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PloS One 2023High-altitude (HA) affects sensory organ response, but its effects on the inner ear are not fully understood. The present scoping review aimed to collect the available... (Meta-Analysis)
Meta-Analysis
PURPOSE
High-altitude (HA) affects sensory organ response, but its effects on the inner ear are not fully understood. The present scoping review aimed to collect the available evidence about HA effects on the inner ear with focus on auditory function.
METHODS
The scoping review was conducted following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for scoping reviews. PubMed, Scopus, and Web of Science electronic databases were systematically searched to identify studies conducted in the last 20 years, which quantified in healthy subjects the effects of HA on auditory function.
RESULTS
The systematic search identified 17 studies on a total population of 888 subjects (88.7% male, age: 27.8 ± 4.1 years; median sample size of 15 subjects). Nine studies were conducted in a simulated environment and eight during real expeditions at HA. To quantify auditory function, six studies performed pure tone audiometry, four studies measured otoacoustic emissions (OAE) and eight studies measured auditory evoked responses (AER). Study protocols presented heterogeneity in the spatio-temporal patterns of HA exposure, with highly varying maximal altitudes and exposure durations.
CONCLUSION
Most studies reported a reduction of auditory function with HA in terms of either elevation of auditory thresholds, lengthening of AER latencies, reduction of distortion-product and transient-evoked OAEs. Future studies in larger populations, using standardized protocols and multi-technique auditory function evaluation, are needed to further characterize the spatio-temporal pattern of HA effects along the auditory pathways and clarify the pathophysiological implications and reversibility of the observed changes.
Topics: Humans; Male; Young Adult; Adult; Female; Altitude; Hearing; Otoacoustic Emissions, Spontaneous; Auditory Pathways; Altitude Sickness
PubMed: 37733697
DOI: 10.1371/journal.pone.0291919 -
Communications Biology Nov 2023Both classic and contemporary models of auditory word repetition involve at least four left hemisphere regions: primary auditory cortex for processing sounds; pSTS...
Both classic and contemporary models of auditory word repetition involve at least four left hemisphere regions: primary auditory cortex for processing sounds; pSTS (within Wernicke's area) for processing auditory images of speech; pOp (within Broca's area) for processing motor images of speech; and primary motor cortex for overt speech articulation. Previous functional-MRI (fMRI) studies confirm that auditory repetition activates these regions, in addition to many others. Crucially, however, contemporary models do not specify how regions interact and drive each other during auditory repetition. Here, we used dynamic causal modelling, to test the functional interplay among the four core brain regions during single auditory word and pseudoword repetition. Our analysis is grounded in the principle of degeneracy-i.e., many-to-one structure-function relationships-where multiple neural pathways can execute the same function. Contrary to expectation, we found that, for both word and pseudoword repetition, (i) the effective connectivity between pSTS and pOp was predominantly bidirectional and inhibitory; (ii) activity in the motor cortex could be driven by either pSTS or pOp; and (iii) the latter varied both within and between individuals. These results suggest that different neural pathways can support auditory speech repetition. This degeneracy may explain resilience to functional loss after brain damage.
Topics: Humans; Speech; Brain; Motor Cortex; Brain Mapping; Models, Neurological
PubMed: 37957231
DOI: 10.1038/s42003-023-05515-5 -
Advanced Science (Weinheim,... Jan 2024Compared with individuals with hearing loss, tinnitus patients without hearing loss have more psychological or emotional problems. Tinnitus is closely associated to...
