The Derived-Band Envelope Following Response and its Sensitivity to Sensorineural Hearing Deficits

AbstractThe envelope following response (EFR) has been proposed as a non-invasive marker of synaptopathy in animal models. However, its amplitude is affected by the spread of basilar-membrane excitation and other coexisting sensorineural hearing deficits. This study aims to (i) improve frequency specificity of the EFR by introducing a derived-band EFR (DBEFR) technique and (ii) investigate the effect of lifetime noise exposure, age and outer-hair-cell (OHC) damage on DBEFR magnitudes. Additionally, we adopt a modelling approach to validate the frequency-specificity of the DBEFR and test how different aspects of sensorineural hearing loss affect peripheral generators. The combined analysis of simulations and experimental data proposes that the DBEFRs extracted from the [2-6]-kHz frequency band is a sensitive and frequency-specific measure of synaptopathy in humans. Individual variability in DBEFR magnitudes among listeners with normal audiograms was explained by their self-reported amount of experienced lifetime noise-exposure and corresponded to amplitude variability predicted by synaptopathy. Older listeners consistently had reduced DBEFR magnitudes in comparison to young normal-hearing listeners, in correspondence to how age-induced synaptopathy affects EFRs and compromises temporal envelope encoding. Lastly, OHC damage was also seen to affect the DBEFR magnitude, hence this marker should be combined with a sensitive marker of OHC-damage to offer a differential diagnosis of synaptopathy in listeners with impaired audiograms.

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Towards a differential diagnosis of cochlear synaptopathy and outer-hair-cell deficits in mixed sensorineural hearing loss pathologies

10.1101/19008680 ◽

2019 ◽

Cited By ~ 6

Author(s):

Viacheslav Vasilkov ◽

Sarah Verhulst

Keyword(s):

Hearing Loss ◽

Differential Diagnosis ◽

Hair Cell ◽

Sensorineural Hearing Loss ◽

Noise Exposure ◽

Outer Hair Cell ◽

Cell Damage ◽

Sensorineural Hearing ◽

Inner Hair Cell ◽

Hearing Thresholds

AbstractDamage to the auditory periphery is more widespread than predicted by the gold-standard clinical audiogram. Noise exposure, ototoxicity and aging can destroy cochlear inner-hair-cell afferent synapses and result in a degraded subcortical representation of sound while leaving hearing thresholds unaffected. Damaged afferent synapses, i.e. cochlear synaptopathy, can be quantified using histology, but a differential diagnosis in living humans is difficult: histology cannot be applied and existing auditory evoked potential (AEP) metrics for synaptopathy become insensitive when other sensorineural hearing impairments co-exist (e.g., outer-hair-cell damage associated with elevated hearing thresholds). To develop a non-invasive diagnostic method which quantifies synaptopathy in humans and animals with normal or elevated hearing thresholds, we employ a computational model approach in combination with human AEP and psychoacoustics. We propose the use of a sensorineural hearing loss (SNHL) map which comprises two relative AEP-based metrics to quantify the respective degrees of synaptopathy and OHC damage and evaluate to which degree our predictions of AEP alterations can explain individual data-points in recorded SNHL maps from male and female listeners with normal or elevated audiometric thresholds. We conclude that SNHL maps can offer a more precise diagnostic tool than existing AEP methods for individual assessment of the synaptopathy and OHC-damage aspect of sensorineural hearing loss.Significance StatementHearing loss ranks fourth in global causes for disability and risk factors include noise exposure, ototoxicity and aging. The most vulnerable parts of the cochlea are the inner-hair-cell afferent synapses and their damage (cochlear synaptopathy) results in a degraded subcortical representation of sound. While synaptopathy can be estimated reliably using histology, it cannot be quantified this way in living humans. Secondly, other co-existing sensorineural hearing deficits (e.g., outer-hair-cell damage) can complicate a differential diagnosis. To quantify synaptopathy in humans and animals with normal or elevated hearing thresholds, we adopt a theoretical and interdisciplinary approach. Sensitive diagnostic metrics for synaptopathy are crucial to assess its prevalence in humans, study its impact on sound perception and yield effective hearing restoration strategies.

