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Jian Wang - One of the best experts on this subject based on the ideXlab platform.
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noise induced cochlear Synaptopathy and signal processing disorders
Neuroscience, 2019Co-Authors: Hengchao Chen, Shankai Yin, Jian Wang, Lijuan Shi, Lijie Liu, Steven J AikenAbstract:Noise-induced hidden hearing loss (NIHHL) has attracted great attention in hearing research and clinical audiology since the discovery of significant noise-induced synaptic damage in the absence of permanent threshold shifts (PTS) in animal models. Although the extant evidence for this damage is based on animal models, NIHHL likely occurs in humans as well. This review focuses on three issues concerning NIHHL that are somewhat controversial: (1) whether disrupted synapses can be re-established; (2) whether synaptic damage and repair are responsible for the initial temporal threshold shifts (TTS) and subsequent recovery; and (3) the relationship between the synaptic damage and repair processes and neural coding deficits. We conclude that, after a single, brief noise exposure, (1) the damaged and the totally destroyed synapses can be partially repaired, but the repaired synapses are functionally abnormal; (2) While deficits are observed in some aspects of neural responses related to temporal and intensity coding in the auditory nerve, we did not find strong evidence for hypothesized coding-in-noise deficits; (3) the sensitivity and the usefulness of the envelope following responses to amplitude modulation signals in detecting cochlear Synaptopathy is questionable.
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coding in noise deficits are not seen in responses to amplitude modulation in subjects with cochlear Synaptopathy induced by a single noise exposure
Neuroscience, 2019Co-Authors: Hengchao Chen, Yazhi Xing, Zhen Zhang, Shan Tao, Hui Wang, Steve Aiken, Shankai Yin, Jian WangAbstract:Since the first report of noise-induced synaptic damage in animals without permanent threshold shifts (PTSs), the concept of noise-induced hidden hearing loss (NIHHL) has been proposed to cover the functional deficits in hearing associated with noise-induced Synaptopathy. Moreover, the potential functional deficit associated with the noise-induced Synaptopathy has been largely attributed to the loss of auditory nerve fibers (ANFs) with a low spontaneous spike rate (SSR). As this group of ANFs is critical for coding at suprathreshold levels and in noisy background, coding-in-noise deficit (CIND) has been considered to be main consequence of the Synaptopathy. However, such deficits have not been verified after a single, brief exposure to noise without PTS. In the present study, Synaptopathy was generated by such noise exposure in both mice and guinea pigs. Responses to amplitude modulation (AM) were recorded at a high sound level in combination with masking to evaluate the existence of CINDs that might be associated with loss of low-SSR ANFs. An overall reduction in response amplitude was seen in AM-evoked compound action potential (CAP). However, no such reduction was seen in the scalp-recorded envelope following response (EFR), suggesting a compensation due to increased central gain. Moreover, there was no significant difference in masking effect between the control and noise groups. The results suggest that either there is no significant CIND after the Synaptopathy we created, or the AM response tested with our protocol was not sufficiently sensitive to detect such a deficit; far-field EFR is not sensitive to cochlear pathology.
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cochlear Synaptopathy and noise induced hidden hearing loss
Neural Plasticity, 2016Co-Authors: Lijuan Shi, Steve Aiken, Ying Chang, Lijie Liu, Jian WangAbstract:Recent studies on animal models have shown that noise exposure that does not lead to permanent threshold shift (PTS) can cause considerable damage around the synapses between inner hair cells (IHCs) and type-I afferent auditory nerve fibers (ANFs). Disruption of these synapses not only disables the innervated ANFs but also results in the slow degeneration of spiral ganglion neurons if the synapses are not reestablished. Such a loss of ANFs should result in signal coding deficits, which are exacerbated by the bias of the damage toward synapses connecting low-spontaneous-rate (SR) ANFs, which are known to be vital for signal coding in noisy background. As there is no PTS, these functional deficits cannot be detected using routine audiological evaluations and may be unknown to subjects who have them. Such functional deficits in hearing without changes in sensitivity are generally called “noise-induced hidden hearing loss (NIHHL).” Here, we provide a brief review to address several critical issues related to NIHHL: (1) the mechanism of noise induced synaptic damage, (2) reversibility of the synaptic damage, (3) the functional deficits as the nature of NIHHL in animal studies, (4) evidence of NIHHL in human subjects, and (5) peripheral and central contribution of NIHHL.