Compared with individuals with hearing loss, tinnitus patients without hearing loss have more psychological or emotional problems. Tinnitus is closely associated to abnormal metabolism and function of the limbic system, a key brain region for emotion experience, but the underlying molecular mechanism remains unknown. Using whole-brain microvasculature dynamics imaging, the anterior cingulate cortex (ACC) is identified as a key brain region of limbic system involve in the onset of salicylate-induced tinnitus in mice. In the tinnitus group, there is enhanced purine metabolism, oxidative phosphorylation, and a distinct pattern of phosphorylation in glutamatergic synaptic pathway according to the metabolome profiles, quantitative proteomic, and phosphoproteomic data of mice ACC tissue. Electroencephalogram in tinnitus patients with normal hearing thresholds show that the functional connectivity between pregenual anterior cingulate cortex and the primary auditory cortex is significantly increased for high-gamma frequency band, which is positively correlated with the serum glutamate level. These findings indicate that ACC plays an important role in the pathophysiology of tinnitus by interacting with the primary auditory cortex and provide potential molecular targets in the ACC for tinnitus treatment.
Topics: Humans; Mice; Animals; Gyrus Cinguli; Tinnitus; Proteomics; Hearing Loss; Electroencephalography
PubMed: 38009798
DOI: 10.1002/advs.202304709 -
BioRxiv : the Preprint Server For... Oct 2023The cochlear nuclear complex (CN) is the starting point for all central auditory processing and comprises a suite of neuronal cell types that are highly specialized for...
The cochlear nuclear complex (CN) is the starting point for all central auditory processing and comprises a suite of neuronal cell types that are highly specialized for neural coding of acoustic signals. To examine how their striking functional specializations are determined at the molecular level, we performed single-nucleus RNA sequencing of the mouse CN to molecularly define all constituent cell types and related them to morphologically- and electrophysiologically-defined neurons using Patch-seq. We reveal an expanded set of molecular cell types encompassing all previously described major types and discover new subtypes both in terms of topographic and cell-physiologic properties. Our results define a complete cell-type taxonomy in CN that reconciles anatomical position, morphological, physiological, and molecular criteria. This high-resolution account of cellular heterogeneity and specializations from the molecular to the circuit level illustrates molecular underpinnings of functional specializations and enables genetic dissection of auditory processing and hearing disorders with unprecedented specificity.
PubMed: 37293040
DOI: 10.1101/2023.05.15.539065 -
Frontiers in Neural Circuits 2023The cochlear nucleus (CN) is often regarded as the gateway to the central auditory system because it initiates all ascending pathways. The CN consists of dorsal and...
The cochlear nucleus (CN) is often regarded as the gateway to the central auditory system because it initiates all ascending pathways. The CN consists of dorsal and ventral divisions (DCN and VCN, respectively), and whereas the DCN functions in the analysis of spectral cues, circuitry in VCN is part of the pathway focused on processing binaural information necessary for sound localization in horizontal plane. Both structures project to the inferior colliculus (IC), which serves as a hub for the auditory system because pathways ascending to the forebrain and descending from the cerebral cortex converge there to integrate auditory, motor, and other sensory information. DCN and VCN terminations in the IC are thought to overlap but given the differences in VCN and DCN architecture, neuronal properties, and functions in behavior, we aimed to investigate the pattern of CN connections in the IC in more detail. This study used electrophysiological recordings to establish the frequency sensitivity at the site of the anterograde dye injection for the VCN and DCN of the CBA/CaH mouse. We examined their contralateral projections that terminate in the IC. The VCN projections form a topographic sheet in the central nucleus (CNIC). The DCN projections form a tripartite set of laminar sheets; the lamina in the CNIC extends into the dorsal cortex (DC), whereas the sheets to the lateral cortex (LC) and ventrolateral cortex (VLC) are obliquely angled away. These fields in the IC are topographic with low frequencies situated dorsally and progressively higher frequencies lying more ventrally and/or laterally; the laminae nestle into the underlying higher frequency fields. The DCN projections are complementary to the somatosensory modules of layer II of the LC but both auditory and spinal trigeminal terminations converge in the VLC. While there remains much to be learned about these circuits, these new data on auditory circuits can be considered in the context of multimodal networks that facilitate auditory stream segregation, signal processing, and species survival.
