Human Temporal Bone Study Research Articles

Assessing the manufacturable 32-channel cochlear electrode array: evaluation results for clinical trials.

Reliability evaluation results of a manufacturable 32-channel cochlear electrode array are reported in this paper. Applying automated laser micro-machining process and a layer-by-layer silicone deposition scheme, authors developed the manufacturing methods of the electrode array for fine patterning and mass production. The developed electrode array has been verified through the requirements specified by the ISO Standard 14708-7. And the insertion trauma of the electrode array has been evaluated based on human temporal bone studies. According to the specified requirements, the electrode array was assessed through elongation & insulation, flexural, and fatigue tests. In addition, Temporal bone study was performed using eight fresh-frozen cadaver temporal bones with the electrode arrays inserted via the round window. Following soaking in saline condition, the impedances between conducting wires of the electrode array were measured over 100 kΩ (the pass/fail criterion). After each required test, it was shown that the electrode array maintained the electrical continuity and insulation condition. The average insertion angle of the electrode array inside the scala tympani was 399.7°. The human temporal bone studies exhibited atraumatic insertion rate of 60.3% (grade 0 or 1). The reliability of the manufacturable electrode array is successfully verified in mechanical, electrical, and histological aspects. Following the completion of a 32-channel cochlear implant system, the performance and stability of the 32-channel electrode array will be evaluated in clinical trials.

Archival Human Temporal Bone: Anatomical and Histopathological Studies of Cochlear Implantation.

Since being FDA approved in 1984, cochlear implantation has been used successfully to restore hearing in those with severe to profound hearing loss with broader applications including single-sided deafness, the use of hybrid electroacoustic stimulation, and implantation at all extremes of age. Cochlear implants have undergone multiple changes in the design aimed at improving the processing technology, while simultaneously minimizing the surgical trauma and foreign body reaction. The following review examines the human temporal bone studies regarding the anatomy of the human cochlea and how the anatomy relates to cochlear implant design, the factors related to complications after implantation, and the predictors of new tissue formation and osteoneogenesis. Histopathological studies are reviewed which aim to understand the potential implications of the effects of new tissue formation and inflammation following implantation.

Mechanisms Underlying the Formation of Endolymphatic Hydrops and the Inner Ear Disorder

Yamakawa first reported endolymphatic hydrops (EH) in a patient with Meniere’s disease (MD) in 1938. In the same year, Hallpike and Cairns also reported the association between MD and EH and established the modern diagnosis of MD. This association is now widely accepted; however, doubts have recently been raised. A recent human temporal bone study review failed to conclude if the association is an epiphenomenon or whether EH causes MD.

Pathological significance and classification of endolymphatic hydrops in otological disorders.

ABSTRACTWe summarize the presence of endolymphatic hydrops (EH) in otological disorders evaluated with magnetic resonance imaging (MRI) of temporal bones, and propose a classification of EH based on its pathological significance. A search of the literature published in English-language journals was performed using electronic databases, especially focusing on EH-related otological disorders. Clinical articles that contained the terms EH and contrast-MRI published from 2007 to the present, with relevant human temporal bone studies, were included. The following three main points are discussed based on the results in the relevant articles: i) otological disorders that present EH, ii) current grading for evaluation of EH on MRI, and iii) a proposed classification of EH based on its pathological significance. MRI evaluation revealed that EH exists extensively not only in ears with typical Meniere’s disease (MD), but also in those with various other otological disorders. The etiological classification of EH helps to summarize ideas for determining the pathophysiology of otological disorders, while a therapeutic classification provides clues to their management. MRI evaluations of EH have led to breakthroughs in investigations of EH in otological disorders. Precise grading for evaluation and clarification of EH on MRI based on its pathological significance could provide keys to elucidating the pathophysiology of EH-related otological disorders.

