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Developmental Cell Feb 2023Sound stimulus is encoded in mice by three molecularly and physiologically diverse subtypes of sensory neurons, called Ia, Ib, and Ic spiral ganglion neurons (SGNs)....
Sound stimulus is encoded in mice by three molecularly and physiologically diverse subtypes of sensory neurons, called Ia, Ib, and Ic spiral ganglion neurons (SGNs). Here, we show that the transcription factor Runx1 controls SGN subtype composition in the murine cochlea. Runx1 is enriched in Ib/Ic precursors by late embryogenesis. Upon the loss of Runx1 from embryonic SGNs, more SGNs take on Ia rather than Ib or Ic identities. This conversion was more complete for genes linked to neuronal function than to connectivity. Accordingly, synapses in the Ib/Ic location acquired Ia properties. Suprathreshold SGN responses to sound were enhanced in Runx1 mice, confirming the expansion of neurons with Ia-like functional properties. Runx1 deletion after birth also redirected Ib/Ic SGNs toward Ia identity, indicating that SGN identities are plastic postnatally. Altogether, these findings show that diverse neuronal identities essential for normal auditory stimulus coding arise hierarchically and remain malleable during postnatal development.
Topics: Animals; Mice; Cochlea; Spiral Ganglion; Sensory Receptor Cells; Synapses; Core Binding Factor Alpha 2 Subunit
PubMed: 36800995
DOI: 10.1016/j.devcel.2023.01.008 -
Ear and HearingPostimplantation facial nerve stimulation is a common side-effect of intracochlear electrical stimulation. Facial nerve stimulation occurs when electric current intended...
OBJECTIVES
Postimplantation facial nerve stimulation is a common side-effect of intracochlear electrical stimulation. Facial nerve stimulation occurs when electric current intended to stimulate the auditory nerve, spread beyond the cochlea to excite the nearby facial nerve, causing involuntarily facial muscle contractions. Facial nerve stimulation can often be resolved through adjustments in speech processor fitting but, in some instances, these measures exhibit limited benefit or may have a detrimental effect on speech perception. In this study, apical reference stimulation mode was investigated as a potential intervention to facial nerve stimulation. Apical reference stimulation is a bipolar stimulation strategy in which the most apical electrode is used as the reference electrode for stimulation on all the other intracochlear electrodes.
DESIGN
A person-specific model of the human cochlea, facial nerve and electrode array, coupled with a neural model, was used to predict excitation of auditory and facial nerve fibers. These predictions were used to evaluate the effectiveness in reducing facial nerve stimulation using apical reference stimulation. Predictions were confirmed in psychoacoustic tests by determining auditory comfort and threshold levels for the apical reference stimulation mode while capturing electromyography data in two participants.
RESULTS
Models predicted a favorable outcome for apical reference stimulation, as facial nerve fiber thresholds were higher and auditory thresholds were lower, in direct comparison to conventional monopolar stimulation. Psychophysical tests also illustrated decreased auditory thresholds and increased dynamic range during apical reference stimulation. Furthermore, apical reference stimulation resulted in lower electromyography energy levels, compared to conventional monopolar stimulation, which suggests a reduction in facial nerve stimulation. Subjective feedback corroborated that apical reference stimulation alleviated facial nerve stimulation.
CONCLUSION
Apical reference stimulation may be a viable strategy to alleviate facial nerve stimulation considering the improvements in dynamic range and auditory thresholds, complemented with a reduction in facial nerve stimulation symptoms.
Topics: Auditory Threshold; Cochlea; Cochlear Implants; Cochlear Nerve; Electric Stimulation; Facial Nerve; Humans
PubMed: 34923558
DOI: 10.1097/AUD.0000000000001170 -
Journal of the Association For Research... Dec 2022Cochlear implant (CI) recipients with preserved acoustic low-frequency hearing in the implanted ear are a growing group among traditional CI users who benefit from...
Cochlear implant (CI) recipients with preserved acoustic low-frequency hearing in the implanted ear are a growing group among traditional CI users who benefit from hybrid electric-acoustic stimulation (EAS). However, combined ipsilateral electric and acoustic stimulation also introduces interactions between the two modalities that can affect the performance of EAS users. A computational model of a single auditory nerve fiber that is excited by EAS was developed to study the interaction between electric and acoustic stimulation. Two existing models of sole electric or acoustic stimulation were coupled to simulate responses to combined EAS. Different methods of combining both models were implemented. In the coupled model variant, the refractoriness of the simulated fiber leads to suppressive interaction between electrically evoked and acoustically evoked spikes as well as spontaneous activity. The second model variant is an uncoupled EAS model without electric-acoustic interaction. By comparing predictions between the coupled and the noninteracting EAS model, it was possible to infer electric-acoustic interaction at the level of the auditory nerve. The EAS model was used to simulate fiber populations with realistic inter-unit variability, where each unit was represented by the single-fiber model. Predicted thresholds and dynamic ranges, spike rates, latencies, jitter, and vector strengths were compared to empirical data. The presented EAS model provides a framework for future studies of peripheral electric-acoustic interaction.