Christopher J Plack - One of the best experts on this subject based on the ideXlab platform.
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effects of age and noise exposure on proxy measures of cochlear Synaptopathy
Trends in hearing, 2019Co-Authors: Garreth Prendergast, Hannah Guest, Kevin J Munro, Karolina Kluk, Rebecca E Millman, Samuel Couth, Christopher J PlackAbstract:Although there is strong histological evidence for age-related Synaptopathy in humans, evidence for the existence of noise-induced cochlear Synaptopathy in humans is inconclusive. Here, we sought to evaluate the relative contributions of age and noise exposure to cochlear Synaptopathy using a series of electrophysiological and behavioral measures. We extended an existing cohort by including 33 adults in the age range 37 to 60, resulting in a total of 156 participants, with the additional older participants resulting in a weakening of the correlation between lifetime noise exposure and age. We used six independent regression models (corrected for multiple comparisons), in which age, lifetime noise exposure, and high-frequency audiometric thresholds were used to predict measures of Synaptopathy, with a focus on differential measures. The models for auditory brainstem responses, envelope-following responses, interaural phase discrimination, and the co-ordinate response measure of speech perception were not statistically significant. However, both age and noise exposure were significant predictors of performance on the digit triplet test of speech perception in noise, with greater noise exposure (unexpectedly) predicting better performance in the 80 dB sound pressure level (SPL) condition and greater age predicting better performance in the 40 dB SPL condition. Amplitude modulation detection thresholds were also significantly predicted by age, with older listeners performing better than younger listeners at 80 dB SPL. Overall, the results are inconsistent with the predicted effects of Synaptopathy.
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acoustic middle ear muscle reflex thresholds in humans with normal audiograms no relations to tinnitus speech perception in noise or noise exposure
Neuroscience, 2019Co-Authors: Hannah Guest, Kevin J Munro, Christopher J PlackAbstract:The acoustic middle-ear-muscle reflex (MEMR) has been suggested as a sensitive non-invasive measure of cochlear Synaptopathy, the loss of synapses between inner hair cells and auditory nerve fibers. In the present study, clinical MEMR thresholds were measured for 1-, 2-, and 4-kHz tonal elicitors, using a procedure shown to produce thresholds with excellent reliability. MEMR thresholds of 19 participants with tinnitus and normal audiograms were compared to those of 19 age- and sex-matched controls. MEMR thresholds did not differ significantly between the two groups at any frequency. These 38 participants were included in a larger sample of 70 participants with normal audiograms. For this larger group, MEMR thresholds were compared to a measure of spatial speech perception in noise (SPiN) and a detailed self-report estimate of lifetime noise exposure. MEMR thresholds were unrelated to either SPiN or noise exposure, despite a wide range in both measures. It is possible that thresholds measured using a clinical paradigm are less sensitive to Synaptopathy than those obtained using more sophisticated measurement techniques; however, we had good sensitivity at the group level, and even trends in the hypothesized direction were not observed. To the extent that MEMR thresholds are sensitive to cochlear Synaptopathy, the present results provide no evidence that tinnitus, SPiN, or noise exposure are related to Synaptopathy in the population studied.
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relations between speech perception in noise high frequency audiometry and physiological measures of cochlear Synaptopathy
Journal of the Acoustical Society of America, 2018Co-Authors: Hannah Guest, Kevin J Munro, Christopher J PlackAbstract:Cochlear Synaptopathy, a loss of synapses between inner hair cells and auditory nerve fibers, is associated with age and noise exposure in animal models. However, the functional consequences of Synaptopathy for humans are unclear. We pooled data from two recent studies to answer the question: are the common physiological measures of cochlear Synaptopathy related to speech-perception-in-noise (SPiN) performance? Eighty-three audiometrically normal participants (ages 18–39) took part. Measures of Synaptopathy were as follows: auditory brainstem response (ABR) wave I amplitude (102 dB peSPL click); ABR wave I:V amplitude ratio; envelope following response (EFR) amplitude (4 kHz carrier, 105 Hz modulation frequency); EFR amplitude growth with stimulus modulation depth; and middle ear muscle reflex threshold (1–4 kHz elicitors). We also conducted extended high-frequency (EHF) audiometry (10 and 14 kHz), suggested as a marker for Synaptopathy in lower frequency regions. SPiN performance was assessed using the coordinate response measure with spatial maskers. None of the physiological measures of Synaptopathy correlated significantly with SPiN. There was a significant correlation between EHF thresholds and SPiN, although it is unclear whether this is due to a direct relation between EHF hearing and SPiN, or whether elevated EHF thresholds are a marker for hidden damage at lower frequencies.