CT imaging-based approaches to cochlear duct length estimation\u2014a human temporal bone study

ObjectivesKnowledge about cochlear duct length (CDL) may assist electrode choice in cochlear implantation (CI). However, no gold standard for clinical applicable estimation of CDL exists. The aim of this study is (1) to determine the most reliable radiological imaging method and imaging processing software for measuring CDL from clinical routine imaging and (2) to accurately predict the insertion depth of the CI electrode.MethodsTwenty human temporal bones were examined using different sectional imaging techniques (high-resolution computed tomography [HRCT] and cone beam computed tomography [CBCT]). CDL was measured using three methods: length estimation using (1) a dedicated preclinical 3D reconstruction software, (2) the established A-value method, and (3) a clinically approved otosurgical planning software. Temporal bones were implanted with a 31.5-mm CI electrode and measurements were compared to a reference based on the CI electrode insertion angle measured by radiographs in Stenvers projection (CDLreference).ResultsA mean cochlear coverage of 74% (SD 7.4%) was found. The CDLreference showed significant differences to each other method (p < 0.001). The strongest correlation to the CDLreference was found for the otosurgical planning software-based method obtained from HRCT (CDLSW-HRCT; r = 0.87, p < 0.001) and from CBCT (CDLSW-CBCT; r = 0.76, p < 0.001). Overall, CDL was underestimated by each applied method. The inter-rater reliability was fair for the CDL estimation based on 3D reconstruction from CBCT (CDL3D-CBCT; intra-class correlation coefficient [ICC] = 0.43), good for CDL estimation based on 3D reconstruction from HRCT (CDL3D-HRCT; ICC = 0.71), poor for CDL estimation based on the A-value method from HRCT (CDLA-HRCT; ICC = 0.29), and excellent for CDL estimation based on the A-value method from CBCT (CDLA-CBCT; ICC = 0.87) as well as for the CDLSW-HRCT (ICC = 0.94), CDLSW-CBCT (ICC = 0.94) and CDLreference (ICC = 0.87).ConclusionsAll approaches would have led to an electrode choice of rather too short electrodes. Concerning treatment decisions based on CDL measurements, the otosurgical planning software-based method has to be recommended. The best inter-rater reliability was found for CDLA-CBCT, for CDLSW-HRCT, for CDLSW-CBCT, and for CDLreference.Key Points• Clinically applicable calculations using high-resolution CT and cone beam CT underestimate the cochlear size.• Ten percent of cochlear duct length need to be added to current calculations in order to predict the postoperative CI electrode position.• The clinically approved otosurgical planning software-based method software is the most suitable to estimate the cochlear duct length and shows an excellent inter-rater reliability.

Temporal Bone Pathology Secondary to Head Trauma-A Human Temporal Bone Study.

We hypothesize that following head trauma there is a difference in temporal bone (TB) pathology in cases with and without skull fracture. Although conductive, sensorineural, mixed hearing loss, and TB pathology following head trauma have been reported, to our knowledge, there are no studies that have compared the pathology of the TB in cases with and without skull fracture. We analyzed 34 TBs from donors who had a history of head trauma (20 with skull fracture and 14 without fracture), and 25 age-matched controls without clinical or histological evidence of otologic disorders. We documented the presence and location of TB fracture, ossicular injury, and cochlear hemorrhage and evaluated the loss of spiral ganglion cells and sensory hair cells, damage to the stria vascularis, and the presence of endolymphatic hydrops. We found a significant loss of outer hair cells in the upper basal, lower, and upper middle turns of the cochlea (p = 0.009, =0.019, =0.040, respectively), a significant loss of spiral ganglion cells (p = 0.023), and cochlear hemorrhage predominantly in the basal turns secondary to head trauma. Interestingly, these findings were significantly observed in TBs from donors with a history of head trauma without skull fracture. The greatest damage was to the cochlear basal turn. Our findings suggest that head trauma may result in tonotopic high frequency sensorineural hearing loss. TBs from donors with skull fracture have less pathologic changes than those without.

Comparison of Age-Related Pigmentary Changes in the Auditory and Vestibular Systems Within Mouse and Human Temporal Bones.

