scholarly journals Applicability of subcortical EEG metrics of synaptopathy to older listeners with impaired audiograms

2018 ◽  
Author(s):  
Markus Garrett ◽  
Sarah Verhulst
Keyword(s):  
Hearing Loss ◽  
High Frequency ◽  
Sound Pressure ◽  
Outer Hair Cell ◽  
Cell Function ◽  
Auditory Brainstem ◽  
Auditory Brainstem Responses ◽  
Individual Factors ◽  
Noise Floor ◽  
Age Related

AbstractEmerging evidence suggests that cochlear synaptopathy is a common feature of sensorineural hearing loss, but it is not known whether electrophysiological metrics targeting synaptopathy in animals can be applied to a broad range of people, such as those with impaired audiograms. This study investigates the applicability of subcortical electrophysiological measures associated with synaptopathy such as auditory brainstem responses (ABRs) and envelope following responses (EFRs) in older participants with high-frequency sloping audiograms. This is important for the development of reliable and sensitive synaptopathy diagnostics in people with normal or impaired outer-hair-cell function. Broadband click-ABRs at different sound pressure levels and EFRs to amplitude-modulated stimuli were recorded, as well as relative EFR and ABR metrics which reduce individual factors such as head size and noise floor level. Most tested metrics showed significant differences between the groups and did not always follow the trends expected from synaptopathy. Audiometric hearing loss and age-related hearing related deficits interacted to affect the electrophysiological metrics and complicated their interpretation in terms of synaptopathy. This study contributes to a better understanding of how electrophysiological synaptopathy metrics differ in ears with healthy and impaired audiograms, which is an important first step towards unravelling the perceptual consequences of synaptopathy.

Auditory Brainstem Responses in a Case of High-Frequency Conductive Hearing Loss

1985 ◽  
Vol 50 (4) ◽  
pp. 346-350 ◽  
Author(s):  
Michael P. Gorga ◽  
Jan K. Reiland ◽  
Kathryn A. Beauchaine
Keyword(s):  
Hearing Loss ◽  
High Frequency ◽  
Conductive Hearing Loss ◽  
Auditory Brainstem ◽  
Intensity Function ◽  
Auditory Brainstem Responses ◽  
Normal Limits ◽  
Interpeak Latency ◽  
Lower Limits ◽  
Conductive Hearing

Click-evoked auditory brainstem responses were measured in a patient with high-frequency conductive hearing loss. As is typical in cases of conductive hearing loss, Wave I latency was prolonged beyond normal limits. Interpeak latency differences were just below the lower limits of the normal range. The Wave V latency-intensity function, however was abnormally steep. This pattern is explained by the hypothesis that the slope of the latency-intensity function is determined principally by the configuration of the hearing loss. In cases of high-frequency hearing loss (regardless of the etiology), the response may be dominated by more apical regions of the cochlea at lower intensities and thus have a longer latency.

scholarly journals Deletion of Oncomodulin Gives Rise to Early Progressive Cochlear Dysfunction in C57 and CBA Mice

2021 ◽  
Vol 13 ◽  
Author(s):  
Leslie K. Climer ◽  
Aubrey J. Hornak ◽  
Kaitlin Murtha ◽  
Yang Yang ◽  
Andrew M. Cox ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cell Function ◽  
Otoacoustic Emission ◽  
Cell Types ◽  
Auditory Brainstem ◽  
Outer Hair Cells ◽  
Distortion Product Otoacoustic Emission ◽  
Distortion Product ◽  
Age Related ◽  
Brainstem Response

Ca2+ signaling is a major contributor to sensory hair cell function in the cochlea. Oncomodulin (OCM) is a Ca2+ binding protein (CaBP) preferentially expressed in outer hair cells (OHCs) of the cochlea and few other specialized cell types. Here, we expand on our previous reports and show that OCM delays hearing loss in mice of two different genetic backgrounds: CBA/CaJ and C57Bl/6J. In both backgrounds, genetic disruption of Ocm leads to early progressive hearing loss as measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). In both strains, loss of Ocm reduced hearing across lifetime (hearing span) by more than 50% relative to wild type (WT). Even though the two WT strains have very different hearing spans, OCM plays a considerable and similar role within their genetic environment to regulate hearing function. The accelerated age-related hearing loss (ARHL) of the Ocm KO illustrates the importance of Ca2+ signaling in maintaining hearing health. Manipulation of OCM and Ca2+ signaling may reveal important clues to the systems of function/dysfunction that lead to ARHL.