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The role of microRNAs in gliomas – Therapeutic implications

Current Molecular Pharmacology ◽

10.2174/1874467213666200730115837 ◽

2020 ◽

Vol 13 ◽

Author(s):

Theodora Katsila ◽

Dimitrios Kardamakis

Keyword(s):

Complex Disease ◽

Malignant Gliomas ◽

Kappa Statistic ◽

Individual Variability ◽

Response To Treatment ◽

Disease Phenotype ◽

Therapeutic Implications ◽

Non Invasive ◽

Gene Environment ◽

Sas Macro

Background: Malignant gliomas constitute a complex disease phenotype that demands optimum decisionmaking. Despite being the most common type of primary brain tumors, gliomas are highly heterogeneous when their pathophysiology and response to treatment are considered. Such inter-individual variability also renders differential and early diagnosis extremely difficult. Recent evidence highlight that the gene-environment interplay becomes of fundamental importance in oncogenesis and progression of gliomas. Objective: To unmask key features of the gliomas disease phenotype and map the inter-individual variability of patients, we explore genotype-to-phenotype associations. Emphasis is put on microRNAs as they regulate gene expression, have been implicated in the pathogenesis of gliomas and may serve as theranostics, empowering non-invasive strategies (circulating free or in exosomes). Method: We mined text and omic datasets (as of 2019) and conducted a mixed-method content analysis. A novel framework was developed to meet the aims of our analysis, interrogating data in terms of content and context. We relied on literature data from PubMed/Medline and Scopus, as they are considered the largest abstract and citation databases of peer-reviewed literature. To avoid selection biases, both publicly available and private texts have been assessed. Both percent agreement and Cohen's kappa statistic have been calculated to avoid biases by SAS macro MAGREE with multicategorical ratings. Results: Gliomas serve as a paradigm for multifaceted datasets, despite data sparsity and scarcity. miRNAs and miRNAbased therapeutics are ready for prime time. Exosomal miRNAs empower non-invasive strategies, surpassing circulating free miRNAs, when accuracy and precision are considered. Conclusion: miRNAs holds promise as theranostics.

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Sensorineural Hearing Loss Due to Exposure of Noisy Trains on Populations Around Turirejo Train Railroad Cross

JURNAL KESEHATAN LINGKUNGAN ◽

10.20473/jkl.v12i1.2020.59-68 ◽

2020 ◽

Vol 12 (1) ◽

pp. 59

Author(s):

Diana Kusuma Wardhani ◽

Jojok Mukono Mukono

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Hair Cells ◽

Noise Intensity ◽

Noise Exposure ◽

Sound Level ◽

Sensorineural Hearing ◽

High Noise ◽

Railroad Tracks ◽

The Government

Introduction: As one of the preferred modes of land transportation, the frequency of train services was very high. One of the negative impacts arising from train activity was noise. The high noise intensity of the train causes hearing loss. Method: This study aims to analyze the differences in the incidence of hearing loss in 2 groups of residents in Turirejo Lawang Malang. This research used the observational method and the data were analyzed descriptive qualitative. A total of 20 people were selected as respondents by purposive sampling. Noise intensity was measured by Sound Level Meter and audiometric measurements were examined at SIMA Malang Laboratory. Result and Discussion: The prevalence of sensorineural hearing loss was more common in residents whose homes at 3-7 m away from the railroad tracks. In addition, residents who lived at least 15 years at a distance of 3-7 m also experienced more hearing loss. One cause of hearing loss is due to exposure to high noise and for a long time and will damage the hair cells in the cochlea, causing hearing loss. If noise exposure continues and for a long period of time damage to hair cells will be permanent and cannot return to normal. Conclusion: There needs to be a policy from the government in determining the minimum limit of the distance of the house to the railroad tracks. In addition, it is necessary to install a barrier near people’s homes to reduce noise.

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Low-Frequency Noise Exposure Induces Extensive Hearing Loss by Reverse Traveling of Basilar Membrane From Cochlear Apex to Basal Turn?

SSRN Electronic Journal ◽

10.2139/ssrn.3954087 ◽

2021 ◽

Author(s):

Junping Liu ◽

Changming Liu ◽

Miaoan Chen ◽

Pin Dong ◽

Richard Fahlman ◽

...

