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International Journal of Molecular... Feb 2024In mammalian hearing, type-I afferent auditory nerve fibers comprise the basis of the afferent auditory pathway. They are connected to inner hair cells of the cochlea...
In mammalian hearing, type-I afferent auditory nerve fibers comprise the basis of the afferent auditory pathway. They are connected to inner hair cells of the cochlea via specialized ribbon synapses. Auditory nerve fibers of different physiological types differ subtly in their synaptic location and morphology. Low-spontaneous-rate auditory nerve fibers typically connect on the modiolar side of the inner hair cell, while high-spontaneous-rate fibers are typically found on the pillar side. In aging and noise-damaged ears, this fine-tuned balance between auditory nerve fiber populations can be disrupted and the functional consequences are currently unclear. Here, using immunofluorescent labeling of presynaptic ribbons and postsynaptic glutamate receptor patches, we investigated changes in synaptic morphology at three different tonotopic locations along the cochlea of aging gerbils compared to those of young adults. Quiet-aged gerbils showed about 20% loss of afferent ribbon synapses. While the loss was random at apical, low-frequency cochlear locations, at the basal, high-frequency location it almost exclusively affected the modiolar-located synapses. The subtle differences in volumes of pre- and postsynaptic elements located on the inner hair cell's modiolar versus pillar side were unaffected by age. This is consistent with known physiology and suggests a predominant, age-related loss in the low-spontaneous-rate auditory nerve population in the cochlear base, but not the apex.
Topics: Animals; Gerbillinae; Cochlea; Synapses; Cochlear Nerve; Hair Cells, Auditory, Inner
PubMed: 38473985
DOI: 10.3390/ijms25052738 -
Frontiers in Neuroscience 2023A cochlear implant (CI) is a neurotechnological device that restores total sensorineural hearing loss. It contains a sophisticated speech processor that analyzes and...
A cochlear implant (CI) is a neurotechnological device that restores total sensorineural hearing loss. It contains a sophisticated speech processor that analyzes and transforms the acoustic input. It distributes its time-enveloped spectral content to the auditory nerve as electrical pulsed stimulation trains of selected frequency channels on a multi-contact electrode that is surgically inserted in the cochlear duct. This remarkable brain interface enables the deaf to regain hearing and understand speech. However, tuning of the large (>50) number of parameters of the speech processor, so-called "device fitting," is a tedious and complex process, which is mainly carried out in the clinic through 'one-size-fits-all' procedures. Current fitting typically relies on limited and often subjective data that must be collected in limited time. Despite the success of the CI as a hearing-restoration device, variability in speech-recognition scores among users is still very large, and mostly unexplained. The major factors that underly this variability incorporate three levels: (i) variability in auditory-system of CI-users, (ii) variability in the of electrode-to-auditory nerve (EL-AN) activation, and (iii) lack of objective measures to optimize the fitting. We argue that variability in speech recognition can only be alleviated by using objective patient-specific data for an individualized fitting procedure, which incorporates knowledge from all three levels. In this paper, we propose a series of experiments, aimed at collecting a large amount of objective (i.e., quantitative, reproducible, and reliable) data that characterize the three processing levels of the user's auditory system. Machine-learning algorithms that process these data will eventually enable the clinician to derive reliable and personalized characteristics of the user's auditory system, the quality of EL-AN signal transfer, and predictions of the perceptual effects of changes in the current fitting.
