The Physiological Bases of Hidden Noise-Induced Hearing Loss: Protocol for a Functional Neuroimaging Study (Preprint)

BACKGROUND Rodent studies indicate that noise exposure can cause permanent damage to synapses between inner hair cells and high-threshold auditory nerve fibers, without permanently altering threshold sensitivity. These demonstrations of what is commonly known as hidden hearing loss have been confirmed in several rodent species, but the implications for human hearing are unclear. OBJECTIVE Our Medical Research Council–funded program aims to address this unanswered question, by investigating functional consequences of the damage to the human peripheral and central auditory nervous system that results from cumulative lifetime noise exposure. Behavioral and neuroimaging techniques are being used in a series of parallel studies aimed at detecting hidden hearing loss in humans. The planned neuroimaging study aims to (1) identify central auditory biomarkers associated with hidden hearing loss; (2) investigate whether there are any additive contributions from tinnitus or diminished sound tolerance, which are often comorbid with hearing problems; and (3) explore the relation between subcortical functional magnetic resonance imaging (fMRI) measures and the auditory brainstem response (ABR). METHODS Individuals aged 25 to 40 years with pure tone hearing thresholds ≤20 dB hearing level over the range 500 Hz to 8 kHz and no contraindications for MRI or signs of ear disease will be recruited into the study. Lifetime noise exposure will be estimated using an in-depth structured interview. Auditory responses throughout the central auditory system will be recorded using ABR and fMRI. Analyses will focus predominantly on correlations between lifetime noise exposure and auditory response characteristics. RESULTS This paper reports the study protocol. The funding was awarded in July 2013. Enrollment for the study described in this protocol commenced in February 2017 and was completed in December 2017. Results are expected in 2018. CONCLUSIONS This challenging and comprehensive study will have the potential to impact diagnostic procedures for hidden hearing loss, enabling early identification of noise-induced auditory damage via the detection of changes in central auditory processing. Consequently, this will generate the opportunity to give personalized advice regarding provision of ear defense and monitoring of further damage, thus reducing the incidence of noise-induced hearing loss.

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Morphology Changes in the Cochlea of Impulse Noiseinduced Hidden Hearing Loss

10.21203/rs.3.rs-961609/v1 ◽

2021 ◽

Author(s):

Guo-wei Qi ◽

Lei Shi ◽

Han-dai Qin ◽

Yuhua Zhu ◽

Qing-qing Jiang ◽

...

Keyword(s):

Hearing Loss ◽

Guinea Pigs ◽

Impulse Noise ◽

Noise Exposure ◽

Nerve Fibers ◽

Basement Membranes ◽

Time Interval ◽

Noise Induced Hearing Loss ◽

Hidden Hearing Loss ◽

Morphology Changes

Abstract Objectives: This study was designed to determine the morphology changes of noise-induced hidden hearing loss (NIHHL). Method: Fifteen guinea pigs were divided into three groups: noise-induced hidden hearing loss (NIHHL) group, noise-induced hearing loss (NIHL) group, and normal control group. For the noise-induced hidden hearing loss group, the guinea pigs were exposed to 15 times of impulse noise at one time. For the noise-induced hearing loss group, the animals were exposed to a total of 200 times of impulse noise in two times, and the time interval is 24 hours. Auditory brain response (ABR) was tested before, immediately, 24h, 1week, and one month after noise exposure to evaluate cochlear physiology changes. One month after noise exposure, all guinea pigs in three groups were sacrificed, and basement membranes were carefully dissected immediately after ABR tests. The cochlea samples were observed by transmission electron microscopy (TEM) to found out the monograph changes. Result: The ABR results showed that 15 times of impulse noise exposure could cause NIHHL in guinea pigs and 200 times could cause completely hearing loss. Impulse noise exposure could cause a dramatic increase in chondriosome in the inner hair cell. The structures of ribbon synapses and heminodes were also obviously impaired compared to the normal group. The nerve fibers and myelin sheaths remained intact after impulse noise exposure. Conclusion: This research revealed for the first time that impulse noise could cause hidden hearing loss, and the changes in inner hair cells, ribbon synapse, and heminode all played a vital role in the pathogenesis of hidden hearing loss.