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reliability and interrelations of seven proxy measures of cochlear Synaptopathy
Journal of the Acoustical Society of America, 2018Co-Authors: Christopher J Plack, Hannah Guest, Kevin J MunroAbstract: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). Some metrics correlate with synaptic survival in animal models, but translation between species is not straightforward; measurements in humans likely 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 normally hearing young women underwent repeated measurements of ABR wave I amplitude, ABR wave I growth with level, ABR wave V latency shift in noise, EFR amplitude, EFR growth with stimulus modulation depth, MEMR threshold, and an MEMR difference measure. Intraclass correlation coefficients indicated good-to-excellent reliability for the raw ABR and EFR amplitudes, and for both MEMR measures. The ABR and EFR difference measures exhibited poor-to-moderate reliability. No significant correlations, nor any consistent trends, were observed between measures, providing no indication that the between-subject variability in responses are due to the same underlying physiological processes. Findings suggest that proxy measures of cochlear Synaptopathy should be regarded with caution, at least when employed in young, normally hearing adults.
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impaired speech perception in noise with a normal audiogram no evidence for cochlear Synaptopathy and no relation to lifetime noise exposure
Hearing Research, 2018Co-Authors: Hannah Guest, Kevin J Munro, Garreth Prendergast, Rebecca E Millman, Christopher J PlackAbstract:Abstract In rodents, noise exposure can destroy synapses between inner hair cells and auditory nerve fibers (“cochlear Synaptopathy”) without causing hair cell loss. Noise-induced cochlear Synaptopathy usually leaves cochlear thresholds unaltered, but is associated with long-term reductions in auditory brainstem response (ABR) amplitudes at medium-to-high sound levels. This pathophysiology has been suggested to degrade speech perception in noise (SPiN), perhaps explaining why SPiN ability varies so widely among audiometrically normal humans. The present study is the first to test for evidence of cochlear Synaptopathy in humans with significant SPiN impairment. Individuals were recruited on the basis of self-reported SPiN difficulties and normal pure tone audiometric thresholds. Performance on a listening task identified a subset with “verified” SPiN impairment. This group was matched with controls on the basis of age, sex, and audiometric thresholds up to 14 kHz. ABRs and envelope-following responses (EFRs) were recorded at high stimulus levels, yielding both raw amplitude measures and within-subject difference measures. Past exposure to high sound levels was assessed by detailed structured interview. Impaired SPiN was not associated with greater lifetime noise exposure, nor with any electrophysiological measure. It is conceivable that retrospective self-report cannot reliably capture noise exposure, and that ABRs and EFRs offer limited sensitivity to Synaptopathy in humans. Nevertheless, the results do not support the notion that noise-induced Synaptopathy is a significant etiology of SPiN impairment with normal audiometric thresholds. It may be that Synaptopathy alone does not have significant perceptual consequences, or is not widespread in humans with normal audiograms.
Sarah Verhulst - One of the best experts on this subject based on the ideXlab platform.
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the variability in potential biomarkers for cochlear Synaptopathy after recreational noise exposure
Journal of Speech Language and Hearing Research, 2021Co-Authors: Tine Vande Maele, Sarineh Keshishzadeh, Nele De Poortere, Ingeborg Dhooge, Hannah Keppler, Sarah VerhulstAbstract:Purpose Speech-in-noise tests and suprathreshold auditory evoked potentials are promising biomarkers to diagnose cochlear Synaptopathy (CS) in humans. This study investigated whether these biomarke...