Topics: Mice; Animals; Inferior Colliculi; Cochlear Nucleus; Auditory Pathways; Mice, Inbred CBA; Neurons
PubMed: 37554670
DOI: 10.3389/fncir.2023.1229746 -
Advanced Science (Weinheim,... Mar 2024There are no Food and Drug Administration-approved drugs for treating noise-induced hearing loss (NIHL), reflecting the absence of clear specific therapeutic targets and...
There are no Food and Drug Administration-approved drugs for treating noise-induced hearing loss (NIHL), reflecting the absence of clear specific therapeutic targets and effective delivery strategies. Noise trauma is demonstrated results in nicotinamide adenine dinucleotide (NAD+) downregulation and mitochondrial dysfunction in cochlear hair cells (HCs) and spiral ganglion neurons (SGNs) in mice, and NAD+ boosted by nicotinamide (NAM) supplementation maintains cochlear mitochondrial homeostasis and prevents neuroexcitatory toxic injury in vitro and ex vivo, also significantly ameliorated NIHL in vivo. To tackle the limited drug delivery efficiency due to sophisticated anatomical barriers and unique clearance pathway in ear, personalized NAM-encapsulated porous gelatin methacryloyl (PGMA@NAM) are developed based on anatomy topography of murine temporal bone by micro-computed tomography and reconstruction of round window (RW) niche, realizing hydrogel in situ implantation completely, NAM sustained-release and long-term auditory preservation in mice. This study strongly supports personalized PGMA@NAM as NIHL protection drug with effective inner ear delivery, providing new inspiration for drug-based treatment of NIHL.
Topics: Mice; Animals; Hearing Loss, Noise-Induced; Niacinamide; NAD; Delayed-Action Preparations; Porosity; X-Ray Microtomography; Gelatin; Methacrylates
PubMed: 38225752
DOI: 10.1002/advs.202305682 -
Journal of Cellular and Molecular... Apr 2024Ferroptosis, characterized by iron-dependent lipid reactive oxygen species (ROS) accumulation, plays a pivotal role in cisplatin-induced ototoxicity. Existing research...
Ferroptosis, characterized by iron-dependent lipid reactive oxygen species (ROS) accumulation, plays a pivotal role in cisplatin-induced ototoxicity. Existing research has suggested that in cisplatin-mediated damage to auditory cells and hearing loss, ferroptosis is partially implicated. 4-Octyl itaconate (4-OI), derived from itaconic acid, effectively permeates cell membranes, showcasing potent anti-inflammatory as well as antioxidant effects in several disease models. Our study aimed to investigate the effect of 4-OI on cisplatin-induced ferroptosis and the underlying molecular mechanisms. The survival rates of HEI-OC1 cells and mice cochlea hair cells were measured by CCK8 and immunofluorescence, respectively. The auditory brainstem response (ABR) audiometry was used to detect changes in hearing thresholds in mice before and after treatment. Levels of ROS were evaluated by DCFH-DA. Real-time PCR quantified inflammatory cytokines TNF-α, IL-6 and IL-1β. Network Pharmacology and RNA sequencing (RNA-seq) analysis of the potential mechanism of 4-OI resistance to cisplatin-induced ferroptosis. The expressions of ferroptosis-related factors (GPX4, SLC7A11 and PTGS2) and important antioxidant factors (NRF2, HO-1, GCLC and NQO1) were tested by real-time PCR, Western blot and immunofluorescence. Results demonstrated cisplatin-induced significant ROS and inflammatory factor release, reduced NRF2 expression, hindered nuclear translocation and activated ferroptosis. Pretreatment with 4-OI exhibited anti-inflammatory and antioxidant effects, along with resistance to ferroptosis, ultimately mitigating cisplatin-induced cell loss. In the present study, we show that 4-OI inhibits cisplatin-induced ferroptosis possibly through activation of the NRF2/HO-1 signalling pathway, thereby exerting a protective effect against cisplatin-induced damage to auditory cells, and providing a new therapeutic strategy for cisplatin-induced hearing loss.