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Effect of Phlorofucofuroeckol A and Dieckol Extracted from Ecklonia cava on Noise-induced Hearing Loss in a Mouse Model

Marine Drugs ◽

10.3390/md19080443 ◽

2021 ◽

Vol 19 (8) ◽

pp. 443

Author(s):

Hyunjun Woo ◽

Min-Kyung Kim ◽

Sohyeon Park ◽

Seung-Hee Han ◽

Hyeon-Cheol Shin ◽

...

Keyword(s):

Hearing Loss ◽

Hair Cell ◽

Noise Exposure ◽

Radical Scavenging ◽

Threshold Shift ◽

Ecklonia Cava ◽

Control Group ◽

Noise Induced Hearing Loss ◽

Antioxidant Agents ◽

Brainstem Response

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

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Noise Exposure and Hearing Threshold Profile among Zumba Fitness Regulars in Kuantan, Pahang, Malaysia

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v19i2.1566 ◽

2020 ◽

Vol 19 (2) ◽

Author(s):

Razali A ◽

Othman MS ◽

Rahman MS ◽

Misaridin NFI

Keyword(s):

Hearing Loss ◽

Noise Exposure ◽

Hearing Threshold ◽

Sound Level ◽

Hearing Level ◽

Noise Induced Hearing Loss ◽

Loud Noise ◽

Abnormal Pattern ◽

Level Meter ◽

Hearing System

INTRODUCTION: Recreational noise exposure has become a major threat to the hearing system, and this includes exposure to loud noise during group exercises such as Zumba Fitness, where loud music plays an important role. This study aimed to assess the noise exposure and hearing threshold profile among Zumba Fitness regulars in Kuantan, Malaysia. MATERIALS AND METHODS: Noise exposure and hearing profile threshold were measured during Zumba Fitness sessions at a fitness studio in Kuantan, Malaysia from 24th June 2014 to 12th August 2014. Noise exposure was measured using a noise dosimeter for one hour of Zumba Fitness session with a total of nine sessions run by three different instructors while sound level pressure was taken using a sound level meter during ambient, peak session and during cooling down. Thirty participants answered questionnaires and underwent pure tone diagnostic audiometry test at a local clinic for hearing threshold documentation. RESULTS: Some areas of the hall posed higher risks of causing noise-induced hearing loss especially near the amplifiers. There were periods when the hearing level exceeded 115 dBA. Early abnormal pattern could be observed in the hearing profiles of some of the participants to suggest preliminary hearing problems. CONCLUSION: Zumba Fitness regulars have a risk of developing noise-induced hearing loss and preventive steps should be properly addressed as NIHL is permanent and irreversible.

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Effect of Specific Retinoic Acid Receptor Agonists on Noise-Induced Hearing Loss

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16183428 ◽

2019 ◽

Vol 16 (18) ◽

pp. 3428 ◽

Cited By ~ 1

Author(s):

Sang Hyun Kwak ◽

Gi-Sung Nam ◽

Seong Hoon Bae ◽

Jinsei Jung

Keyword(s):