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enhancing the sensitivity of the envelope following response for cochlear Synaptopathy screening in humans the role of stimulus envelope
Hearing Research, 2021Co-Authors: Viacheslav Vasilkov, Markus Garrett, Manfred Mauermann, Sarah VerhulstAbstract:Abstract Auditory de-afferentation, a permanent reduction in the number of inner-hair-cells and auditory-nerve synapses due to cochlear damage or Synaptopathy, can reliably be quantified using temporal bone histology and immunostaining. However, there is an urgent need for non-invasive markers of Synaptopathy to study its perceptual consequences in live humans and to develop effective therapeutic interventions. While animal studies have identified candidate auditory-evoked-potential (AEP) markers for Synaptopathy, their interpretation in humans has suffered from translational issues related to neural generator differences, unknown hearing-damage histopathologies or lack of measurement sensitivity. To render AEP-based markers of Synaptopathy more sensitive and differential to the Synaptopathy aspect of sensorineural hearing loss, we followed a combined computational and experimental approach. Starting from the known characteristics of auditory-nerve physiology, we optimized the stimulus envelope to stimulate the available auditory-nerve population optimally and synchronously to generate strong envelope-following-responses (EFRs). We further used model simulations to explore which stimuli evoked a response that was sensitive to Synaptopathy, while being maximally insensitive to possible co-existing outer-hair-cell pathologies. We compared the model-predicted trends to AEPs recorded in younger and older listeners (N=44, 24f) who had normal or impaired audiograms with suspected age-related Synaptopathy in the older cohort. We conclude that optimal stimulation paradigms for EFR-based quantification of Synaptopathy should have sharply rising envelope shapes, a minimal plateau duration of 1.7-2.1 ms for a 120-Hz modulation rate, and inter-peak intervals which contain near-zero amplitudes. From our recordings, the optimal EFR-evoking stimulus had a rectangular envelope shape with a 25% duty cycle and a 95% modulation depth. Older listeners with normal or impaired audiometric thresholds showed significantly reduced EFRs, which were consistent with how (age-induced) Synaptopathy affected these responses in the model.
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the variability in potential biomarkers for cochlear Synaptopathy after recreational noise exposure
bioRxiv, 2021Co-Authors: Tine Vande Maele, Sarineh Keshishzadeh, Nele De Poortere, Ingeborg Dhooge, Hannah Keppler, Sarah VerhulstAbstract:ABSTRACT Objectives Speech-in-noise tests and suprathreshold auditory evoked potentials are promising biomarkers to diagnose cochlear Synaptopathy (CS) in humans. This study investigated whether these biomarkers changed after recreational noise exposure. Design The baseline auditory status of 19 normal hearing young adults was analyzed using questionnaires, pure-tone audiometry, speech audiometry and auditory evoked potentials. Nineteen subjects attended a music festival and completed the same tests again at day 1, day 3 and day 5 after the music festival. Results No significant relations were found between lifetime noise-exposure history and the hearing tests. Changes in biomarkers from the first session to the follow-up sessions were non-significant, except for speech audiometry, that showed a significant training effect (performance improvement). Conclusions Despite the individual variability in pre-festival biomarkers, we did not observe changes related to the noise-exposure dose caused by the attended event. This can indicate the absence of noise-exposure-driven cochlear Synaptopathy in the study cohort, or reflect that biomarkers were not sensitive enough to detect mild CS. Future research should include a more diverse study cohort, dosimetry and results from test-retest reliability studies to provide more insight into the relationship between recreational noise exposure and cochlear Synaptopathy.
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speech in noise intelligibility difficulties with age the role of cochlear Synaptopathy
bioRxiv, 2020Co-Authors: Markus Garrett, Viacheslav Vasilkov, Manfred Mauermann, John L Wilson, Kenneth S Henry, Sarah VerhulstAbstract:Abstract Damage to auditory-nerve-fiber synapses (i.e. cochlear Synaptopathy) degrades the neural coding of sound and is predicted to impair sound perception in noisy listening environments. However, establishing a causal relationship between Synaptopathy and speech intelligibility is difficult because we have no direct access to synapse counts in humans. Hence, we rely on the quality of noninvasive auditory-evoked potential (AEP) markers developed in rodent studies of histologically-verified Synaptopathy. However, there are a number of reasons which render the interpretation of these markers in humans difficult. To bridge this translational gap, we apply a multi-method approach to enable a meaningful interpretation of the relationship between the histopathology of sensorineural hearing loss (SNHL) and speech perception. We first selected a Synaptopathy-sensitive AEP marker and verified its sensitivity (i) in an animal model using a Kainic-acid induced Synaptopathy, and (ii), via auditory model simulations which connect the histopathology of SNHL to the source generators of AEPs. Secondly, we restricted the frequency content of the speech-material to ensure that both AEP and speech metrics targeted similar cochlear frequency regions and associated auditory coding mechanisms. Following this approach, we studied the relative contribution of AEP markers of Synaptopathy and hearing sensitivity to speech recognition thresholds in 44 listeners (24 women) of different ages and SNHL profiles. Our analysis shows that Synaptopathy plays an important role for speech intelligibility in noise, but that outer-hair-cell integrity predicts performance in the absence of noise. Our results corroborate conclusions from animal studies regarding the prevalence of age-related Synaptopathy, and its occurrence before outer-hair-cell loss damage. Significance Statement Temporal-bone histology demonstrates that cochlear Synaptopathy, i.e. damage to inner-hair-cell auditory-nerve fiber synapses, sets in before sensory cell damage and associated hearing threshold elevation. Clinical practice assesses hearing status on the basis of audiometric thresholds, and is hence overlooking a -likely prevalent-aspect of sensorineural hearing damage given that ageing, noise exposure or ototoxic drugs can cause Synaptopathy. We present a multi-method approach to study the relationship between Synaptopathy and speech intelligibility and address an important unresolved issue in hearing science, namely why speech-intelligibility-in-noise degrades as we age, even when hearing sensitivity remains normal. Our study outcomes have important implications for hearing diagnostics and treatment.