scholarly journals Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258158
Author(s):  
Neil J. Ingham ◽  
Navid Banafshe ◽  
Clarisse Panganiban ◽  
Julia L. Crunden ◽  
Jing Chen ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Cell Function ◽  
Low Frequency ◽  
Mutant Mice ◽  
Auditory Brainstem Responses ◽  
Distortion Product Otoacoustic Emission ◽  
Inner Hair Cell ◽  
Distortion Product ◽  
Age Related

Age-related hearing loss in humans (presbycusis) typically involves impairment of high frequency sensitivity before becoming progressively more severe at lower frequencies. Pathologies initially affecting lower frequency regions of hearing are less common. Here we describe a progressive, predominantly low-frequency recessive hearing impairment in two mutant mouse lines carrying different mutant alleles of the Klhl18 gene: a spontaneous missense mutation (Klhl18lowf) and a targeted mutation (Klhl18tm1a(KOMP)Wtsi). Both males and females were studied, and the two mutant lines showed similar phenotypes. Threshold for auditory brainstem responses (ABR; a measure of auditory nerve and brainstem neural activity) were normal at 3 weeks old but showed progressive increases from 4 weeks onwards. In contrast, distortion product otoacoustic emission (DPOAE) sensitivity and amplitudes (a reflection of cochlear outer hair cell function) remained normal in mutants. Electrophysiological recordings from the round window of Klhl18lowf mutants at 6 weeks old revealed 1) raised compound action potential thresholds that were similar to ABR thresholds, 2) cochlear microphonic potentials that were normal compared with wildtype and heterozygous control mice and 3) summating potentials that were reduced in amplitude compared to control mice. Scanning electron microscopy showed that Klhl18lowf mutant mice had abnormally tapering of the tips of inner hair cell stereocilia in the apical half of the cochlea while their synapses appeared normal. These results suggest that Klhl18 is necessary to maintain inner hair cell stereocilia and normal inner hair cell function at low frequencies.

scholarly journals Evaluation of the Effects of Chronic Injection of D-Galactose on Auditory Brainstem Responses as a Model for Studying Age-Related Hearing Loss

2019 ◽  
Author(s):  
Elham Tavanai ◽  
Ghassem Mohammadkhani
Keyword(s):  
Hearing Loss ◽  
Wistar Rats ◽  
Natural Aging ◽  
Tone Burst ◽  
Auditory Brainstem ◽  
Young Group ◽  
Auditory Brainstem Responses ◽  
Age Related ◽  
Significant Difference ◽  
Age Related Hearing Loss

The D-galactose induced mimetic aging rat model has been widely used in studies of age-associated diseases recently. Evidence indicates that D-GAL could also play a key role in age-related hearing loss. However, there is conflicting data about the relationship between the D-GAL injection and tone-burst auditory brainstem responses (ABRs). The present study aimed to compare ABRs in D-GAL injected rats compared with young and naturally aged rats. Tone-burst ABR was recorded and analyzed at the frequencies of 4,6,8,12 and 16 kHz in male young (3-month-old, n=10), naturally aging (18-month-old, n=10) and D-GAL injected (3-month-old, 500 mg/kg D-GAL injection for 8 weeks, n=10) Wistar rats. When the ABRs thresholds obtained in the D-GAL group and the natural aging group were compared with the thresholds in the young group, we observed a significant increase in thresholds, which affected all of the frequencies (P<0.05). A statistically significant decrease in amplitude of wave PI at 4 and 8 kHz, PII at 4,8 kHz, PIV at 4,6,8,12 and 16 kHz was also observed in naturally aging group compared with young group. However, in D-GAL group, a significant difference was exclusively detected in amplitude of PIII at 4 kHz. Latency did not reveal any significant difference between the groups (P>0.05). The present study confirmed that experimental injection of 500 mg/kg/day D-GAL for 8 weeks to Wistar rats could lead to ABRs threshold shifts but not latency. Because there are several types of presbycusis, further studies are needed to determine what type of presbycusis is induced by D-GAL and where is the first region affected by it to provide the best treatment and prevention methods. © 2019 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2019;57(5):281-288.

