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Proceedings of the National Academy of... Nov 2020Sounds are processed by the ear and central auditory pathway. These processing steps are biologically complex, and many aspects of the transformation from sound...
Sounds are processed by the ear and central auditory pathway. These processing steps are biologically complex, and many aspects of the transformation from sound waveforms to cortical response remain unclear. To understand this transformation, we combined models of the auditory periphery with various encoding models to predict auditory cortical responses to natural sounds. The cochlear models ranged from detailed biophysical simulations of the cochlea and auditory nerve to simple spectrogram-like approximations of the information processing in these structures. For three different stimulus sets, we tested the capacity of these models to predict the time course of single-unit neural responses recorded in ferret primary auditory cortex. We found that simple models based on a log-spaced spectrogram with approximately logarithmic compression perform similarly to the best-performing biophysically detailed models of the auditory periphery, and more consistently well over diverse natural and synthetic sounds. Furthermore, we demonstrated that including approximations of the three categories of auditory nerve fiber in these simple models can substantially improve prediction, particularly when combined with a network encoding model. Our findings imply that the properties of the auditory periphery and central pathway may together result in a simpler than expected functional transformation from ear to cortex. Thus, much of the detailed biological complexity seen in the auditory periphery does not appear to be important for understanding the cortical representation of sound.
Topics: Acoustic Stimulation; Animals; Auditory Cortex; Auditory Pathways; Auditory Perception; Cochlea; Cochlear Nerve; Ferrets; Humans; Models, Neurological; Neurons; Sound; Speech
PubMed: 33097665
DOI: 10.1073/pnas.1922033117 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Aug 2022Some patients with severe-profound sensorineural hearing loss (SNHL) with normal cochlear anatomical structure received cochlear implantation (CI) and the... (Review)
Review
Some patients with severe-profound sensorineural hearing loss (SNHL) with normal cochlear anatomical structure received cochlear implantation (CI) and the hearing and speech rehabilitation effect was not ideal. Through retrospective analysis, it was found that some of these patients had cochlear never canal (CNC) stenosis, or atresia in severe cases.This article reviews the development of the CNC, the diagnostic criteria of CNC stenosis and the results of hearing and speech rehabilitation in these patients after CI.
Topics: Cochlear Implantation; Cochlear Nerve; Constriction, Pathologic; Hearing Loss, Sensorineural; Humans; Retrospective Studies
PubMed: 35959587
DOI: 10.13201/j.issn.2096-7993.2022.08.016 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Nov 2020To investigate the distribution of common inner ear and internal auditory canal malformations in children with single-sided deafness(SSD) ,and to explore the imaging...
To investigate the distribution of common inner ear and internal auditory canal malformations in children with single-sided deafness(SSD) ,and to explore the imaging etiology of SSD by comparing the quantitative parameters of key bone structures between deaf and normal ears in children with congenital SSD. Forty children with SSD diagnosed in the Second Hospital of Lanzhou University from September 2016 to March 2019 were collected. All of them underwent HRCT examinations of temporal bone . The area of bone island, the width of vestibular, the width of internal auditory canal, the height of cochlear and the width of cochlear basal axis were measured. Paired t test was used to compare the difference between the hearing abnormality and normal hearing in children with SSD. The rate of inner ear deformity was 62.5% in SSD group,the most common deformity was cochlear nerve canal deformity, 20 cases (50.0%) of cochlear canal stenosis and 3 cases (7.5%) of cochlear canal atresia.The second most common deformity was internal auditory canal deformity, including 5 cases (12.5%) of internal auditory canal stenosis and 1 case (2.5%) of internal auditory canal atresia. Other malformations included 1 case(2.5%) of RO, 2 cases (5.0%) of incomplete partition (IP) type II and 1 case (2.5%) of enlargement of vestibular aqueduct (EVA). There are no significant difference in the measured results of the key structures of the inner ear between two groups except the width of cochlear nerve canal, internal auditory canal and the area of bone island. The main inner ear deformities in children with SSD are cochlear nerve canal stenosis and inner auditory canal stenosis. HRCT of temporal bone has high diagnostic value for inner ear deformities in children with SSD.
Topics: Child; Cochlea; Cochlear Nerve; Deafness; Hearing Loss, Sensorineural; Humans; Retrospective Studies; Temporal Bone; Tomography, X-Ray Computed; Vestibular Aqueduct
PubMed: 33254314
DOI: 10.13201/j.issn.2096-7993.2020.11.005 -
Hearing Research Sep 2020The electrically evoked compound action potential (eCAP) has been widely studied for its clinical value in evaluating cochlear implants (CIs). However, to date,...