PubMed: 37521701
DOI: 10.3389/fnins.2023.1183126 -
Diversity matters - extending sound intensity coding by inner hair cells via heterogeneous synapses.The EMBO Journal Dec 2023Our sense of hearing enables the processing of stimuli that differ in sound pressure by more than six orders of magnitude. How to process a wide range of stimulus... (Review)
Review
Our sense of hearing enables the processing of stimuli that differ in sound pressure by more than six orders of magnitude. How to process a wide range of stimulus intensities with temporal precision is an enigmatic phenomenon of the auditory system. Downstream of dynamic range compression by active cochlear micromechanics, the inner hair cells (IHCs) cover the full intensity range of sound input. Yet, the firing rate in each of their postsynaptic spiral ganglion neurons (SGNs) encodes only a fraction of it. As a population, spiral ganglion neurons with their respective individual coding fractions cover the entire audible range. How such "dynamic range fractionation" arises is a topic of current research and the focus of this review. Here, we discuss mechanisms for generating the diverse functional properties of SGNs and formulate testable hypotheses. We postulate that an interplay of synaptic heterogeneity, molecularly distinct subtypes of SGNs, and efferent modulation serves the neural decomposition of sound information and thus contributes to a population code for sound intensity.
Topics: Hair Cells, Auditory, Inner; Cochlea; Sound; Synapses; Spiral Ganglion
PubMed: 37800695
DOI: 10.15252/embj.2023114587 -
Scientific Reports Nov 2023Tinnitus, reduced sound-level tolerance, and difficulties hearing in noisy environments are the most common complaints associated with sensorineural hearing loss in...
Tinnitus, reduced sound-level tolerance, and difficulties hearing in noisy environments are the most common complaints associated with sensorineural hearing loss in adult populations. This study aims to clarify if cochlear neural degeneration estimated in a large pool of participants with normal audiograms is associated with self-report of tinnitus using a test battery probing the different stages of the auditory processing from hair cell responses to the auditory reflexes of the brainstem. Self-report of chronic tinnitus was significantly associated with (1) reduced cochlear nerve responses, (2) weaker middle-ear muscle reflexes, (3) stronger medial olivocochlear efferent reflexes and (4) hyperactivity in the central auditory pathways. These results support the model of tinnitus generation whereby decreased neural activity from a damaged cochlea can elicit hyperactivity from decreased inhibition in the central nervous system.
Topics: Adult; Humans; Tinnitus; Auditory Threshold; Hearing; Cochlea; Auditory Perception; Vestibulocochlear Nerve Diseases
PubMed: 38036538
DOI: 10.1038/s41598-023-46741-5 -
European Archives of... Oct 2023Due to the specificity of cochlear implantation (CI) programming parameters and outcomes in cochlear nerve deficiency (CND) patients, this study aimed to investigate the...
PURPOSE
Due to the specificity of cochlear implantation (CI) programming parameters and outcomes in cochlear nerve deficiency (CND) patients, this study aimed to investigate the correlation between programming parameters and outcomes and further compare the difference between normal and CND groups.
METHODS
Ninety (95 ears) CND patients (normal cochlea, 39; malformed cochlea, 56) and seventy-nine (81 ears) normal cochlea patients who underwent CI surgery with either Med-El or Cochlear devices were included. The programming parameters and outcomes evaluated by the questionnaires were collected and compared among the normal CND, malformed CND, and normal groups in the two device groups, and their correlation was analyzed.
RESULTS
In the CND group, a reduced stimulation rate, higher pulse width, and triphasic pulse were needed in some cases. The stimulus levels of the CND group were significantly higher than that of the normal group (p < 0.05), but the outcomes of the CND group were significantly worse than that of the normal group (p < 0.05), and the stimulus level was significantly correlated with the outcomes (p < 0.05). However, there was no difference between normal and malformed CND groups. The non-auditory response was observed in the CND group, especially the ones with malformations.
CONCLUSION
The CI programming parameters of some CND patients need to be adjusted, and a slower stimulation rate and higher pulse width are required sometimes. CND patients need a higher stimulus level than normal patients but their outcomes are poorer. Non-auditory response should be noticed in CND patients during programming.
Topics: Humans; Cochlear Implantation; Cochlear Implants; Cochlear Nerve; Retrospective Studies; Cochlea
PubMed: 37036510
DOI: 10.1007/s00405-023-07949-3 -
The Journal of Pediatrics Nov 2023To evaluate factors influencing the diagnostic yield of comprehensive gene panel testing (CGPT) for hearing loss (HL) in children and to understand the characteristics...