Topics: Acoustic Stimulation; Auditory Threshold; Cochlear Implants; Cochlear Implantation; Cochlear Nerve; Acoustics; Electric Stimulation; Computer Simulation; Speech Perception
PubMed: 36333573
DOI: 10.1007/s10162-022-00870-2 -
The Journal of Neuroscience : the... Aug 2022Exposure to nontraumatic noise drives long-lasting changes in auditory nerve synapses, which may influence hearing, but the induction mechanisms are not known. We...
Exposure to nontraumatic noise drives long-lasting changes in auditory nerve synapses, which may influence hearing, but the induction mechanisms are not known. We mimicked activity in acute slices of the cochlear nucleus from mice of both sexes by treating them with high potassium, after which voltage-clamp recordings from bushy cells indicated that auditory nerve synapses had reduced EPSC amplitude, quantal size, and vesicle release probability ( ). The effects of high potassium were prevented by blockers of nitric oxide (NO) synthase and protein kinase A. Treatment with the NO donor, PAPA-NONOate, also decreased , suggesting NO plays a central role in inducing synaptic changes. To identify the source of NO, we activated auditory nerve fibers specifically using optogenetics. Strobing for 2 h led to decreased EPSC amplitude and , which was prevented by antagonists against ionotropic glutamate receptors and NO synthase. This suggests that the activation of AMPA and NMDA receptors in postsynaptic targets of auditory nerve fibers drives release of NO, which acts retrogradely to cause long-term changes in synaptic function in auditory nerve synapses. This may provide insight into preventing or treating disorders caused by noise exposure. Auditory nerve fibers undergo long-lasting changes in synaptic properties in response to noise exposure , which may contribute to changes in hearing. Here, we investigated the cellular mechanisms underlying induction of synaptic changes using high potassium and optogenetic stimulation and identified important signaling pathways using pharmacology. Our results suggest that auditory nerve activity drives postsynaptic depolarization through AMPA and NMDA receptors, leading to the release of nitric oxide, which acts retrogradely to regulate presynaptic neurotransmitter release. These experiments revealed that auditory nerve synapses are unexpectedly sensitive to activity and can show dramatic, long-lasting changes in a few hours that could affect hearing.
Topics: Animals; Auditory Pathways; Cochlear Nerve; Cochlear Nucleus; Female; Male; Mice; Neuronal Plasticity; Nitric Oxide; Potassium; Receptors, N-Methyl-D-Aspartate; Synapses; Synaptic Transmission; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
PubMed: 35790402
DOI: 10.1523/JNEUROSCI.0666-22.2022 -
Hearing Research Mar 2021There are multiple etiologies and phenotypes of age-related hearing loss or presbyacusis. In this review we summarize findings from animal and human studies of... (Review)
Review
There are multiple etiologies and phenotypes of age-related hearing loss or presbyacusis. In this review we summarize findings from animal and human studies of presbyacusis, including those that provide the theoretical framework for distinct metabolic, sensory, and neural presbyacusis phenotypes. A key finding in quiet-aged animals is a decline in the endocochlear potential (EP) that results in elevated pure-tone thresholds across frequencies with greater losses at higher frequencies. In contrast, sensory presbyacusis appears to derive, in part, from acute and cumulative effects on hair cells of a lifetime of environmental exposures (e.g., noise), which often result in pronounced high frequency hearing loss. These patterns of hearing loss in animals are recognizable in the human audiogram and can be classified into metabolic and sensory presbyacusis phenotypes, as well as a mixed metabolic+sensory phenotype. However, the audiogram does not fully characterize age-related changes in auditory function. Along with the effects of peripheral auditory system declines on the auditory nerve, primary degeneration in the spiral ganglion also appears to contribute to central auditory system aging. These inner ear alterations often correlate with structural and functional changes throughout the central nervous system and may explain suprathreshold speech communication difficulties in older adults with hearing loss. Throughout this review we highlight potential methods and research directions, with the goal of advancing our understanding, prevention, diagnosis, and treatment of presbyacusis.
Topics: Aged; Aging; Animals; Auditory Threshold; Cochlear Nerve; Deafness; Hair Cells, Auditory; Hearing; Humans; Presbycusis
PubMed: 33189490
DOI: 10.1016/j.heares.2020.108109 -
Hearing Research Oct 2022It is well known that ageing and noise exposure are important causes of sensorineural hearing loss, and can result in damage of the outer hair cells or other structures...