OBJECTIVE
The electrically evoked compound action potential (eCAP) has been widely studied for its clinical value in evaluating cochlear implants (CIs). However, to date, single-fiber recordings have not been recorded from the human auditory nerve, and many unknowns remain about the firing properties that underlie the eCAP in patients with CIs. In particular, the temporal properties of auditory nerve fiber firing might contain valuable information that may be used to estimate the condition of the surviving auditory nerve fibers. This study aimed to evaluate the temporal properties of neural firing underlying human eCAPs with a new deconvolution model.
DESIGN
Assuming that each auditory nerve fiber produces the same unitary response (UR), the eCAP can be seen as a convolution of a UR with a compound discharge latency distribution (CDLD). We developed an iterative deconvolution model that derived a two-component Gaussian CDLD and a UR from recorded eCAPs. The choices were based on a deconvolution fitting error minimization routine (DMR). The DMR iteratively minimized the error between the recorded human eCAPs and the eCAPs simulated by the convolution of a parameterised UR and CDLD model (instead of directly deconvolving recorded eCAPs). Our new deconvolution model included two separate steps. In step one, the underlying URs of all eCAPs were derived, and the average of these URs was called the human UR. In step two, the CDLD was obtained by using the DMR in combination with the estimated human UR. With this model, we investigated the temporal firing properties of eCAPs by analysing the CDLDs, including the amplitudes, widths, peak latencies, and areas of CDLDs. The differences of the temporal properties in eCAPs between children and adults were explored. Finally, we validated the two-Gaussian component CDLD model with a multiple-Gaussian component CDLD model.
RESULTS
The estimated human UR contained a sharper, narrower negative component and a wider positive phase, compared to the previously described guinea pig UR. Furthermore, the eCAPs from humans could be predicted by the convolution of the human UR with a two-Gaussian component CDLD. The areas under CDLD (AUCD) reflected the number of excited nerve fibers over time. Both the CDLD magnitudes and AUCDs were significantly correlated with the eCAP amplitudes. Furthermore, different eCAPs with the same amplitude could lead to greatly different AUCDs. Significant differences of the temporal properties of eCAPs between children and adults were found. At last, the two-Gaussian component CDLD model was validated as the most optimal CDLD model.
CONCLUSION
This study described an iterative method that deconvolved human eCAPs into CDLDs, under the assumption that auditory nerve fibers had the same electrically evoked UR. Based on human eCAPs, we found a human UR that was different from the guinea pig UR. Furthermore, we found that CDLD characteristics revealed age-related temporal differences between human eCAPs. This temporal information may contain valuable clinical information on the survival and function of auditory nerve fibers. In turn, the surviving nerve condition might have prognostic value for speech outcomes in patients with CIs.
Topics: Animals; Cochlear Implantation; Cochlear Implants; Cochlear Nerve; Electric Stimulation; Evoked Potentials, Auditory; Guinea Pigs; Humans
PubMed: 32827881
DOI: 10.1016/j.heares.2020.108037 -
Otology & Neurotology : Official... Jul 2021Nimodipine has emerged as a promising strategy for protection of cranial nerves following vestibular schwannoma (VS) resections. Our goal was to conduct a comprehensive... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Nimodipine has emerged as a promising strategy for protection of cranial nerves following vestibular schwannoma (VS) resections. Our goal was to conduct a comprehensive analysis of clinical studies to determine the therapeutic efficacy of nimodipine in improving facial nerve and cochlear nerve function.
DATABASE REVIEWED
We searched PubMed, Scopus, Cochrane Clinical Trial Registry, Clinicaltrials.gov, World Health Organization's International Clinical Trials Registry Platform, and EU Clinical Trials Registry to identify clinical studies up to May 11, 2020.
METHODS
We included studies evaluating perioperative administration of nimodipine as a strategy to prevent or treat facial nerve or cochlear nerve dysfunction following VS resections. Primary outcomes included preservation or recovery of House-Brackman scale for facial nerve function and Hearing and Equilibrium Guidelines for cochlear nerve function at the latest follow-up visit. Secondary outcomes included adverse events and administration strategies of nimodipine.
RESULTS
Nine studies (603 patients) met inclusion, of which seven studies (559 patients) were included in the quantitative analysis. Overall, nimodipine significantly increased the odds of cranial nerve recovery compared with controls (odds ratio [OR] 2.87, 95% confidence intervals [CI] [2.08, 3.95]; I2 = 0%). Subgroup analysis demonstrated that nimodipine was only effective for cochlear nerve preservation (OR 2.78, 95% CI [1.74, 4.45]; I2 = 0%), but not for facial nerve function (OR 4.54, 95% CI [0.25, 82.42]; I2 = 33%).