OBJECTIVE
To evaluate factors influencing the diagnostic yield of comprehensive gene panel testing (CGPT) for hearing loss (HL) in children and to understand the characteristics of undiagnosed probands.
STUDY DESIGN
This was a retrospective cohort study of 474 probands with childhood-onset HL who underwent CGPT between 2016 and 2020 at a single center. Main outcomes and measures included the association between clinical variables and diagnostic yield and the genetic and clinical characteristics of undiagnosed probands.
RESULTS
The overall diagnostic yield was 44% (209/474) with causative variants involving 41 genes. While the diagnostic yield was high in the probands with congenital, bilateral, and severe HL, it was low in those with unilateral, noncongenital, or mild HL; cochlear nerve deficiency; preterm birth; neonatal intensive care unit admittance; certain ancestry; and developmental delay. Follow-up studies on 49 probands with initially inconclusive CGPT results changed the diagnostic status to likely positive or negative outcomes in 39 of them (80%). Reflex to exome sequencing on 128 undiagnosed probands by CGPT revealed diagnostic findings in 8 individuals, 5 of whom had developmental delays. The remaining 255 probands were undiagnosed, with 173 (173/255) having only a single variant in the gene(s) associated with autosomal recessive HL and 28% (48/173) having a matched phenotype.
CONCLUSION
CGPT efficiently identifies the genetic etiologies of HL in children. CGPT-undiagnosed probands may benefit from follow-up studies or expanded testing.
Topics: Female; Humans; Child; Infant, Newborn; Retrospective Studies; Premature Birth; Hearing Loss; Deafness; Phenotype; Hearing Loss, Sensorineural; Genetic Testing
PubMed: 37473993
DOI: 10.1016/j.jpeds.2023.113620 -
International Journal of Clinical and... 2023Age-related hearing loss (ARHL) is a progressive sensorineural hearing loss caused by age. The pathogenesis of ARHL is not completely clear at present, but it is closely... (Review)
Review
Age-related hearing loss (ARHL) is a progressive sensorineural hearing loss caused by age. The pathogenesis of ARHL is not completely clear at present, but it is closely related to auditory nerve degeneration, metabolic disorders, vitamin deficiency, and genetics, especially mitochondrial DNA damage. With the acceleration of industrialization and urbanization in our country, the impact of environmental noise is increasing, and ARHL has become one of the most important factors affecting the quality of life of the elderly in our country. Therefore, hearing intervention for patients with ARHL plays a crucial role in improving their quality of life. At present, the use of hearing aids and cochlear implants are the main means to treat the daily hearing difficulties and communication difficulties of patients with ARHL. However, in China, due to the economy, the concept of not wanting to treat the elderly, and other reasons, the hearing aid wearing rate compared to developed countries has significant differences. Cochlear implant is another option for patients with presbyacusis, and patients can obtain good hearing and speech recognition rate after surgery. At present, there is no definitive conclusion on whether the quality of life of patients after cochlear implantation has been improved, and this study will be reviewed based on previous relevant reports.
PubMed: 38059171
DOI: No ID Found -
American Journal of Audiology Dec 2023This tutorial reviews effects of environmental stressors like blast overpressures and other well-known acoustic contaminants (continuous, intermittent, and impulsive...
PURPOSE
This tutorial reviews effects of environmental stressors like blast overpressures and other well-known acoustic contaminants (continuous, intermittent, and impulsive noise) on hearing, tinnitus, vestibular, and balance-related functions. Based on the overall outcome of these effects, detailed consideration is given to the health and well-being of individuals.
METHOD
Because hearing loss and tinnitus are consequential in affecting quality of life, novel neuromodulation paradigms are reviewed for their positive abatement and treatment-related effects. Examples of clinical data, research strategies, and methodological approaches focus on repetitive transcranial magnetic stimulation (TMS) and electrical stimulation of the vagus nerve paired with tones (VNS) for their unique contributions to this area.