Hearing Loss ◽

Retinoic Acid ◽

Noise Exposure ◽

Retinoic Acid Receptor ◽

Protective Effects ◽

Noise Induced Hearing Loss ◽

Acid Receptor ◽

Significant Difference ◽

Brainstem Response ◽

Selective Agonists

Noise is one of the most common causes of hearing loss in industrial countries. There are many studies about chemical agents to prevent noise-induced hearing loss (NIHL). However, there is no commercially available drug yet. Retinoic acid is an active metabolite of Vitamin A; it has an anti-apoptic role in NIHL. This study aims to verify the differences among selective agonists of retinoic acid receptors (RARs) in NIHL. All-trans retinoic acid (ATRA), AM80 (selective retinoic acid receptor α agonist), AC261066 (Selective retinoic acid receptor β1 agonist), and CD1530 (Selective retinoic acid λ agonist) were injected to 6–7 weeks old CJ5BL/6 mice before noise (110 dB for 3 h) exposure. In the auditory brainstem response test pre-, post 1, 3, and 7 days after noise exposure, not only ATRA but all kinds of selective RAR agonists showed protective effects in hearing threshold and wave I amplitude. Though there was no significant difference in the level of protective effects between agonists, α agonist showed the most prominent effect in preserving hearing function as well as outer hair cells after noise exposure. In conclusion, selective agonists of RAR demonstrate comparable protective effects against NIHL to retinoic acid. Given that these selective RAR agonists have less side effects than retinoic acid, they may be promising potential drugs against NIHL.

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Effects of D-methionine in mice with noise-induced hearing loss mice

Journal of International Medical Research ◽

10.1177/0300060519860679 ◽

2019 ◽

Vol 47 (8) ◽

pp. 3874-3885 ◽

Cited By ~ 2

Author(s):

Yanru Wang ◽

Yan Qu ◽

Xuzhen Chen ◽

Pu Zhang ◽

Dan Su ◽

...

Keyword(s):

Hearing Loss ◽

Basement Membrane ◽

Mouse Model ◽

Hair Cells ◽

Noise Exposure ◽

Stria Vascularis ◽

Connexin 26 ◽

Noise Induced Hearing Loss ◽

Expression Levels ◽

Brainstem Response

Objective To study the effects of D-methionine in a mouse model of noise-induced hearing loss (NIHL). Methods We investigated changes in auditory function and microscopic cochlear structure in a mouse model of NIHL, and carried out 4-hydroxynonenal (4-HNE) immunostaining and terminal deoxynucleotidyl transferase dUTP nick-end labeling, and examined expression levels of connexins 26 and 30 by western blot. Results The auditory brainstem response threshold was significantly increased by noise exposure. Noise exposure also damaged the inner and particularly the outer hair cells in the cochlear basement membrane, while histochemistry demonstrated only scattered loss of hair cells in the basement membrane in mice treated with D-methionine before or after noise exposure. D-methionine inhibited apoptosis in the cochlear basement membrane, stria vascularis, and spiral ligament. 4-HNE expression in the basement membrane, stria vascularis, and spiral collateral ligament was increased by noise exposure, but this increase was attenuated by D-methionine. Connexin 26 and connexin 30 expression levels were reduced by noise exposure, and this effect was similarly attenuated by D-methionine administered either before or after noise exposure. Conclusion D-methionine administered before or after noise exposure could rescue NIHL by protecting cochlear morphology, inhibiting apoptosis, and maintaining connexin 26 and 30 expression.

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Impulse Noise Induced Hidden Hearing Loss, Hair Cell Ciliary Changes and Oxidative Stress in Mice

Antioxidants ◽

10.3390/antiox10121880 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1880

Author(s):

Paul Gratias ◽

Jamal Nasr ◽

Corentin Affortit ◽

Jean-Charles Ceccato ◽

Florence François ◽

...

Keyword(s):