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enhancing the sensitivity of the envelope following response for cochlear Synaptopathy screening in humans the role of stimulus envelope
bioRxiv, 2020Co-Authors: Viacheslav Vasilkov, Markus Garrett, Manfred Mauermann, Sarah VerhulstAbstract:Auditory de-afferentation, a permanent reduction in the number of inner-hair-cells and auditory-nerve synapses due to cochlear Synaptopathy or damage, can reliably be quantified using temporal bone histology and immunostaining. There is, however, an urgent need for non-invasive markers of Synaptopathy to study its perceptual consequences in live humans and to develop effective therapeutic interventions. While animal studies have identified candidate auditory-evoked-potential (AEP) based markers for Synaptopathy, their interpretation in humans has suffered from translational issues related to neural generator differences, unknown hearing-damage histopathologies or measurement sensitivity. To render AEP-based markers of Synaptopathy more robust and differential to the Synaptopathy aspect of sensorineural hearing loss, we followed a combined computational and experimental approach. Starting from the known characteristics of auditory-nerve physiology, we optimized the stimulus envelope for envelope-following-responses (EFRs) to optimally and synchronously stimulate the available auditory-nerve population and consequently generate a strong AEP. We additionally used model simulations to explore which stimuli evoked a response which was sensitive to Synaptopathy, while being insensitive to possible co-existing outer-hair-cell pathologies. We compared the model-predicted trends to AEPs recorded in younger and older listeners (N=44, 24f) who either had normal or impaired audiograms. We conclude that optimal stimulation paradigms for EFR-based quantification of Synaptopathy should have sharply rising envelope shapes, a minimal plateau duration of 1.7-2.1 ms for a 120 Hz modulation rate, and inter-peak intervals which contain near-zero amplitudes. From our recorded conditions, the optimal EFR-evoking stimulus had a rectangular envelope shape with a 25% duty cycle and a 95% modulation depth.
Kevin J Munro - One of the best experts on this subject based on the ideXlab platform.
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effects of age and noise exposure on proxy measures of cochlear Synaptopathy
Trends in hearing, 2019Co-Authors: Garreth Prendergast, Hannah Guest, Kevin J Munro, Karolina Kluk, Rebecca E Millman, Samuel Couth, Christopher J PlackAbstract:Although there is strong histological evidence for age-related Synaptopathy in humans, evidence for the existence of noise-induced cochlear Synaptopathy in humans is inconclusive. Here, we sought to evaluate the relative contributions of age and noise exposure to cochlear Synaptopathy using a series of electrophysiological and behavioral measures. We extended an existing cohort by including 33 adults in the age range 37 to 60, resulting in a total of 156 participants, with the additional older participants resulting in a weakening of the correlation between lifetime noise exposure and age. We used six independent regression models (corrected for multiple comparisons), in which age, lifetime noise exposure, and high-frequency audiometric thresholds were used to predict measures of Synaptopathy, with a focus on differential measures. The models for auditory brainstem responses, envelope-following responses, interaural phase discrimination, and the co-ordinate response measure of speech perception were not statistically significant. However, both age and noise exposure were significant predictors of performance on the digit triplet test of speech perception in noise, with greater noise exposure (unexpectedly) predicting better performance in the 80 dB sound pressure level (SPL) condition and greater age predicting better performance in the 40 dB SPL condition. Amplitude modulation detection thresholds were also significantly predicted by age, with older listeners performing better than younger listeners at 80 dB SPL. Overall, the results are inconsistent with the predicted effects of Synaptopathy.