scholarly journals Oncomodulin Delays Age-Related Hearing Loss in C57 and CBA Mice

2021 ◽  
Author(s):  
Leslie K Climer ◽  
Aubrey J Hornak ◽  
Kaitlin Murtha ◽  
Yang Yang ◽  
Andrew M Cox ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cell Function ◽  
Otoacoustic Emission ◽  
Auditory Brainstem ◽  
Outer Hair Cells ◽  
Distortion Product Otoacoustic Emission ◽  
Progressive Hearing Loss ◽  
Distortion Product ◽  
Age Related ◽  
Brainstem Response

Ca2+ signaling is a major contributor to sensory hair cell function in the cochlea. Oncomodulin (OCM) is a Ca2+ binding protein preferentially expressed in outer hair cells of the cochlea and few other specialized cell types. Here, we expand on our previous reports and show that OCM prevents early progressive hearing loss in mice of two different genetic backgrounds: CBA/CaJ and C57Bl/6J. In both backgrounds, genetic disruption of Ocm leads to early progressive hearing loss as measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). In both strains, loss of Ocm reduced hearing across lifetime (hearing span) by more than 50% relative to wild type (WT). Even though the two WT strains have very different hearing spans, OCM plays a considerable and similar role within their genetic environment to regulate hearing function. The accelerated ARHL of the Ocm KO illustrates the importance of Ca2+ signaling in maintaining hearing health.

scholarly journals Folic acid as preventive therapy for hearing loss: effect of ototoxic drug consumption

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Carmen Morais-Moreno ◽  
María del Pilar Garzón-Riveros ◽  
Silvia Murillo-Cuesta ◽  
Lourdes Rodríguez-de la Rosa ◽  
Ana Montero ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Folic Acid ◽  
Stria Vascularis ◽  
Auditory Brainstem ◽  
Auditory Brainstem Responses ◽  
Control Group ◽  
Spiral Ligament ◽  
Folate Supplementation ◽  
Age Related ◽  
Ototoxic Drugs

AbstractIntroductionAge-related hearing loss (ARHL) is a sensory impairment, with a dramatic increase in its incidence, which is caused by genetic and environmental factors such as noise and ototoxic drugs. Recent studies correlated ARHL to elevated plasma homocysteine (Hcy) by folate deficiency, suggesting that reduction of Hcy levels by folate supplementation could potentially ameliorate ARHL.Hyperhomocysteinemia (HHcy), a status that contributes to ARHL, may also arise from malfunction of Hcy remethylation by betaine homocysteine S-methyltransferases (BHMTs) and methionine synthase in the methionine cycle. The expression and/or activity of these enzymes may be altered by ototoxic drugs, including paracetamol (APAP).ObjectiveTo determine the effect of APAP in cochlear morphology and function of control and Bhmt-/- mice, and to analyze putative preventive effects of folic acid (FA) supplementation.Materials and MethodsTwo-month-old Bhmt-/- mice (n = 47), with greater dependence on folate metabolism for Hcy remethylation, and Bhmt + / + mice (n = 42) were fed control or FA supplemented diets for 30 days. The last day APAP (250 mg/kg) or placebo were injected intraperitoneally.Hearing was evaluated by recording auditory brainstem responses (ABR) at the beginning of the experiment and after treatments. Picrosirius red staining was used for evaluation of the cochlear lateral wall cytoarchitecture. Plasma and hepatic metabolite levels were determined by HPLC or on Spinlab 100® autoanalyzer.ResultsLoss of Bhmt expression induced HHcy, but an impact on hearing acuity was not observed. Acute APAP administration did not induce ABR threshold shifts. However, following ototoxic treatment, changes of 5–17% in the areas of the stria vascularis and spiral ligament were detected between Bhmt-/- mice under different dietary treatments; cochlear structures of Bhmt-/- mice receiving APAP plus FA supplementation resemble those of the control group. APAP increases susceptibility to ototoxic damage in the presence of HHcy.DiscussionBHMT plays a central role in cochlear methionine metabolism. FA supplementation modulates Hcy levels, contributing to a proper remethylation status that prevents ARHL.