It is well known that ageing and noise exposure are important causes of sensorineural hearing loss, and can result in damage of the outer hair cells or other structures of the inner ear, including synaptic damage to the auditory nerve (AN), i.e., cochlear synaptopathy (CS). Despite the suspected high prevalence of CS among people with self-reported hearing difficulties but seemingly normal hearing, conventional hearing-aid algorithms do not compensate for the functional deficits associated with CS. Here, we present and evaluate a number of auditory signal-processing strategies designed to maximally restore AN coding for listeners with CS pathologies. We evaluated our algorithms in subjects with and without suspected age-related CS to assess whether physiological and behavioural markers associated with CS can be improved. Our data show that after applying our algorithms, envelope-following responses and perceptual amplitude-modulation sensitivity were consistently enhanced in both young and older listeners. Speech-in-noise intelligibility showed small improvements after processing but mostly for young normal-hearing participants, with median improvements of up to 8.3%. Since our hearing-enhancement strategies were designed to optimally drive the AN fibres, they were able to improve temporal-envelope processing for listeners both with and without suspected CS. Our proposed algorithms can be rapidly executed and can thus extend the application range of current hearing aids and hearables, while leaving sound amplification unaffected.
Topics: Auditory Threshold; Cochlea; Cochlear Nerve; Hearing; Humans; Noise; Speech Perception
PubMed: 35961207
DOI: 10.1016/j.heares.2022.108569 -
European Archives of... Jul 2024The purpose of this retrospective study is to compare the results of electrically evoked compound action potential (ECAP) measurements using automatic auditory response... (Comparative Study)
Comparative Study
PURPOSE
The purpose of this retrospective study is to compare the results of electrically evoked compound action potential (ECAP) measurements using automatic auditory response telemetry (AutoART) with those obtained by ART in adults. The study also aimed to evaluate the predictive value of intraoperative ART and AutoART ECAPs for speech intelligibility (SI) and hearing success (HS), and to determine if cochlear nerve (CN) cross-sectional area (CSA) obtained preoperatively by magnetic resonance imaging (MRI) scans could predict ART and AutoART ECAPs and SI and HS outcome.
METHODS
The study analyzed and correlated ART and AutoART ECAP thresholds at electrodes E2, E6, and E10, as well as averaged ECAP thresholds over electrodes E1-E12, using data from 32 implants. Correlations were also examined for ART and AutoART ECAP slopes. In addition, averaged ART and AutoART ECAP thresholds and slopes over all 12 electrodes for each participant were correlated with CN CSA measured from MRI sequences. SI of the monosyllabic Freiburg Speech Test at 65 dB sound pressure level was examined along with averaged ART and AutoART thresholds and slopes over all 12 electrodes. A parallel analysis was performed for HS, derived from the difference between baseline and 6-month SI. Finally, correlations between CN CSA and SI, as well as CN CSA and HS were examined.
RESULTS
The results of the study showed a significant positive correlation between ART and AutoART ECAP thresholds and as well as slopes for E2, E6, E10 and averaged thresholds and slopes of E1-E12. However, no significant correlation was observed between ART and AutoART averaged ECAP thresholds and slopes and either SI and HS or CN CSA. Furthermore, no significant correlation was found between CN CSA and SI and HS.
CONCLUSION
While AutoART is a reliable and safe program for measuring ECAPs in adults, the study found no preoperative prognostic information on intraoperative ECAP results using parameters extracted from current MRI sequences or pre-/intraoperative information on subsequent hearing outcome using ECAP and CN CSA.
Topics: Humans; Cochlear Nerve; Retrospective Studies; Male; Middle Aged; Female; Adult; Cochlear Implants; Aged; Magnetic Resonance Imaging; Evoked Potentials, Auditory; Cochlear Implantation; Telemetry; Speech Intelligibility; Young Adult; Predictive Value of Tests; Auditory Threshold; Action Potentials
PubMed: 38219245
DOI: 10.1007/s00405-023-08444-5 -
The Eurasian Journal of Medicine Oct 2023The aim of this study is to evaluate the relationship between the cochlear nerve and the anatomical structures of the cochlea and internal acoustic canal in patients...
OBJECTIVE
The aim of this study is to evaluate the relationship between the cochlear nerve and the anatomical structures of the cochlea and internal acoustic canal in patients with congenital hearing loss.
MATERIALS AND METHODS
Temporal tomography and magnetic resonance images of 44 patients (88 ears) with non-syndromic congenital hearing loss were retrospectively analyzed between 2018 and 2021. Patients were divided into 2 groups according to cochlear nerve hypoplasia. Cochlear nerve canal width, cochlear basal/ middle turn widths, and internal auditory canal widths were examined.