BackgroundMelanin pigmentation is present within the auditory and vestibular systems of the mammalian inner ear and may play a role in maintaining auditory and vestibular function. Melanocytes within the stria vascularis (SV) are necessary for the generation of the endocochlear potential (EP) and decreased EP has been linked to age-related hearing loss. Melanocytes and pigment-containing “dark cells” are present within the vestibular system, but have a less well-defined role. African–American individuals have increased pigmentation within the SV and vestibular system, which is hypothesized to be related to lower rates of age-related hearing loss and vestibular dysfunction. It remains unclear if increased pigmentation confers lifelong protection against hearing loss and vestibular dysfunction.MethodsMouse temporal bones were collected from juvenile (3–4 week) and aged (20–32 months) CBA/CaJ mice. Pediatric and adult human temporal bones from Caucasian or African–American individuals were examined from the Johns Hopkins Temporal Bone Collection. Information regarding Fitzpatrick skin type were unavailable, and self-identified race/ethnicity was used as a proxy. Images were taken using light microscopy at 20× magnification. ImageJ software (v1.53) was used to measure pigment within the SV and vestibular system.ResultsIn mouse temporal bones pigmentation within the SV increased with age, but pigmentation within the vestibular system did not increase with age. In human temporal bones pigmentation within the SV increased with age and pigmentation within the vestibular system increased within the wall of the utricle, but not other regions of the vestibular system. African–American individuals had higher amounts of pigment within the SV and vestibular system, among both pediatric and adult populations.ConclusionStria vascularis pigmentation increases with age in mouse and human temporal bones. Pigmentation within the vestibular system did not increase with age in mouse specimens and only increased within the utricular wall with age in human specimens. Individuals who identified as African–American had higher pigment content within the SV and vestibular system, both as children and as adults. These results highlight how similar age-related pigmentary changes occur in the auditory and vestibular systems across species and underscore the importance of racial/ethnic diversity in human temporal bone studies.

Evaluating Neurotrophin Signaling Using MicroRNA Perilymph Profiling in Cochlear Implant Patients With and Without Residual Hearing.

MicroRNAs predicted to regulate neurotrophin signaling can be found in human perilymph. Animal and human temporal bone studies suggest that spiral ganglion health can affect cochlear implant (CI) outcomes. Neurotrophins have been identified as a key factor in the maintenance of spiral ganglion health. Changes in miRNAs may regulate neurotrophin signaling and may reflect neurotrophin expression levels. Perilymph sampling was carried out in 18 patients undergoing cochlear implantation or stapedotomy. Expression of miRNAs in perilymph was evaluated using an Agilent miRNA gene chip. Using ingenuity pathway analysis (IPA) software, miRNAs targeting neurotrophin signaling pathway genes present in a cochlear cDNA library were annotated. Expression levels of miRNAs in perilymph were correlated to the patients' preoperative pure-tone average. Expression of mRNAs coding for neurotrophins and their receptors were identified in tissue obtained from normal human cochlea during skull base surgery. We identified miRNAs predicted to regulate these signaling cascades, including miR-1207-5p, miR-4651, miR-103-3p, miR-100-5p, miR-221-3p, miR-200-3p. There was a correlation between poor preoperative hearing and lower expression of miR-1207 (predicted to regulate NTR3) and miR-4651 (predicted to regulate NTR2). Additionally, miR-3960, miR-4481, and miR-675 showed significant differences in expression level when comparing mild and profound hearing loss patients. Expression of some miRNAs that are predicted to regulate neurotrophin signaling in the perilymph of cochlear implant patients vary with the patient's level of residual hearing. These miRNAs may serve as biomarkers for changes in neurotrophin signaling.

Histology and neuroanatomy suggest a unified mechanism to explain the distribution of lesion patterns in acute vestibular neuropathy.

Human temporal bone studies have described the distribution of afferent fibers from each of the five organelles in the labyrinth. Data from vestibular tests in patients with vestibular neuritis can be abnormal in almost any pattern. We propose a unified explanation for these patterns, based on histological and neuroanatomical factors.

The Use of Clinically Measurable Cochlear Parameters in Cochlear Implant Surgery as Indicators for Size, Shape, and Orientation of the Scala Tympani.

