functioning hair cells. The lack of inhibition of DR on the neighboring neurons may lead to hyperactivity. Currently the Threshold Equalizing Noise test (TEN test) is the reference test to clinically assess cochlear DR. To identify cochlear DR in patients with non-pulsatile tinnitus with and without hearing loss using the TEN (sound pressure level)-test. Data were obtained from adult patients with non-pulsatile tinnitus visiting the Tinnitus Clinic of the University Hospital Antwerp. The TEN (SPL)-test was performed to assess the presence of cochlear DR for test frequencies ranging from 0.5 to 8 kHz. A total of 55 ears of 33 subjects (15 male; 18 female) with non-pulsatile tinnitus were included in the study. Subjects were divided into subgroups based on the audiometric configuration of hearing loss: Flat configuration (N = 23), high-frequency gently sloping (N = 10) and high-frequency steeply sloping (N = 22). In forty-eight ears there was no evidence of cochlear DR. In seven ears the results were inconclusive. This occurred in patients with high-frequency steeply sloping audiogram configurations. The present study does not support the TEN (SPL) test as a reliable tool for the detection of cochlear DR in a tinnitus population.

3-Nitropropionic acid (3-NP), a mitochondrial toxin, has been reported to induce an acute cochlear damage. Korean red ginseng (KRG) is known to have protective effects from some types of hearing loss. This study aimed to observe the protective effect of KRG in an ototoxic animal model using 3-NP intratympanic injection. BALB/c mice were classified into 5 groups (n=15) and dose-dependent toxic effects after intratympanic injection with 3-NP (300-5000 mM) on the left ear were investigated to determine the appropriate toxicity level of 3-NP. For observation of the protective effects of KRG, 23 mice were grouped into 3-NP (500 mM, n=12) and KRG+3-NP groups (300 mg/kg KRG for 7 days before 500 mM 3-NP administration, n=11). Auditory brain response (ABR) and cochlear morphological evaluations were performed before and after drug administration. The ABR thresholds in the 800-5000 mM groups exceeded the maximum recording limit at 16 and 32 kHz 1 day after 3-NP administration. The ABR threshold in the 500 mM 3-NP+KRG group was significantly lower than that in the 500 mM 3-NP group from post 1 week to 1 month. The mean type II fibrocyte counts significantly differed between the control and 3-NP groups and between the 3-NP and 3-NP+KRG groups. Spiral ganglion cell degeneration in the 3-NP group was more severe than that in the 3-NP+KRG group. This animal model exhibited a dose-dependent hearing loss with histological changes. KRG administration ameliorated the deterioration of hearing by 3-NP., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: According to current diagnostic criteria, patients exhibiting only cochlear symptoms without vertigo cannot be diagnosed with Ménière's disease (MD). The recently reported Ménière's Disease Index (MDI) combines audiometric and electrocochleographic parameters in a multidimensional measure correlating with the clinical degrees of MD., Materials and Methods: Twenty-one patients with hearing loss, tinnitus and aural fullness, but without vertigo, underwent transtympanic electrocochleography. Based on the previously reported formula, the MDI value for every patient was calculated., Results: Mean MDI value was 5.7 on a scale from 0 (mean value of non-MD patients) to 10 (mean value of definite MD patients)., Conclusions: We can thus hypothesize that, based on audiometry and electrocochleography, 'cochlear MD' patients may represent a separate clinical entity with Ménière-like pathophysiology or underlying endolymphatic hydrops., (Copyright © 2012 S. Karger AG, Basel.)

The ability of eight normal-hearing listeners and fourteen listeners with sensorineural hearing loss to detect and identify pitch contours was measured for binaural-pitch stimuli and salience-matched monaurally detectable pitches. In an effort to determine whether impaired binaural pitch perception was linked to a specific deficit, the auditory profiles of the individual listeners were characterized using measures of loudness perception, cognitive ability, binaural processing, temporal fine structure processing, and frequency selectivity, in addition to common audiometric measures. Two of the listeners were found not to perceive binaural pitch at all, despite a clear detection of monaural pitch. While both binaural and monaural pitches were detectable by all other listeners, identification scores were significantly lower for binaural than for monaural pitch. A total absence of binaural pitch sensation coexisted with a loss of a binaural signal-detection advantage in noise, without implying reduced cognitive function. Auditory filter bandwidths did not correlate with the difference in pitch identification scores between binaural and monaural pitches. However, subjects with impaired binaural pitch perception showed deficits in temporal fine structure processing. Whether the observed deficits stemmed from peripheral or central mechanisms could not be resolved here, but the present findings may be useful for hearing loss characterization.