scholarly journals Istradefylline Mitigates Age-Related Hearing Loss in C57BL/6J Mice

2021 ◽  
Vol 22 (15) ◽  
pp. 8000
Author(s):  
Min Shin ◽  
Madhavi Pandya ◽  
Kristan Espinosa ◽  
Ravindra Telang ◽  
Jordi Boix ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cognitive Function ◽  
Hearing Aids ◽  
Treatment Strategies ◽  
Auditory Brainstem ◽  
Auditory Brainstem Responses ◽  
Dependent Manner ◽  
Object Recognition Test ◽  
Age Related ◽  
Age Related Hearing Loss

Age-related hearing loss (ARHL) is the most common sensory disorder among older people, and yet, the treatment options are limited to medical devices such as hearing aids and cochlear implants. The high prevalence of ARHL mandates the development of treatment strategies that can prevent or rescue age-related cochlear degeneration. In this study, we investigated a novel pharmacological strategy based on inhibition of the adenosine A2A receptor (A2AR) in middle aged C57BL/6 mice prone to early onset ARHL. C57BL/6J mice were treated with weekly istradefylline (A2AR antagonist; 1 mg/kg) injections from 6 to 12 months of age. Auditory function was assessed using auditory brainstem responses (ABR) to tone pips (4–32 kHz). ABR thresholds and suprathreshold responses (wave I amplitudes and latencies) were evaluated at 6, 9, and 12 months of age. Functional outcomes were correlated with quantitative histological assessments of sensory hair cells. Cognitive function was assessed using the Morris water maze and the novel object recognition test, and the zero maze test was used to assess anxiety-like behaviour. Weekly injections of istradefylline attenuated ABR threshold shifts by approximately 20 dB at mid to high frequencies (16–32 kHz) but did not improve ABR suprathreshold responses. Istradefylline treatment improved hair cell survival in a turn-dependent manner, whilst the cognitive function was unaffected by istradefylline treatment. This study presents the first evidence for the rescue potential of istradefylline in ARHL and highlights the role of A2AR in development of age-related cochlear degeneration.

Effect of Tinnitus on Distortion Product Otoacoustic Emissions Varies With Hearing Loss

2013 ◽  
Vol 22 (1) ◽  
pp. 125-134 ◽  
Author(s):  
Fatima T. Husain
Keyword(s):  
Hearing Loss ◽  
High Frequency ◽  
Otoacoustic Emissions ◽  
Outer Hair Cell ◽  
Cell Function ◽  
Normal Hearing ◽  
Neural Mechanisms ◽  
Distortion Product Otoacoustic Emissions ◽  
Distortion Product ◽  
Main Effect

Purpose The aim of this study was to measure the effect of tinnitus, while accounting for the effect of hearing loss and aging, on distortion product otoacoustic emissions (DPOAEs). Method DPOAEs were measured twice in both ears in 5 groups of participants: young adults with normal hearing, middle-age adults with normal hearing, adults with high-frequency sensorineural hearing loss, age-matched adults with similar hearing loss and tinnitus, and adults with normal hearing and chronic tinnitus. Results Multivariate analysis revealed a main effect of hearing loss and age, but no effect of tinnitus, across all 5 groups. Separate tests revealed significant effects of age and tinnitus in the normal-hearing groups and hearing loss in adults with or without tinnitus, but no effect of tinnitus in those with hearing loss. Conclusion DPOAE levels in the group of adults with hearing loss and tinnitus were diminished, but those in the group with normal hearing and tinnitus were enhanced, relative to DPOAE levels in the controls. Outer hair cell function, as indexed by DPOAEs, exhibits a complex association with tinnitus, and this has implications in the use of DPOAEs as a tool both for testing for tinnitus presence and for creating a model of neural mechanisms underlying tinnitus.

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