scholarly journals Envelope Following Response Measurements in Young Veterans Are Consistent With Noise-Induced Cochlear Synaptopathy

2020 ◽  
Author(s):  
Naomi Bramhall ◽  
Garnett McMillan ◽  
Sean Kampel

Animal studies have demonstrated that noise exposure can lead to the loss of the synapses between the inner hair cells and their afferent auditory nerve fiber targets without impacting auditory thresholds. Although several non-invasive physiological measures appear to be sensitive to cochlear synaptopathy in animal models, including auditory brainstem response (ABR) wave I amplitude, the envelope following response (EFR), and the middle ear muscle reflex (MEMR), human studies of these measures in samples that are expected to vary in terms of the degree of noise-induced synaptopathy have resulted in mixed findings. One possible explanation for the differing results is that synaptopathy risk is lower for recreational noise exposure than for occupational or military noise exposure. The goal of this analysis was to determine if EFR magnitude and ABR wave I amplitude are reduced among young Veterans with a history of military noise exposure compared with non-Veteran controls with minimal noise exposure. EFRs and ABRs were obtained in a sample of young (19-35 years) Veterans and non-Veterans with normal audiograms and robust distortion product otoacoustic emissions (DPOAEs). Mean EFR magnitudes and ABR wave I amplitudes were reduced for Veterans compared with non-Veteran controls. These findings replicate previous ABR wave I amplitude results in young Veterans and are consistent with animal models of noise-induced cochlear synaptopathy.

2020 ◽  
Vol 29 (2) ◽  
pp. 152-164 ◽  
Author(s):  
Naomi F. Bramhall ◽  
Christopher E. Niemczak ◽  
Sean D. Kampel ◽  
Curtis J. Billings ◽  
Garnett P. McMillan

Purpose Complaints of auditory perceptual deficits, such as tinnitus and difficulty understanding speech in background noise, among individuals with clinically normal audiograms present a perplexing problem for audiologists. One potential explanation for these “hidden” auditory deficits is loss of the synaptic connections between the inner hair cells and their afferent auditory nerve fiber targets, a condition that has been termed cochlear synaptopathy . In animal models, cochlear synaptopathy can occur due to aging or exposure to noise or ototoxic drugs and is associated with reduced auditory brainstem response (ABR) wave I amplitudes. Decreased ABR wave I amplitudes have been demonstrated among young military Veterans and non-Veterans with a history of firearm use, suggesting that humans may also experience noise-induced synaptopathy. However, the downstream consequences of synaptopathy are unclear. Method To investigate how noise-induced reductions in wave I amplitude impact the central auditory system, the ABR, the middle latency response (MLR), and the late latency response (LLR) were measured in 65 young Veterans and non-Veterans with normal audiograms. Results In response to a click stimulus, the MLR was weaker for Veterans compared to non-Veterans, but the LLR was not reduced. In addition, low ABR wave I amplitudes were associated with a reduced MLR, but with an increased LLR. Notably, Veterans reporting tinnitus showed the largest mean LLRs. Conclusions These findings indicate that decreased peripheral auditory input leads to compensatory gain in the central auditory system, even among individuals with normal audiograms, and may impact auditory perception. This pattern of reduced MLR, but not LLR, was observed among Veterans even after statistical adjustment for sex and distortion product otoacoustic emission differences, suggesting that synaptic loss plays a role in the observed central gain. Supplemental Material https://doi.org/10.23641/asha.11977854


2019 ◽  
Author(s):  
Naomi Bramhall ◽  
Garnett McMillan ◽  
Frederick Gallun ◽  
Dawn Konrad-Martin