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acoustic middle ear muscle reflex thresholds in humans with normal audiograms no relations to tinnitus speech perception in noise or noise exposure
Neuroscience, 2019Co-Authors: Hannah Guest, Kevin J Munro, Christopher J PlackAbstract:The acoustic middle-ear-muscle reflex (MEMR) has been suggested as a sensitive non-invasive measure of cochlear Synaptopathy, the loss of synapses between inner hair cells and auditory nerve fibers. In the present study, clinical MEMR thresholds were measured for 1-, 2-, and 4-kHz tonal elicitors, using a procedure shown to produce thresholds with excellent reliability. MEMR thresholds of 19 participants with tinnitus and normal audiograms were compared to those of 19 age- and sex-matched controls. MEMR thresholds did not differ significantly between the two groups at any frequency. These 38 participants were included in a larger sample of 70 participants with normal audiograms. For this larger group, MEMR thresholds were compared to a measure of spatial speech perception in noise (SPiN) and a detailed self-report estimate of lifetime noise exposure. MEMR thresholds were unrelated to either SPiN or noise exposure, despite a wide range in both measures. It is possible that thresholds measured using a clinical paradigm are less sensitive to Synaptopathy than those obtained using more sophisticated measurement techniques; however, we had good sensitivity at the group level, and even trends in the hypothesized direction were not observed. To the extent that MEMR thresholds are sensitive to cochlear Synaptopathy, the present results provide no evidence that tinnitus, SPiN, or noise exposure are related to Synaptopathy in the population studied.
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relations between speech perception in noise high frequency audiometry and physiological measures of cochlear Synaptopathy
Journal of the Acoustical Society of America, 2018Co-Authors: Hannah Guest, Kevin J Munro, Christopher J PlackAbstract:Cochlear Synaptopathy, a loss of synapses between inner hair cells and auditory nerve fibers, is associated with age and noise exposure in animal models. However, the functional consequences of Synaptopathy for humans are unclear. We pooled data from two recent studies to answer the question: are the common physiological measures of cochlear Synaptopathy related to speech-perception-in-noise (SPiN) performance? Eighty-three audiometrically normal participants (ages 18–39) took part. Measures of Synaptopathy were as follows: auditory brainstem response (ABR) wave I amplitude (102 dB peSPL click); ABR wave I:V amplitude ratio; envelope following response (EFR) amplitude (4 kHz carrier, 105 Hz modulation frequency); EFR amplitude growth with stimulus modulation depth; and middle ear muscle reflex threshold (1–4 kHz elicitors). We also conducted extended high-frequency (EHF) audiometry (10 and 14 kHz), suggested as a marker for Synaptopathy in lower frequency regions. SPiN performance was assessed using the coordinate response measure with spatial maskers. None of the physiological measures of Synaptopathy correlated significantly with SPiN. There was a significant correlation between EHF thresholds and SPiN, although it is unclear whether this is due to a direct relation between EHF hearing and SPiN, or whether elevated EHF thresholds are a marker for hidden damage at lower frequencies.
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reliability and interrelations of seven proxy measures of cochlear Synaptopathy
Journal of the Acoustical Society of America, 2018Co-Authors: Christopher J Plack, Hannah Guest, Kevin J MunroAbstract: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). Some metrics correlate with synaptic survival in animal models, but translation between species is not straightforward; measurements in humans likely 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 normally hearing young women underwent repeated measurements of ABR wave I amplitude, ABR wave I growth with level, ABR wave V latency shift in noise, EFR amplitude, EFR growth with stimulus modulation depth, MEMR threshold, and an MEMR difference measure. Intraclass correlation coefficients indicated good-to-excellent reliability for the raw ABR and EFR amplitudes, and for both MEMR measures. The ABR and EFR difference measures exhibited poor-to-moderate reliability. No significant correlations, nor any consistent trends, were observed between measures, providing no indication that the between-subject variability in responses are due to the same underlying physiological processes. Findings suggest that proxy measures of cochlear Synaptopathy should be regarded with caution, at least when employed in young, normally hearing adults.