RESULTS
Acoustic toxicants transmitted through the atmosphere are noteworthy for their propensity to induce hearing loss and tinnitus. Mounting evidence also indicates that high-level rapid onset changes in atmospheric sound pressure can significantly impact vestibular and balance function. Indeed, the risk of falling secondary to loss of, or damage to, sensory receptor cells in otolith organs (utricle and saccule) is a primary reason for this concern. As part of the complexities involved in VNS treatment strategies, vocal dysfunction may also manifest. In addition, evaluation of temporospatial gait parameters is worthy of consideration based on their ability to detect and monitor incipient neurological disease, cognitive decline, and mortality.
CONCLUSION
Highlighting these respective areas underscores the need to enhance information exchange among scientists, clinicians, and caregivers on the benefits and complications of these outcomes.
Topics: Humans; Tinnitus; Occupational Health; Military Personnel; Quality of Life; Hearing Loss; Deafness
PubMed: 37713532
DOI: 10.1044/2023_AJA-23-00125 -
Molecular Biology and Evolution Jul 2023The genetic bases underlying the evolution of morphological and functional innovations of the mammalian inner ear are poorly understood. Gene regulatory regions are...
The genetic bases underlying the evolution of morphological and functional innovations of the mammalian inner ear are poorly understood. Gene regulatory regions are thought to play an important role in the evolution of form and function. To uncover crucial hearing genes whose regulatory machinery evolved specifically in mammalian lineages, we mapped accelerated noncoding elements (ANCEs) in inner ear transcription factor (TF) genes and found that PKNOX2 harbors the largest number of ANCEs within its transcriptional unit. Using reporter gene expression assays in transgenic zebrafish, we determined that four PKNOX2-ANCEs drive differential expression patterns when compared with ortholog sequences from close outgroup species. Because the functional role of PKNOX2 in cochlear hair cells has not been previously investigated, we decided to study Pknox2 null mice generated by CRISPR/Cas9 technology. We found that Pknox2-/- mice exhibit reduced distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) thresholds at high frequencies together with an increase in peak 1 amplitude, consistent with a higher number of inner hair cells (IHCs)-auditory nerve synapsis observed at the cochlear basal region. A comparative cochlear transcriptomic analysis of Pknox2-/- and Pknox2+/+ mice revealed that key auditory genes are under Pknox2 control. Hence, we report that PKNOX2 plays a critical role in cochlear sensitivity at higher frequencies and that its transcriptional regulation underwent lineage-specific evolution in mammals. Our results provide novel insights about the contribution of PKNOX2 to normal auditory function and to the evolution of high-frequency hearing in mammals.
Topics: Animals; Mice; Cochlea; Hearing; Mammals; Mice, Knockout; Transcription Factors; Zebrafish
PubMed: 37247388
DOI: 10.1093/molbev/msad128 -
British Journal of Neurosurgery Oct 2023Malignant change in vestibular schwannoma is rare and intracranial metastatic deposits have not been reported.
BACKGROUND
Malignant change in vestibular schwannoma is rare and intracranial metastatic deposits have not been reported.
CLINICAL PRESENTATION
We report the case of a 64 year old woman with a benign vestibular schwannoma who underwent translabyrinthine excision in 1996 and Gamma Knife radiosurgery (Elekta AB, Stockholm, Sweden) (GKRS) in 2006. She presents 10 years after GKRS with progressive neurological deterioration. Histopathologic analysis confirms a malignant peripheral nerve sheath tumour, WHO grade IV with subsequent metastatic spread to the left thalamus confirmed on biopsy.
CONCLUSION
We report a rare case of a vestibular schwannoma metastasizing with histological confirmation. It also reminds us of malignant conversion of a benign vestibular schwannoma following GKRS and subsequent aggressive behaviour, with poor prognosis.
Topics: Female; Humans; Middle Aged; Neuroma, Acoustic; Radiosurgery
PubMed: 33686895
DOI: 10.1080/02688697.2021.1884650