(1) To assess variations of the human intracochlear anatomy and quantify factors which might be relevant for cochlear implantation (CI) regarding surgical technique and electrode design. (2) Search for correlations of these factors with clinically assessable measurements. Human temporal bone study with micro computed tomography (μCT) data and analysis of intracochlear geometrical variations: μCT data of 15 fresh human temporal bones was generated, and the intracochlear lumina scala tympani (ST) and scala vestibuli were manually segmented using custom software specifically designed for accurate cochlear segmentation. The corresponding datasets were processed yielding 15 detailed, three-dimensional cochlear models which were investigated in terms of the scalae height, cross-sectional size, and rotation as well as the interrelation of these factors and correlations to others. The greatest anatomical variability was observed within the round window region of the cochlea (basal 45°), especially regarding the cross-sectional size of the ST and its orientation relative to the scala vestibuli, which were found to be correlated (p < 0.001). The cross-sectional height of the ST changes substantially for both increasing cochlear angles and lateral wall distances. Even small cochleae were found to contain enough space for all commercially available CI arrays. Significant correlations of individual intracochlear parameters to clinically assessable ones were found despite the small sample size. While there is generally enough space within the ST for CI, strong intracochlear anatomical variations could be observed highlighting the relevance of both soft surgical technique as well as a highly flexible and self-adapting cochlear implant electrode array design. Cochlear dimensions (especially at the round window) could potentially be used to indicate surgically challenging anatomies.

Characterization of the Sheep Round Window Membrane.

Intratympanic injection is a clinically used approach to locally deliver therapeutic molecules to the inner ear. Drug diffusion, at least in part, is presumed to occur through the round window membrane (RWM), one of the two openings to the inner ear. Previous studies in human temporal bones have identified a three-layered structure of the RWM with a thickness of 70-100μm. This is considerably thicker than the RWM in rodents, which are mostly used to model RWM permeability and assess drug uptake. The sheep has been suggested as a large animal model for inner ear research given the similarities in structure and frequency range for hearing. Here, we report the structure of the sheep RWM. The RWM is anchored within the round window niche (average vertical diameter of 2.1 ± 0.3mm and horizontal diameter of 2.3 ± 0.4mm) and has a curvature that leans towards the scala tympani. The centre of the RWM is the thinnest (55-71μm), with increasing thickness towards the edges (< 171μm), where the RWM forms tight attachments to the surrounding bony niche. The layered RWM structure, including an outer epithelial layer, middle connective tissue and inner epithelial layer, was identified with cellular features such as wavy fibre bundles, melanocytes and blood vessels. An attached "meshwork structure" which extends over the cochlear aqueduct was seen, as in humans. The striking anatomical similarities between sheep and human RWM suggest that sheep may be evaluated as a more appropriate system to predict RWM permeability and drug delivery in humans than rodent models.

Absence of Endolymphatic Sac Ion Transport Proteins in Large Vestibular Aqueduct Syndrome—A Human Temporal Bone Study

Epithelial ion transport pathologies of the endolymphatic sac (ES) are associated with large vestibular aqueduct syndrome (LVAS). LVAS is defined by the pathognomonic features of a widened bony vestibular aqueduct (VA) and an enlarged ES. The underlying cause of its associated cochleovestibular symptoms remains elusive. Disturbances in epithelial ion transport in the enlarged ES, affecting inner ear fluid regulation, were proposed as a possible pathophysiology. However, although respective epithelial ion transport pathologies have been demonstrated in the enlarged ES from transgenic LVAS mouse models, these pathologies have not been investigated in human LVAS cases. Histological and immunohistochemical analysis of the enlarged ES epithelium in postmortem temporal bones from two individuals with a clinical diagnosis of LVAS. The enlarged ES epithelium demonstrated an overall atypical epithelial differentiation and a lack of the immunolocalization of signature ion transport proteins. Notably, in both cases, a rudimentary branch of the ES with a typically differentiated ES epithelium was present. The described cellular and molecular pathologies of the enlarged ES in humans provide evidence of epithelial transport pathology as one potential cause of cochleovestibular symptoms in LVAS. The present findings also emphasize the clinical relevance of already established LVAS mouse models.