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impaired speech perception in noise with a normal audiogram no evidence for cochlear Synaptopathy and no relation to lifetime noise exposure
Hearing Research, 2018Co-Authors: Hannah Guest, Kevin J Munro, Garreth Prendergast, Rebecca E Millman, Christopher J PlackAbstract:Abstract In rodents, noise exposure can destroy synapses between inner hair cells and auditory nerve fibers (“cochlear Synaptopathy”) without causing hair cell loss. Noise-induced cochlear Synaptopathy usually leaves cochlear thresholds unaltered, but is associated with long-term reductions in auditory brainstem response (ABR) amplitudes at medium-to-high sound levels. This pathophysiology has been suggested to degrade speech perception in noise (SPiN), perhaps explaining why SPiN ability varies so widely among audiometrically normal humans. The present study is the first to test for evidence of cochlear Synaptopathy in humans with significant SPiN impairment. Individuals were recruited on the basis of self-reported SPiN difficulties and normal pure tone audiometric thresholds. Performance on a listening task identified a subset with “verified” SPiN impairment. This group was matched with controls on the basis of age, sex, and audiometric thresholds up to 14 kHz. ABRs and envelope-following responses (EFRs) were recorded at high stimulus levels, yielding both raw amplitude measures and within-subject difference measures. Past exposure to high sound levels was assessed by detailed structured interview. Impaired SPiN was not associated with greater lifetime noise exposure, nor with any electrophysiological measure. It is conceivable that retrospective self-report cannot reliably capture noise exposure, and that ABRs and EFRs offer limited sensitivity to Synaptopathy in humans. Nevertheless, the results do not support the notion that noise-induced Synaptopathy is a significant etiology of SPiN impairment with normal audiometric thresholds. It may be that Synaptopathy alone does not have significant perceptual consequences, or is not widespread in humans with normal audiograms.
Sharon G Kujawa - One of the best experts on this subject based on the ideXlab platform.
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trk agonist drugs rescue noise induced hidden hearing loss
JCI insight, 2021Co-Authors: Katharine A Fernandez, Sharon G Kujawa, Mingjie Tong, Takahisa Watabe, Xiankai Meng, Kohsuke Tani, Albert S B EdgeAbstract:TrkB agonist drugs are shown here to have a significant effect on the regeneration of afferent cochlear synapses after noise-induced Synaptopathy. The effects were consistent with regeneration of cochlear synapses that we observed in vitro after synaptic loss due to kainic acid-induced glutamate toxicity and were elicited by administration of TrkB agonists, amitriptyline, and 7,8-dihydroxyflavone, directly into the cochlea via the posterior semicircular canal 48 hours after exposure to noise. Synaptic counts at the inner hair cell and wave 1 amplitudes in the auditory brainstem response (ABR) were partially restored 2 weeks after drug treatment. Effects of amitriptyline on wave 1 amplitude and afferent auditory synapse numbers in noise-exposed ears after systemic (as opposed to local) delivery were profound and long-lasting; synapses in the treated animals remained intact 1 year after the treatment. However, the effect of systemically delivered amitriptyline on synaptic rescue was dependent on dose and the time window of administration: it was only effective when given before noise exposure at the highest injected dose. The long-lasting effect and the efficacy of postexposure treatment indicate a potential broad application for the treatment of Synaptopathy, which often goes undetected until well after the original damaging exposures.
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noise induced cochlear Synaptopathy with and without sensory cell loss
Neuroscience, 2020Co-Authors: Katharine A Fernandez, Dan Guo, Steven Micucci, Victor De Gruttola, Charles M Liberman, Sharon G KujawaAbstract:Abstract Prior work has provided extensive documentation of threshold sensitivity and sensory hair cell losses after noise exposure. It is now clear, however, that cochlear synaptic loss precedes such losses, at least at low-moderate noise doses, silencing affected neurons. To address questions of whether, and how, cochlear Synaptopathy and underlying mechanisms change as noise dose is varied, we assessed cochlear physiologic and histologic consequences of a range of exposures varied in duration from 15 min to 8 h and in level from 85 to 112 dB SPL. Exposures delivered to adult CBA/CaJ mice produced acute elevations in hair cell- and neural-based response thresholds ranging from trivial (∼5 dB) to large (∼50 dB), followed by varying degrees of recovery. Males appeared more noise vulnerable for some conditions of exposure. There was little to no inner hair cell (IHC) loss, but outer hair cell (OHC) loss could be substantial at highest frequencies for highest noise doses. Synapse loss was an early manifestation of noise injury and did not scale directly with either temporary or permanent threshold shift. With increasing noise dose, synapse loss grew to ∼50%, then declined for exposures yielding permanent hair cell injury/loss. All synaptopathic, but no non-synaptopathic exposures produced persistent neural response amplitude declines; those additionally yielding permanent OHC injury/loss also produced persistent reductions in OHC-based responses and exaggerated neural amplitude declines. Findings show that widespread cochlear Synaptopathy can be present with and without noise-induced sensory cell loss and that differing patterns of cellular injury influence synaptopathic outcomes.