Keyword(s):

Hearing Loss ◽

Noise Exposure ◽

Basilar Membrane ◽

Low Frequency ◽

Frequency Noise ◽

Low Frequency Noise ◽

Basal Turn

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Joint Modelling Of Individual Trajectories, Within-Individual Variability And A Later Outcome: Systolic Blood Pressure Through Childhood And Left Ventricular Mass In Early Adulthood

American Journal of Epidemiology ◽

10.1093/aje/kwaa224 ◽

2020 ◽

Author(s):

Richard M A Parker ◽

George Leckie ◽

Harvey Goldstein ◽

Laura D Howe ◽

Jon Heron ◽

...

Keyword(s):

Blood Pressure ◽

Left Ventricular Mass ◽

Random Effect ◽

Early Adulthood ◽

Credible Interval ◽

Left Ventricular ◽

Individual Variability ◽

Joint Modelling ◽

Ventricular Mass ◽

Modelling Approach

Abstract Within-individual variability of repeatedly-measured exposures may predict later outcomes: e.g. blood pressure (BP) variability (BPV) is an independent cardiovascular risk factor above and beyond mean BP. Since two-stage methods, known to introduce bias, are typically used to investigate such associations, we introduce a joint modelling approach, examining associations of mean BP and BPV across childhood to left ventricular mass (indexed to height; LVMI) in early adulthood with data (collected 1990-2011) from the UK’s Avon Longitudinal Study of Parents and Children cohort. Using multilevel models, we allow BPV to vary between individuals (a “random effect”) as well as to depend on covariates (allowing for heteroscedasticity). We further distinguish within-clinic variability (“measurement error”) from visit-to-visit BPV. BPV was predicted to be greater at older ages, at higher bodyweights, and in females, and was positively correlated with mean BP. BPV had a weak positive association with LVMI (10% increase in within-individual BP variance was predicted to increase LVMI by 0.21% (95% credible interval: -0.23%, 0.69%)), but this association became negative (-0.78%, 95% credible interval: -2.54%, 0.22%)) once the effect of mean BP on LVMI was adjusted for. This joint modelling approach offers a flexible method of relating repeatedly-measured exposures to later outcomes.

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Effects of coiling on the micromechanics of the mammalian cochlea

Journal of The Royal Society Interface ◽

10.1098/rsif.2005.0049 ◽

2005 ◽

Vol 2 (4) ◽

pp. 341-348 ◽

Cited By ~ 32

Author(s):

Hongxue Cai ◽

Daphne Manoussaki ◽

Richard Chadwick

Keyword(s):

Outer Hair Cell ◽

Basilar Membrane ◽

Travelling Waves ◽

Organ Of Corti ◽

Tectorial Membrane ◽

Governing Equations ◽

Element Analysis ◽

Curvature Effects ◽

Curvilinear Coordinate ◽

Cochlear Partition

The cochlea transduces sound-induced vibrations in the inner ear into electrical signals in the auditory nerve via complex fluid–structure interactions. The mammalian cochlea is a spiral-shaped organ, which is often uncoiled for cochlear modelling. In those few studies where coiling has been considered, the cochlear partition was often reduced to the basilar membrane only. Here, we extend our recently developed hybrid analytical/numerical micromechanics model to include curvature effects, which were previously ignored. We also use a realistic cross-section geometry, including the tectorial membrane and cellular structures of the organ of Corti, to model the apical and basal regions of a guinea-pig cochlea. We formulate the governing equations of the fluid and solid domains in a curvilinear coordinate system. The WKB perturbation method is used to treat the propagation of travelling waves along the coiled cochlear duct, and the O (1) system of the governing equations is solved in the transverse plane using finite-element analysis. We find that the curvature of the cochlear geometry has an important functional significance; at the apex, it greatly increases the shear gain of the cochlear partition, which is a measure of the bending efficiency of the outer hair cell stereocilia.