RESULTS
Cochlear nerve hypoplasia was detected in 18.2% (n=16) of the patients and all of the patients with cochlear nerve hypoplasia had severe hearing loss. A statistically significant difference was found between the structures' widths in patients with and without cochlear nerve hypoplasia, in cochlear nerve canal and coronal width of the internal auditory canal. When stenosis is accepted as <1.4 mm for cochlear nerve canal and <3.80 mm for coronal width of the internal auditory canal, cochlear nerve hypoplasia differs statistically between the groups in measurements (respectively; P < .001, P=.018).
CONCLUSIONS
In patients with sensorineural hearing loss, cochlear nerve hypoplasia may accompany. Anatomical structures are important in predicting cochlear nerve hypoplasia from temporal computed tomography. Cochlear nerve hypoplasia should be suspected if the cochlear nerve canal and coronal width of the internal auditory canal are less than 1.4 mm and 3.8 mm, respectively, on temporal computed tomography.
PubMed: 37909185
DOI: 10.5152/eurasianjmed.2023.22196 -
Hearing Research Sep 2020Hearing impairment is a major health and economic concern worldwide. Currently, the cochlear implant (CI) is the standard of care for remediation of severe to profound... (Review)
Review
Hearing impairment is a major health and economic concern worldwide. Currently, the cochlear implant (CI) is the standard of care for remediation of severe to profound hearing loss, and in general, contemporary CIs are highly successful. But there is great variability in outcomes among individuals, especially in children, with many CI users deriving much less or even marginal benefit. Much of this variability is related to differences in auditory nerve survival, and there has been substantial interest in recent years in exploring potential therapies to improve survival of the cochlear spiral ganglion neurons (SGN) after deafness. Preclinical studies using osmotic pumps and other approaches in deafened animal models to deliver neurotrophic factors (NTs) directly to the cochlea have shown promising results, especially with Brain-Derived Neurotrophic Factor (BDNF). More recent studies have focused on the use of NT gene therapy to force expression of NTs by target cells within the cochlea. This could provide the means for a one-time treatment to promote long-term NT expression and improve neural survival after deafness. This review summarizes the evidence for the efficacy of exogenous NTs in preventing SGN degeneration after hearing loss and reviews the animal research to date suggesting that NT gene therapy can elicit long-term NT expression in the cochlea, resulting in significantly improved SGN and radial nerve fiber survival after deafness. In addition, we discuss NT gene therapy in other non-auditory applications and consider some of the remaining issues with regard to selecting optimal vectors, timing of treatment, and place/method of delivery, etc. that must be resolved prior to considering clinical application.
Topics: Animals; Brain-Derived Neurotrophic Factor; Deafness; Genetic Therapy; Humans; Neurons; Neurotrophin 3; Spiral Ganglion
PubMed: 32331858
DOI: 10.1016/j.heares.2020.107955 -
Neurobiology of Disease Oct 2023Age-related hearing loss (ARHL) is a prevalent condition affecting millions of individuals globally. This study investigated the role of the cell survival regulator Bcl2...
Age-related hearing loss (ARHL) is a prevalent condition affecting millions of individuals globally. This study investigated the role of the cell survival regulator Bcl2 in ARHL through in vitro and in vivo experiments and metabolomics analysis. The results showed that the lack of Bcl2 in the auditory cortex affects lipid metabolism, resulting in reduced synaptic function and neurodegeneration. Immunohistochemical analysis demonstrated enrichment of Bcl2 in specific areas of the auditory cortex, including the secondary auditory cortex, dorsal and ventral areas, and primary somatosensory cortex. In ARHL rats, a significant decrease in Bcl2 expression was observed in these areas. RNAseq analysis showed that the downregulation of Bcl2 altered lipid metabolism pathways within the auditory pathway, which was further confirmed by metabolomics analysis. These results suggest that Bcl2 plays a crucial role in regulating lipid metabolism, synaptic function, and neurodegeneration in ARHL; thereby, it could be a potential therapeutic target. We also revealed that Bcl2 probably has a close connection with lipid peroxidation and reactive oxygen species (ROS) production occurring in cochlear hair cells and cortical neurons in ARHL. The study also identified changes in hair cells, spiral ganglion cells, and nerve fiber density as consequences of Bcl2 deficiency, which could potentially contribute to the inner ear nerve blockage and subsequent hearing loss. Therefore, targeting Bcl2 may be a promising potential therapeutic intervention for ARHL. These findings provide valuable insights into the molecular mechanisms underlying ARHL and may pave the way for novel treatment approaches for this prevalent age-related disorder.
Topics: Animals; Rats; Aging; Lipid Metabolism; Neurons; Presbycusis; Spiral Ganglion
PubMed: 37813166
DOI: 10.1016/j.nbd.2023.106320