Tinnitus is one of the predicted perceptual consequences of cochlear synaptopathy, a type of age-, noise-, or drug-induced auditory damage that has been demonstrated in animal models to cause homeostatic changes in central auditory gain. Although synaptopathy has been observed in human temporal bones, assessment of this condition in living humans is limited to indirect non-invasive measures such as the auditory brainstem response (ABR). In animal models, synaptopathy is associated with a reduction in ABR wave I amplitude at suprathreshold stimulus levels. Several human studies have explored the relationship between wave I amplitude and tinnitus, with conflicting results. This study investigates the hypothesis that reduced peripheral auditory input due to synaptic/neuronal loss is associated with tinnitus. ABR wave I amplitude data from 193 individuals (43 with tinnitus (22%), 150 without tinnitus (78%)), who participated in up to three out of four different studies, were included in a logistic regression analysis to estimate the relationship between wave I amplitude and tinnitus at a variety of stimulus levels and frequencies. Statistical adjustment for sex and distortion product otoacoustic emissions was included in the analysis. The results suggest that smaller ABR wave I amplitudes are associated with an increased probability of reporting tinnitus.


2020 ◽  
Author(s):  
Brad N. Buran ◽  
Garnett McMillan ◽  
Sarineh Keshishzadeh ◽  
Sarah Verhulst ◽  
Naomi Bramhall

Aging, noise exposure, and ototoxic medications lead to cochlear synapse loss in animal models. As cochlear function is highly conserved across mammalian species, synaptopathy likely occurs in humans as well. Indeed, temporal bone studies demonstrate loss of synapses with advancing age in humans. Synaptopathy is predicted to result in perceptual deficits including tinnitus, hyperacusis, and difficulty understanding speech-in-noise. However, there is currently no method for diagnosing synaptopathy in living humans. This prevents us from determining if noise-induced synaptopathy occurs in humans, identifying the perceptual consequences of synaptopathy, or testing potential drug treatments. Several physiological measures are sensitive to synaptopathy in animal models, including auditory brainstem response (ABR) wave I amplitude. However, it is unclear how to translate these measures to synaptopathy diagnosis in humans. In this study, a human computational model of the auditory periphery that can predict ABR waveforms and distortion product otoacoustic emissions (DPOAEs) was fit using Bayesian regression analysis to predict synapse counts in individual human participants based on their measured DPOAE levels and ABR wave I amplitudes. Lower predicted synapse numbers were associated with higher noise exposure history, increased likelihood of tinnitus, and poorer speech-in-noise perception. These findings illustrate the utility of this modeling approach in predicting synapse counts from physiological data.


1994 ◽  
Vol 110 (1) ◽  
pp. 22-38 ◽  
Author(s):  
James W. Hall ◽  
Jane E. Baer ◽  
Patricia A. Chase ◽  
Mitchell K. Schwaber

Three electrophysiologic audiologic procedures-aural immittance measurement, auditory brainstem response (ABR), and otoacoustic emissions (OAE) — were first described in the 1970's. Immittance measurement and ABR have contributed importantly for years to the assessment of auditory function in children and adults, whereas OAEs have not yet been incorporated into the everyday audiology test battery. In this article, we argue that the transition from OAE measurement by hearing scientists in laboratory settings to routine application by audiologists in the clinic will be greatly facilitated by (1) comprehensive, large-scale studies of the effects of subject characteristics, such as gender and age (from infancy to advancing adulthood), on both transient evoked (TEOAE) and distortion product (DPOAE) otoacoustic emissions; (2) clinical investigations of TEOAE and DPOAE in sizeable patient populations with specific neurotologic diagnoses; (3) guidelines for OAE test protocols in clinical environments; and (4) clear criteria for OAE analysis in clinical populations.


2020 ◽  
Vol 19 (2) ◽  
pp. 299-304
Author(s):  
Dejun Zhang ◽  
Guofang Guan ◽  
Yingyuan Guo ◽  
Yanru Hao ◽  
Fang Guo ◽  
...  