Oxidative Stress ◽

Hearing Loss ◽

Hair Cells ◽

Impulse Noise ◽

Noise Exposure ◽

Morphological Changes ◽

Nerve Fibers ◽

Outer Hair Cells ◽

Hidden Hearing Loss ◽

The Impact

Recent studies demonstrated that reversible continuous noise exposure may induce a temporary threshold shift (TTS) with a permanent degeneration of auditory nerve fibers, although hair cells remain intact. To probe the impact of TTS-inducing impulse noise exposure on hearing, CBA/J Mice were exposed to noise impulses with peak pressures of 145 dB SPL. We found that 30 min after exposure, the noise caused a mean elevation of ABR thresholds of ~30 dB and a reduction in DPOAE amplitude. Four weeks later, ABR thresholds and DPOAE amplitude were back to normal in the higher frequency region (8–32 kHz). At lower frequencies, a small degree of PTS remained. Morphological evaluations revealed a disturbance of the stereociliary bundle of outer hair cells, mainly located in the apical regions. On the other hand, the reduced suprathreshold ABR amplitudes remained until 4 weeks later. A loss of synapse numbers was observed 24 h after exposure, with full recovery two weeks later. Transmission electron microscopy revealed morphological changes at the ribbon synapses by two weeks post exposure. In addition, increased levels of oxidative stress were observed immediately after exposure, and maintained for a further 2 weeks. These results clarify the pathology underlying impulse noise-induced sensory dysfunction, and suggest possible links between impulse-noise injury, cochlear cell morphology, metabolic changes, and hidden hearing loss.

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Hidden hearing loss is associated with loss of ribbon synapses of cochlea inner hair cells

Bioscience Reports ◽

10.1042/bsr20201637 ◽

2021 ◽

Author(s):

Feng Song ◽

Bin Gan ◽

Na Wang ◽

Zhe Wang ◽

An-ting Xu

Keyword(s):

Hearing Loss ◽

Hair Cell ◽

Noise Exposure ◽

Repeated Exposure ◽

Ribbon Synapse ◽

Intensity Noise ◽

Auditory Function ◽

Ribbon Synapses ◽

Brainstem Response ◽

Hidden Hearing Loss

This study aimed to observe the changes in the cochlea ribbon synapses after repeated exposure to moderate-to-high intensity noise. Guinea pigs received 95 dB SPL white noise exposure 4 hours a day for consecutive 7 days (we regarded it a medium-term and moderate-intensity noise, or MTMI noise). Animals were divided into 4 groups: Control, 1DPN (1-day post noise), 1WPN (1-week post noise), and 1MPN (1-month post noise). Auditory function analysis by ABR and CAP recordings, as well as ribbon synapse morphological analyses by immunohistochemistry (Ctbp2 and PSD95 staining) were performed one day, one week, and one month after noise exposure. After MTMI noise exposure, the amplitudes of auditory brainstem response (ABR) I and III waves were suppressed. The compound action potential (CAP) threshold was elevated, and CAP amplitude was reduced in the 1DPN group. No apparent changes in hair cell shape, arrangement or number were observed, but the number of ribbon synapse was reduced. The 1WPN and 1MPN groups showed that part of ABR and CAP changes recovered, as well as the synapse number. The defects in cochlea auditory function and synapse changes were observed mainly in the high-frequency region. Together, repeated exposure in MTMI noise can cause hidden hearing loss, which is partially reversible after leaving the noise environment; and MTMI noise induced hidden hearing loss is associated with inner hair cell ribbon synapses.

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Constant Light Dysregulates Cochlear Circadian Clock and Exacerbates Noise-Induced Hearing Loss

International Journal of Molecular Sciences ◽

10.3390/ijms21207535 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7535

Author(s):

Chao-Hui Yang ◽

Chung-Feng Hwang ◽

Jiin-Haur Chuang ◽

Wei-Shiung Lian ◽

Feng-Sheng Wang ◽

...

Keyword(s):