Topics: Animals; Mice; Cisplatin; NF-E2-Related Factor 2; Reactive Oxygen Species; Antioxidants; Ferroptosis; Apoptosis; Hearing Loss; Anti-Inflammatory Agents; Succinates
PubMed: 38506087
DOI: 10.1111/jcmm.18207 -
Brain Stimulation 2023Cochlear implants (CIs) restore activity in the deafened auditory system via electrical stimulation of the auditory nerve. As the spread of electric current in...
Cochlear implants (CIs) restore activity in the deafened auditory system via electrical stimulation of the auditory nerve. As the spread of electric current in biological tissues is rather broad, the spectral information provided by electrical CIs is limited. Optogenetic stimulation of the auditory nerve has been suggested for artificial sound coding with improved spectral selectivity, as light can be conveniently confined in space. Yet, the foundations for optogenetic sound coding strategies remain to be established. Here, we parametrized stimulus-response-relationships of the auditory pathway in gerbils for optogenetic stimulation. Upon activation of the auditory pathway by waveguide-based optogenetic stimulation of the spiral ganglion, we recorded neuronal activity of the auditory midbrain, in which neural representations of spectral, temporal, and intensity information can be found. Screening a wide range of optical stimuli and taking the properties of optical CI emitters into account, we aimed to optimize stimulus paradigms for potent and energy-efficient activation of the auditory pathway. We report that efficient optogenetic coding builds on neural integration of millisecond stimuli built from microsecond light pulses, which optimally accommodate power-efficient laser diode operation. Moreover, we performed an activity-level-dependent comparison of optogenetic and acoustic stimulation in order to estimate the dynamic range and the maximal stimulation intensity amenable to single channel optogenetic sound encoding, and indicate that it complies well with speech comprehension in a typical conversation (65 dB). Our results provide a first framework for the development of coding strategies for future optogenetic hearing restoration.
Topics: Auditory Pathways; Optogenetics; Cochlear Implantation; Cochlear Implants; Mesencephalon; Acoustic Stimulation; Electric Stimulation
PubMed: 37778456
DOI: 10.1016/j.brs.2023.09.018 -
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 -
Frontiers in Integrative Neuroscience 2023Occupational workers are increasingly aware of the risk of noise overexposure to the auditory system but lack awareness about potential risks to the vestibular system....
INTRODUCTION
Occupational workers are increasingly aware of the risk of noise overexposure to the auditory system but lack awareness about potential risks to the vestibular system. The purpose of this study was to investigate changes in vestibular end organ function in a known at-risk noise-exposed population, firefighters compared to age- and sex-matched controls using electrophysiologic measures of cervical vestibular evoked myogenic potentials (cVEMP).
METHODS
A cross-sectional observational study compared cVEMP response characteristics in 38 noise-exposed firefighters. Firefighters were grouped by years of exposure in the fire service. The cVEMP responses were compared within firefighter groups and between firefighters and age- and sex-matched controls. Dependent variables included the response characteristics of amplitude, latency and threshold.
RESULTS
cVEMP response amplitudes were significantly decreased in firefighters compared to their age- and sex-matched controls. Threshold of the cVEMP responses were significantly higher in firefighters compared to controls and firefighters had a higher incidence of absent cVEMP responses compared to controls. Response amplitudes decreased with increasing years in the fire-service at an increased rate compared to their age- and sex-matched controls. Latency of the cVEMP response was not significantly different in firefighters compared to controls. These findings are consistent with both animal and human studies suggesting noise-induced changes in the sacculocollic pathway.
DISCUSSION
In the absence of any reported vestibular symptoms or auditory indicators of noise-induced hearing loss, these early effects on the vestibular system point to a potential hidden vestibular loss.
PubMed: 37849955
DOI: 10.3389/fnint.2023.1236661