CONCLUSION
Although there is evidence supporting the perioperative role of nimodipine for VS resections, more studies are warranted to help clarify the effects of nimodipine therapy on cranial nerve preservation.
Topics: Cochlear Nerve; Facial Nerve; Hearing; Hearing Tests; Humans; Nimodipine
PubMed: 33710143
DOI: 10.1097/MAO.0000000000003101 -
The Journal of the Acoustical Society... Dec 2021Although clinical use of the auditory brainstem response (ABR) to detect retrocochlear disorders has been largely replaced by imaging in recent years, the discovery of... (Review)
Review
Although clinical use of the auditory brainstem response (ABR) to detect retrocochlear disorders has been largely replaced by imaging in recent years, the discovery of cochlear synaptopathy has thrown this foundational measure of auditory function back into the spotlight. Whereas modern imaging now allows for the noninvasive detection of vestibular schwannomas, imaging technology is not currently capable of detecting cochlear synaptopathy, the loss of the synaptic connections between the inner hair cells and afferent auditory nerve fibers. However, animal models indicate that the amplitude of the first wave of the ABR, a far-field evoked potential generated by the synchronous firing of auditory nerve fibers, is highly correlated with synaptic integrity. This has led to many studies investigating the use of the ABR as a metric of synaptopathy in humans. However, these studies have yielded mixed results, leading to a lack of consensus about the utility of the ABR as an indicator of synaptopathy. This review summarizes the animal and human studies that have investigated the ABR as a measure of cochlear synaptic function, discusses factors that may have contributed to the mixed findings and the lessons learned, and provides recommendations for future use of this metric in the research and clinical settings.
Topics: Animals; Auditory Threshold; Cochlea; Cochlear Nerve; Evoked Potentials, Auditory, Brain Stem; Hearing Loss, Noise-Induced; Humans; Noise
PubMed: 34972291
DOI: 10.1121/10.0007484 -
Hearing Research Nov 2021Excess release of glutamate at the inner hair cell-type I auditory nerve synapse results in excitotoxicity characterized by rapid swelling and disintegration of the...
Excess release of glutamate at the inner hair cell-type I auditory nerve synapse results in excitotoxicity characterized by rapid swelling and disintegration of the afferent synapses, but in some cases, the damage expands to the spiral ganglion soma. Cochlear excitotoxic damage is largely mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) and kainate receptor (KAR) and potentially N-methyl-D-aspartate receptors (NMDAR). Because these receptors are developmentally regulated, the pattern of excitotoxic damage could change during development. To test this hypothesis, we compared AMPAR, NMDAR and KAR immunolabeling and excitotoxic damage patterns in rat postnatal day 3 (P3) and adult cochlear cultures. At P3, AMPAR and KAR immunolabeling, but not NMDAR, was abundantly expressed on peripheral nerve terminals adjacent to IHCs. In contrast, AMPAR, KAR and NMDAR immunolabeling was minimal or undetectable on the SGN soma. In adult rats, however, AMPAR, KAR and NMDAR immunolabeling occurred on both peripheral nerve terminals near IHCs as well as the soma of SGNs. High doses of Glu and KA only damaged peripheral nerve terminals near IHCs, but not SGNs, at P3, consistent with selective expression of AMPAR and KAR expression on the terminals. However, in adults, Glu and KA damaged both peripheral nerve terminals near IHCs and SGNs both of which expressed AMPAR and KAR. These results indicate that cochlear excitotoxic damage is closely correlated with structures that express AMPAR and KAR.
Topics: Animals; Glutamic Acid; Hair Cells, Auditory, Inner; Neurons; Rats; Receptors, N-Methyl-D-Aspartate; Spiral Ganglion; Up-Regulation; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
PubMed: 34607211
DOI: 10.1016/j.heares.2021.108358 -
Journal of Neural Engineering Apr 2023. Optogenetic stimulation of the auditory nerve offers the ability to overcome the limitations of cochlear implants through spatially precise stimulation, but cannot...