Electrophysiological Estimates of the Electrode-Neuron Interface Differ Between Younger and Older Listeners With Cochlear Implants.

The primary objective of this study was to quantify differences in evoked potential correlates of spiral ganglion neuron (SGN) density between younger and older individuals with cochlear implants (CIs) using the electrically evoked compound action potential (ECAP). In human temporal bone studies and in animal models, SGN density is the lowest in older subjects and in those who experienced long durations of deafness during life. SGN density also varies as a function of age at implantation and hearing loss etiology. Taken together, it is likely that younger listeners who were deafened and implanted during childhood have denser populations of SGNs than older individuals who were deafened and implanted later in life. In animals, ECAP amplitudes, amplitude growth function (AGF) slopes, and their sensitivity to stimulus interphase gap (IPG) are predictive of SGN density. The authors hypothesized that younger listeners who were deafened and implanted as children would demonstrate larger ECAP amplitudes, steeper AGF slopes, and greater IPG sensitivity than older, adult-deafened and implanted listeners. Data were obtained from 22 implanted ears (18 individuals). Thirteen ears (9 individuals) were deafened and implanted as children (child-implanted group), and nine ears (9 individuals) were deafened and implanted as adults (adult-implanted group). The groups differed significantly on a number of demographic variables that are implicitly related to SGN density: (1) chronological age; (2) age at implantation; and (3) duration of preimplantation hearing loss. ECAP amplitudes, AGF linear slopes, and thresholds were assessed on a subset of electrodes in each ear in response to two IPGs (7 and 30 µsec). Speech recognition was assessed using a medial vowel identification task. Compared with the adult-implanted listeners, individuals in the child-implanted group demonstrated larger changes in ECAP amplitude when the IPG of the stimulus was increased from 7 to 30 µsec (i.e., greater IPG sensitivity). On average, child-implanted participants also had larger ECAP amplitudes and steeper AGF linear slopes than the adult-implanted participants, irrespective of IPG. IPG sensitivity for AGF linear slope and ECAP threshold did not differ between age groups. Vowel recognition performance was not correlated with any of the ECAP measures assessed in this study. The results of this study support the theory that young CI listeners who were deafened and implanted during childhood may have denser neural populations than older listeners who were deafened and implanted as adults. Potential between-group differences in SGN integrity emphasize a need to investigate optimized CI programming parameters for younger and older listeners.

Otopathologic Analysis of Patterns of Postmeningitis Labyrinthitis Ossificans.

Labyrinthitis ossificans (LO) may occur following meningitis and, in cases where cochlear implantation is indicated, complicate electrode insertion. LO is critical to identify for successful cochlear implantation, and histopathology is more sensitive than imaging for identification of LO. Herein we utilize otopathologic techniques to study the timing and location of intracochlear tissue formation following meningitic labyrinthitis (ML). Retrospective review. Academic institution. Temporal bone specimens with a history of bacterial ML were histologically evaluated. The location and extent of intracochlear tissue formation within the scala tympani (ST) and scala vestibuli (SV) were graded, and spiral ganglion neurons were counted. Fifty-one temporal bones were identified: 32 with no intracochlear tissue formation, 9 with fibrosis alone, and 10 with LO. Fibrosis was identified as early as 1.5 weeks after ML, while ossification was found only in specimens that survived multiple years after ML. All LO cases showed ossification of the ST at the round window membrane (RWM) with continuous extension throughout the basal turn. Extent of SV ossification correlated with that in the ST but showed frequent isolated distal involvement of the cochlea. Spiral ganglion neuron counts were lower than those in age-matched controls. In this human temporal bone study, we found that postmeningitic LO results in ossification at the RWM with continuous extension into the ST of the basal turn and variable involvement of the SV. Identification of a patent basal turn beyond RWM ossification of the ST should permit full electrode insertion. Retrospective review.