Hearing Loss ◽

Circadian Clock ◽

Auditory System ◽

High Intensity ◽

Noise Exposure ◽

Clock Genes ◽

Outer Hair Cells ◽

Constant Light ◽

Noise Induced Hearing Loss ◽

Brainstem Response

Noise-induced hearing loss is one of the major causes of acquired sensorineural hearing loss in modern society. While people with excessive exposure to noise are frequently the population with a lifestyle of irregular circadian rhythms, the effects of circadian dysregulation on the auditory system are still little known. Here, we disturbed the circadian clock in the cochlea of male CBA/CaJ mice by constant light (LL) or constant dark. LL significantly repressed circadian rhythmicity of circadian clock genes Per1, Per2, Rev-erbα, Bmal1, and Clock in the cochlea, whereas the auditory brainstem response thresholds were unaffected. After exposure to low-intensity (92 dB) noise, mice under LL condition initially showed similar temporary threshold shifts to mice under normal light–dark cycle, and mice under both conditions returned to normal thresholds after 3 weeks. However, LL augmented high-intensity (106 dB) noise-induced permanent threshold shifts, particularly at 32 kHz. The loss of outer hair cells (OHCs) and the reduction of synaptic ribbons were also higher in mice under LL after noise exposure. Additionally, LL enhanced high-intensity noise-induced 4-hydroxynonenal in the OHCs. Our findings convey new insight into the deleterious effect of an irregular biological clock on the auditory system.

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Cochlear Synaptopathy and Noise-Induced Hidden Hearing Loss

Neural Plasticity ◽

10.1155/2016/6143164 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 23

Author(s):

Lijuan Shi ◽

Ying Chang ◽

Xiaowei Li ◽

Steve Aiken ◽

Lijie Liu ◽

...

Keyword(s):

Hearing Loss ◽

Noise Exposure ◽

Human Subjects ◽

Spiral Ganglion ◽

Nerve Fibers ◽

Type I ◽

Functional Deficits ◽

Ganglion Neurons ◽

Hidden Hearing Loss ◽

Signal Coding

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.

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Effects of Recreational Noise on Threshold and Suprathreshold Measures of Auditory Function

Seminars in Hearing ◽

10.1055/s-0037-1606325 ◽

2017 ◽

Vol 38 (04) ◽

pp. 298-318 ◽

Cited By ~ 35

Author(s):

Colleen Le Prell ◽

Scott Griffiths ◽

Edward Lobarinas ◽

Angela Fulbright

Keyword(s):

Hearing Loss ◽

Noise Exposure ◽

Nerve Fibers ◽

Broadband Noise ◽

Threshold Shift ◽

Distortion Product Otoacoustic Emission ◽

Hearing Tests ◽

Indirect Measure ◽

Brainstem Response ◽

Exposure History

AbstractNoise exposure that causes a temporary threshold shift but no permanent threshold shift can cause degeneration of synaptic ribbons and afferent nerve fibers, with a corresponding reduction in wave I amplitude of the auditory brainstem response (ABR) in animals. This form of underlying damage, hypothesized to also occur in humans, has been termed synaptopathy, and it has been hypothesized that there will be a hidden hearing loss consisting of functional deficits at suprathreshold stimulus levels. This study assessed whether recreational noise exposure history was associated with smaller ABR wave I amplitude and poorer performance on suprathreshold auditory test measures. Noise exposure histories were collected from 26 men and 34 women with hearing thresholds ≤ 25 dB hearing loss (HL; 250 Hz to 8 kHz), and a variety of functional suprathreshold hearing tests were performed. Wave I amplitudes of click-evoked ABR were obtained at 70, 80, 90, and 99 dB (nHL) and tone-burst evoked ABR were obtained at 90 dB nHL. Speech recognition performance was measured in quiet and in competing noise, using the Words in Noise test, and the NU-6 word list in broadband noise (BBN). In addition, temporal summation to tonal stimuli was assessed in quiet and in competing BBN. To control for the effects of subclinical conventional hearing loss, distortion product otoacoustic emission amplitude, an indirect measure of outer hair cell integrity, was measured. There was no statistically significant relationship between noise exposure history scores and ABR wave I amplitude in either men or women for any of the ABR conditions. ABR wave I amplitude and noise exposure history were not reliably correlated with suprathreshold functional hearing tests. Taken together, this study found no evidence of noise-induced decreases in ABR wave I amplitude or signal processing in noise in a cohort of subjects with a history of recreational noise exposure.

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