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Synaptopathy in the aging cochlea characterizing early neural deficits in auditory temporal envelope processing
The Journal of Neuroscience, 2018Co-Authors: Aravindakshan Parthasarathy, Sharon G KujawaAbstract:Aging listeners, even in the absence of overt hearing loss measured as changes in hearing thresholds, often experience impairments processing temporally complex sounds such as speech in noise. Recent evidence has shown that normal aging is accompanied by a progressive loss of synapses between inner hair cells and auditory nerve fibers. The role of this cochlear Synaptopathy in degraded temporal processing with age is not yet understood. Here, we used population envelope following responses, along with other hair cell- and neural-based measures from an age-graded series of male and female CBA/CaJ mice to study changes in encoding stimulus envelopes. By comparing responses obtained before and after the application of the neurotoxin ouabain to the inner ear, we demonstrate that we can study changes in temporal processing on either side of the cochlear synapse. Results show that deficits in neural coding with age emerge at the earliest neural stages of auditory processing and are correlated with the degree of cochlear Synaptopathy. These changes are seen before losses in neural thresholds and particularly affect the suprathreshold processing of sound. Responses obtained from more central sources show smaller differences with age, suggesting compensatory gain. These results show that progressive cochlear Synaptopathy is accompanied by deficits in temporal coding at the earliest neural generators and contribute to the suprathreshold sound processing deficits observed with age.SIGNIFICANCE STATEMENT Aging listeners often experience difficulty hearing and understanding speech in noisy conditions. The results described here suggest that age-related loss of cochlear synapses may be a significant contributor to those performance declines. We observed aberrant neural coding of sounds in the early auditory pathway, which was accompanied by and correlated with an age-progressive loss of synapses between the inner hair cells and the auditory nerve. Deficits first appeared before changes in hearing thresholds and were largest at higher sound levels relevant to real world communication. The noninvasive tests described here may be adapted to detect cochlear Synaptopathy in the clinical setting.
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aging after noise exposure acceleration of cochlear Synaptopathy in recovered ears
The Journal of Neuroscience, 2015Co-Authors: Katharine A Fernandez, Charles M Liberman, Sharon G Kujawa, Penelope W C Jeffers, Kumud LallAbstract:Cochlear synaptic loss, rather than hair cell death, is the earliest sign of damage in both noise- and age-related hearing impairment (Kujawa and Liberman, 2009; Sergeyenko et al., 2013). Here, we compare cochlear aging after two types of noise exposure: one producing permanent synaptic damage without hair cell loss and another producing neither Synaptopathy nor hair cell loss. Adult mice were exposed (8–16 kHz, 100 or 91 dB SPL for 2 h) and then evaluated from 1 h to ∼20 months after exposure. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses (ABRs). Cochlear whole mounts and plastic sections were studied to quantify hair cells, cochlear neurons, and the synapses connecting them. The synaptopathic noise (100 dB) caused 35–50 dB threshold shifts at 24 h. By 2 weeks, thresholds had recovered, but synaptic counts and ABR amplitudes at high frequencies were reduced by up to ∼45%. As exposed animals aged, Synaptopathy was exacerbated compared with controls and spread to lower frequencies. Proportional ganglion cell losses followed. Threshold shifts first appeared >1 year after exposure and, by ∼20 months, were up to 18 dB greater in the synaptopathic noise group. Outer hair cell losses were exacerbated in the same time frame (∼10% at 32 kHz). In contrast, the 91 dB exposure, producing transient threshold shift without acute Synaptopathy, showed no acceleration of synaptic loss or cochlear dysfunction as animals aged, at least to ∼1 year after exposure. Therefore, interactions between noise and aging may require an acute Synaptopathy, but a single synaptopathic exposure can accelerate cochlear aging.