. Optogenetic stimulation of the auditory nerve offers the ability to overcome the limitations of cochlear implants through spatially precise stimulation, but cannot achieve the temporal precision nor temporal fidelity required for good hearing outcomes. Auditory midbrain recordings have indicated a combined (hybrid) stimulation approach may permit improvements in the temporal precision without sacrificing spatial precision by facilitating electrical activation thresholds. However, previous research has been conducted in undeafened or acutely deafened animal models, and the impact of chronic deafness remains unclear. Our study aims to compare the temporal precision of auditory nerve responses to optogenetic, electrical, and combined stimulation in acutely and chronically deafened animals.. We directly compare the temporal fidelity (measured as percentage of elicited responses) and precision (i.e. stability of response size and timing) of electrical, optogenetic, and hybrid stimulation (varying sub-threshold or supra-threshold optogenetic power levels combined with electrical stimuli) through compound action potential and single-unit recordings of the auditory nerve in transgenic mice expressing the opsin ChR2-H134R in auditory neurons. Recordings were conducted immediately or 2-3 weeks following aminoglycoside deafening when there was evidence of auditory nerve degeneration.. Results showed that responses to electrical stimulation had significantly greater temporal precision than optogenetic stimulation (< 0.001 for measures of response size and timing). This temporal precision could be maintained with hybrid stimulation, but only when the optogenetic stimulation power used was below or near activation threshold and worsened with increasing optical power. Chronically deafened mice showed poorer facilitation of electrical activation thresholds with concurrent optogenetic stimulation than acutely deafened mice. Additionally, responses in chronically deafened mice showed poorer temporal fidelity, but improved temporal precision to optogenetic and hybrid stimulation compared to acutely deafened mice.. These findings show that the improvement to temporal fidelity and temporal precision provided by a hybrid stimulation paradigm can also be achieved in chronically deafened animals, albeit at higher levels of concurrent optogenetic stimulation levels.
Topics: Animals; Mice; Deafness; Optogenetics; Cochlear Nerve; Cochlear Implants; Mice, Transgenic; Electric Stimulation; Cochlea; Acoustic Stimulation; Auditory Threshold
PubMed: 36963106
DOI: 10.1088/1741-2552/acc75f -
Stem Cell Reports Jan 2023Functional cochlear hair cells (HCs) innervated by spiral ganglion neurons (SGNs) are essential for hearing, whereas robust models that recapitulate the peripheral...
Functional cochlear hair cells (HCs) innervated by spiral ganglion neurons (SGNs) are essential for hearing, whereas robust models that recapitulate the peripheral auditory circuity are still lacking. Here, we developed cochlear organoids with functional peripheral auditory circuity in a staging three-dimensional (3D) co-culture system by initially reprogramming cochlear progenitor cells (CPCs) with increased proliferative potency that could be long-term expanded, then stepwise inducing the differentiation of cochlear HCs, as well as the outgrowth of neurites from SGNs. The function of HCs and synapses within organoids was confirmed by a series of morphological and electrophysiological evaluations. Single-cell mRNA sequencing revealed the differentiation trajectories of CPCs toward the major cochlear cell types and the dynamic gene expression during organoid HC development, which resembled the pattern of native HCs. We established the cochlear organoids with functional synapses for the first time, which provides a platform for deciphering the mechanisms of sensorineural hearing loss.
Topics: Cochlea; Spiral Ganglion; Neurons; Neurites; Organoids
PubMed: 36584686
DOI: 10.1016/j.stemcr.2022.11.024 -
The Journal of Physiology May 2021Ribbon-class synapses in the ear achieve analog to digital transformation of a continuously graded membrane potential to all-or-none spikes. In mammals, several auditory... (Review)
Review
Ribbon-class synapses in the ear achieve analog to digital transformation of a continuously graded membrane potential to all-or-none spikes. In mammals, several auditory nerve fibres (ANFs) carry information from each inner hair cell (IHC) to the brain in parallel. Heterogeneity of transmission among synapses contributes to the diversity of ANF sound-response properties. In addition to the place code for sound frequency and the rate code for sound level, there is also a temporal code. In series with cochlear amplification and frequency tuning, neural representation of temporal cues over a broad range of sound levels enables auditory comprehension in noisy multi-speaker settings. The IHC membrane time constant introduces a low-pass filter that attenuates fluctuations of the receptor potential above 1-2 kHz. The ANF spike generator adds a high-pass filter via its depolarization-rate threshold that rejects slow changes in the postsynaptic potential and its phasic response property that ensures one spike per depolarization. Synaptic transmission involves several stochastic subcellular processes between IHC depolarization and ANF spike generation, introducing delay and jitter that limits the speed and precision of spike timing. ANFs spike at a preferred phase of periodic sounds in a process called phase-locking that is limited to frequencies below a few kilohertz by both the IHC receptor potential and the jitter in synaptic transmission. During phase-locking to periodic sounds of increasing intensity, faster and facilitated activation of synaptic transmission and spike generation may be offset by presynaptic depletion of synaptic vesicles, resulting in relatively small changes in response phase. Here we review encoding of spike-timing at cochlear ribbon synapses.
Topics: Animals; Cochlea; Cochlear Nerve; Hair Cells, Auditory, Inner; Humans; Patient Discharge; Synapses
PubMed: 33644871
DOI: 10.1113/JP279189