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Childhood sensorineural hearing loss: effects of combined exposure with aging or noise exposure later in life

European Archives of Oto-Rhino-Laryngology ◽

10.1007/s00405-015-3649-y ◽

2015 ◽

Vol 273 (5) ◽

pp. 1099-1105 ◽

Cited By ~ 5

Author(s):

Lisa Aarhus ◽

Kristian Tambs ◽

Per Nafstad ◽

Eskil Bjørgan ◽

Bo Engdahl

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Noise Exposure ◽

Sensorineural Hearing ◽

Combined Exposure

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Analysis of Click and Swept-Tone Auditory Brainstem Response Results for Moderate and Severe Sensorineural Hearing Loss

Audiology and Neurotology ◽

10.1159/000507691 ◽

2020 ◽

Vol 25 (6) ◽

pp. 336-344

Author(s):

Jingqian Tan ◽

Jia Luo ◽

Xin Wang ◽

Yanbing Jiang ◽

Xiangli Zeng ◽

...

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Auditory Brainstem Response ◽

Basilar Membrane ◽

Auditory Brainstem ◽

Sensorineural Hearing ◽

Control Group ◽

Hearing Sensitivity ◽

Brainstem Response ◽

Frequency Components

Introduction: Auditory brainstem response (ABR) is one of the commonly used methods in clinical settings to evaluate the hearing sensitivity and auditory function. The current ABR measurement usually adopts click sound as the stimuli. However, there may be partial ABR amplitude attenuation due to the delay characteristics of the cochlear traveling wave along the basilar membrane. To solve that problem, a swept-tone method was proposed, in which the show-up time of different frequency components was adjusted to compensate the delay characteristics of the cochlear basilar membrane; therefore, different ABR subcomponents of different frequencies were synchronized. Methods: The normal hearing group, moderate sensorineural hearing loss group, and severe sensorineural hearing loss group underwent click ABR and swept-tone ABR with different stimulus intensities. The latencies and amplitudes of waves I, III, and V in 2 detections were recorded. Results: It was found that the latency of each of the recorded I, III, and V waves detected by swept-tone ABR was shorter than that by click ABR in both the control group and experimental groups. In addition, the amplitude of each of the recorded I, III, and V waves, except V waves under 60 dB nHL in the moderate sensorineural hearing loss group, detected by swept-tone ABR was larger than that by click ABR. The results also showed that the swept-tone ABR could measure the visible V waves at lower stimulus levels in the severe sensorineural hearing loss group. Conclusion: Swept-tone improves the ABR waveforms and helps to obtain more accurate threshold to some extent. Therefore, the proposed swept-tone ABR may provide a new solution for better morphology of ABR waveform, which can help to make more accurate diagnosis about the hearing functionality in the clinic.

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Spontaneous otoacoustic emission recordings during contralateral pure-tone activation of medial olivocochlear reflex

Physiology International ◽

10.1556/2060.104.2017.2.7 ◽

2017 ◽

Vol 104 (2) ◽

pp. 171-182

Author(s):

E Bulut ◽

L Öztürk

Keyword(s):

Pure Tone ◽

Outer Hair Cell ◽

Basilar Membrane ◽

Otoacoustic Emission ◽

Frequency Discrimination ◽

Frequency Range ◽

Unilateral Deafness ◽

Transient Evoked Otoacoustic Emission ◽

Medial Olivocochlear ◽

Bilateral Deafness

We hypothesized that cochlear frequency discrimination occurs through medial olivocochlear efferent (MOCE)-induced alterations in outer hair cell (OHC) electromotility, which is independent from basilar membrane traveling waves. After obtaining informed consent, volunteers with normal hearing (n = 10; mean age: 20.6 ± 1.2 years) and patients with unilateral deafness (n = 10; mean age: 30.2 ± 17.9 years) or bilateral deafness (n = 8; mean age: 30.7 ± 13.8 years) underwent a complete physical and audiological examination, and audiological tests including transient evoked otoacoustic emission and spontaneous otoacoustic emission (TEOAE and SOAE, respectively). SOAE recordings were performed during contralateral pure-tone stimuli at 1 and 3 kHz. SOAE recordings in the presence of contralateral pure-tone stimuli showed frequency-specific activation out of the initial frequency range of SOAE responses. Basilar membrane motion during pure-tone stimulation results from OHC activation by means of MOCE neurons rather than from a traveling wave. Eventually, frequency-specific responses obtained from SOAEs suggested that OHC electromotility may be responsible for frequency discrimination of the cochlea independently from basilar membrane motion.

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