Purpose: To determine the protective effect of ethosuximide on the hearing of NOD/LtJ mice, and the underlying mechanism of action. Methods: The mice were randomly assigned to control and treatment groups (20 mice per group). Mice in the treatment group were administered ethosuximide intraperitoneally at a dose of 200mg/kg body weight (bwt), while those in the control group received an equivalent dose of saline via the same route. Both groups were subjected to auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) tests, as well as determination of mRNA expressions of α1G, α1H, α1I, m-calpain, μ-calpain, and caspase-3. Results: At ages of 6 and 9 weeks, ABR values were significantly lower in the treatment group than those in the control group (p < 0.05). At age 3, 6 and 9 weeks, control group DPOAE values were much lower than those in the treatment group. However, at signal frequency of 35344 Hz, DPOAE value was significantly reduced in the treatment group (p < 0.05). There was significant down-regulation in mRNA expressions of α1G, α1H, α1I, m-calpain, μ-calpain and caspase-3, in the treatment group, when compared with the control group (p < 0.05). Conclusion: Ethosuximide delays mice hearing loss and protects their hearing via a mechanism involving blockage of endogenous apoptotic pathways. This mechanism may provide guidance in the search for suitable new drugs. Keywords: Ethosuximide, Endogenous apoptosis, Hearing, Protection


2021 ◽  
Author(s):  
Naomi Bramhall ◽  
Kelly M. Reavis ◽  
M. Patrick Feeney ◽  
Sean Kampel

Noise-induced cochlear synaptopathy, the loss of the synaptic connections between inner hair cells and afferent auditory nerve fibers, has been demonstrated in multiple animal models, including non-human primates. However, given that synaptopathy can only be confirmed with post-mortem temporal bone analysis, it has been difficult to determine whether noise-induced synaptopathy occurs in humans. Human studies of noise-induced synaptopathy using physiological indicators identified in animal models (auditory brainstem response [ABR] wave I amplitude, the envelope following response [EFR], and the middle ear muscle reflex [MEMR]) have yielded mixed findings. Differences in the population studied may have contributed to the differing results. For example, due to differences in the intensity level of the noise exposure, noise-induced synaptopathy may be easier to detect in a military Veteran population than in populations with recreational noise exposure. We previously demonstrated a reduction in ABR wave I amplitude and EFR magnitude for young Veterans with normal audiograms reporting high levels of noise exposure compared to non-Veteran controls. In this report, we expand on the previous analysis in the same population to determine if MEMR magnitude is similarly reduced. The results of the statistical analysis, although not conventionally statistically significant, suggest a reduction in mean MEMR magnitude for Veterans reporting high noise exposure compared with non-Veteran controls. In addition, the MEMR appears relatively insensitive to subclinical outer hair cell dysfunction and is not well correlated with ABR and EFR measurements. When combined with our previous ABR and EFR findings in the same population, these results suggest that noise-induced synaptopathy occurs in humans. In addition, the findings indicate that the MEMR may be a good candidate for non-invasive diagnosis of cochlear synaptopathy/deafferentation and that the MEMR may reflect the integrity of different neural populations than the ABR and EFR.


Author(s):  
Ö Gedik ◽  
H Hüsam ◽  
M Başöz ◽  
N Tas ◽  
F Aksoy

Abstract Objective This study aimed to evaluate different auditory regions with audiological tests, based on the presumption that there may be damage to the structures in the hearing system after coronavirus disease 2019. Methods Twenty individuals with no history of coronavirus disease 2019 and 27 individuals diagnosed with coronavirus disease 2019 were compared. Pure tone, speech and extended high-frequency audiometry, acoustic immitansmetry, transient evoked and distortion product otoacoustic emissions testing, and auditory brainstem response testing were conducted. Results The pure tone audiometry and extended high-frequency mean threshold values were higher in the coronavirus disease 2019 group. The transient evoked otoacoustic emissions signal-to-noise ratios were bilaterally lower at 4 kHz in individuals with a coronavirus disease 2019 history. In the auditory brainstem response test, only the interpeak latencies of waves III–V were significantly different between groups. Conclusion Coronavirus disease 2019 may cause damage to the hearing system. Patients should be followed up in the long term with advanced audiological evaluation methods in order to determine the extent and level of damage.


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