Effect of age on envelope regularity discrimination.

The ability to discriminate irregular from regular amplitude modulation was compared for young and older adults with audiometric thresholds within the normal range for frequencies from 250 to 8000 Hz, using the "envelope regularity discrimination" (ERD) test. The amount of irregularity was parametrically varied and quantified by an "irregularity index." The carrier frequency was 2000 Hz, the modulation rate was 8 Hz, and the baseline modulation index was 0.3. Stimuli were presented both at 80 dB sound pressure level (SPL) and at 20 dB sensation level (SL) in the presence of a threshold-equalizing noise. There was a significant effect of level, performance being better at 80 dB SPL than at 20 dB SL. There was also a significant effect of age, performance being worse for the older subjects. There was no significant interaction of level and age. The thresholds for the ERD test were not significantly correlated with absolute thresholds at the test carrier frequency of 2000 Hz, for either group, or for the two groups combined. The worse envelope regularity discrimination for the older group may be related to the age-related synaptopathy that has been established from recent studies of human temporal bones.

Abnormal Tectorial Membranes in Sensorineural Hearing Loss: A Human Temporal Bone Study.

This study evaluates the morphological changes of the tectorial membrane (TM) in conjunction with degeneration of hair cells, interdental cells, and presence of endolymphatic hydrops (EH) in sensorineural hearing loss (HL) in the human using histopathology techniques. The TM plays an important role in mechanical transduction of acoustic energy, and pathology of the TM may result in HL. All temporal bone (TB) specimens from the Massachusetts Eye and Ear Otopathology Laboratory from patients with various causes of sensorineural HL and morphological abnormalities of the TM were evaluated. Cases with a history of cochlear trauma (other than acoustic trauma) and/or severe postmortem artifacts were excluded. The TBs were processed histologically, and the status of hair cells, supporting cells, interdental cells, presence of EH, and postmortem time were tabulated. Two thousand two hundred ninety TBs from 1340 individuals were evaluated, and 164 of 748 TBs from the otological disorders in which the TM were abnormal, met the inclusion criteria. The most common disorders were idiopathic sudden deafness (57.1%), genetic etiology (53.7%), and ototoxicity (40.0%), as compared with cases with presbycusis (2.9%). EH was found in 33.3% of all cases with an identified abnormality of the TM.Abnormalities of the TM were 1) deformed, 2) shrunken, 3) detached from the limbus, 4) encapsulated, or 5) missing. Encapsulated, shrunken and missing patterns (36, 35, 31%, respectively) were the most common. A relative high prevalence of EH among disorders with TM abnormalities suggests a possible common pathophysiology in both. In addition, anatomic abnormalities of the TM may play a role in the pathophysiology of HL in these disorders.

Otopathology in the United States: History, Current Situation, and Future Perspectives.

: Human temporal bone studies have documented the pathophysiologic basis of many pathologic conditions and diseases affecting the ear, contributing to the development of specific clinical knowledge and pathology-oriented treatments. Researchers dedicated to the study of anatomy and histology of the temporal bone emanated from Europe to the United States during the first part of the 20th Century. The first otopathology laboratory was founded in the United States in 1924, at Johns Hopkins University; over time, the otopathology laboratories-considered by some authors as "gold mines" for studying ear diseases-became numerous and very prolific. However, today, only three of the temporal bone laboratories are still running and producing scientific knowledge to the Otology/Neurotology field: the ones at Harvard Medical School, University of Minnesota, and University of California. Molecular biologic assay techniques and new microscopy and computer equipment broadened the possibilities for temporal bone studies; however, the current funding for those laboratories are insufficient to cover the costs for processing and studying human temporal bones. The main objective of this study is to briefly describe the history, current situation, and future perspectives of the otopathology laboratories in the United States.

Impact of anatomical variations on insertion forces

Abstract The choice of a cochlear implant electrode carrier for the individual patient is influenced by cochlear size, as this parameter has an impact on the risk of scala dislocations. Therefore, size and morphology should be represented in artificial cochlear models too, since these are generally used for insertion studies evaluating newly developed cochlear implant electrode carriers and insertion techniques, before human temporal bone studies are applied for. Within this study custom-made electrode carrier test samples were inserted into nine artificial cochlear models of different shape. To fabricate them, four human temporal bone samples have been processed by a serial cross-sectioning technique; the other four samples have been scanned with micro computed tomography. The cochlea was segmented on this data using rotating, midmodiolar slice planes, followed by the generation of a three-dimensional digital model, which finally was projected on a plane and 2D models were milled out of PTFE. The ratios of length to width of the cochlear basal turn of our samples were found to be within previously reported range. For comparative reasons a model used in previous studies was included in this study too. The maximal insertion forces per cochlear model followed a normal distribution. The insertion depth at initial insertion force increase is correlated to the length of cochlear basal turn. Using the here presented cochlear models with varying anatomical measures may help to increase the clinical relevance of insertion studies in artificial cochlear models.

Connexin 26 Immunohistochemistry in Temporal Bones With Cochlear Otosclerosis.

Connexin-26 (Cx26) expression is diminished in the spiral ligament of subjects with hearing loss and cochlear otosclerosis (CO). Human temporal bone (HTB) studies have demonstrated that CO is associated with hyalinization of the spiral ligament. We hypothesize that hyalinization is associated with a loss of fibrocytes with a consequent decline in Cx26 expression. Cx26 and Connexin-30 (Cx30) encode gap junction proteins expressed in supporting cells of the organ of Corti, the spiral limbus, stria vascularis, and in fibrocytes of the spiral ligament. These gap junctions are critical for potassium recycling and maintenance of the endocochlear potential. Diminished expression of these proteins would likely be associated with hearing dysfunction. Histopathology and clinical characteristics of 45 HTB specimens with CO and spiral ligament hyalinization were reviewed. Those with sensorineural or mixed hearing loss but normal or near-normal hair cell counts were analyzed with light microscopy, and Cx26-immunoreactive (IR) signal was qualitatively assessed. H&E staining demonstrated hyalinization in the spiral ligament and loss of type II and type III fibrocytes. Cx26-IR was diminished throughout the cochlea affected with CO compared with normal controls. Cx26-IR reduction in the spiral ligament of subjects with CO likely plays a role in hearing loss.

Perceptual consequences of cochlear synaptopathy in middle age

It is known that as the body ages, listening in noisy situations becomes increasingly more difficult. Middle-aged people have more difficulty than younger people in complex listening environments, even with similar audiometric thresholds. One hypothesis for why this might be is age-related cochlear synaptopathy. Cochlear synaptopathy has been robustly observed to occur with normal aging in animals, and in post-mortem studies of human temporal bones harvested at different ages. However, there are currently no clinical assessments to measure cochlear synaptopathy or the perceptual consequences of this phenomenon. Currently, we are evaluating a battery of clinical and laboratory measures by comparing young and middle-aged listeners with matched audiometric thresholds within the normal range. The battery includes both objective physiological measures that correlate with synaptopathy in animal models, and perceptual measures that hypothetically may be sensitive to synaptopathy-mediated loss of redundancy in afferent coding. Here, we discuss our initial findings within these parameters.It is known that as the body ages, listening in noisy situations becomes increasingly more difficult. Middle-aged people have more difficulty than younger people in complex listening environments, even with similar audiometric thresholds. One hypothesis for why this might be is age-related cochlear synaptopathy. Cochlear synaptopathy has been robustly observed to occur with normal aging in animals, and in post-mortem studies of human temporal bones harvested at different ages. However, there are currently no clinical assessments to measure cochlear synaptopathy or the perceptual consequences of this phenomenon. Currently, we are evaluating a battery of clinical and laboratory measures by comparing young and middle-aged listeners with matched audiometric thresholds within the normal range. The battery includes both objective physiological measures that correlate with synaptopathy in animal models, and perceptual measures that hypothetically may be sensitive to synaptopathy-mediated loss of redundancy in af...