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Journal of the Association For Research... Dec 2022In the avian auditory brain stem, acoustic timing and intensity cues are processed in separate, parallel pathways via the two divisions of the cochlear nucleus, nucleus...
In the avian auditory brain stem, acoustic timing and intensity cues are processed in separate, parallel pathways via the two divisions of the cochlear nucleus, nucleus angularis (NA) and nucleus magnocellularis (NM). Differences in excitatory and inhibitory synaptic properties, such as release probability and short-term plasticity, contribute to differential processing of the auditory nerve inputs. We investigated the distribution of synaptotagmin, a putative calcium sensor for exocytosis, via immunohistochemistry and double immunofluorescence in the embryonic and hatchling chick brain stem (Gallus gallus). We found that the two major isoforms, synaptotagmin 1 (Syt1) and synaptotagmin 2 (Syt2), showed differential expression. In the NM, anti-Syt2 label was strong and resembled the endbulb terminals of the auditory nerve inputs, while anti-Syt1 label was weaker and more punctate. In NA, both isoforms were intensely expressed throughout the neuropil. A third isoform, synaptotagmin 7 (Syt7), was largely absent from the cochlear nuclei. In nucleus laminaris (NL, the target nucleus of NM), anti-Syt2 and anti-Syt7 strongly labeled the dendritic lamina. These patterns were established by embryonic day 18 and persisted to postnatal day 7. Double-labeling immunofluorescence showed that Syt1 and Syt2 were associated with vesicular glutamate transporter 2 (VGluT2), but not vesicular GABA transporter (VGAT), suggesting that these Syt isoforms were localized to excitatory, but not inhibitory, terminals. These results suggest that Syt2 is the major calcium binding protein underlying excitatory neurotransmission in the timing pathway comprising NM and NL, while Syt2 and Syt1 regulate excitatory transmission in the parallel intensity pathway via cochlear nucleus NA.
Topics: Animals; Calcium; Chickens; Cochlear Nerve; Cochlear Nucleus; Synaptotagmin II; Neurotransmitter Agents; Auditory Pathways; Synaptic Transmission
PubMed: 35999323
DOI: 10.1007/s10162-022-00863-1 -
Audiology & Neuro-otology 2021In this study, optic coherence tomography (OCT) examination was performed to check whether there was any interaction between ophthalmic axonal structures in unilateral...
An Evaluation of the Relationship between Retinal Nerve Fiber Thickness, Cochlear Nerve Thickness, the Level of Tinnitus, and Hearing Loss in Unilateral Tinnitus Patients.
BACKGROUND
In this study, optic coherence tomography (OCT) examination was performed to check whether there was any interaction between ophthalmic axonal structures in unilateral tinnitus patients, and the relationship between optic nerve thickness and cochlear nerve thickness was evaluated.
OBJECTIVE
The aim of the study was to evaluate the relatioship between hearing loss, tinnitus, and nerve thicknesses.
STUDY DESIGN
Prospective study.
SETTING
Tertiary referral university hospital.
PATIENTS
The study included 88 patients with unilateral tinnitus, for which no organic cause could be found in physical examination, psychiatric evaluation, or with imaging methods. Study groups were formed of the tinnitus side and control groups were formed of the healthy side as follows: Group 1 (Non-tinnitus side normal hearing values - n = 30), Group 2 (non-tinnitus side minimal hearing loss - n = 27), Group 3 (non-tinnitus side moderate hearing loss - n = 31), Group 4 (tinnitus side normal hearing values - n = 25), Group 5 (tinnitus side minimal hearing loss - n = 25), and Group 6 (tinnitus side moderate hearing loss - n = 38).
INTERVENTION
Retinal nerve fiber layer (RNFL) thickness was evaluated with OCT, and the cochlear nerve cross-sectional area was evaluated with MRI.
MAIN OUTCOME MEASURES
RNFL measurements were taken with OCT from the subfoveal area (RNFL-SF) and 1.5 mm temporal to the fovea (RNFL-T µm) and nasal (RNFL-N µm) sectors. On MRI, 3 measurements were taken along the nerve from the cerebellopontine angle as far as the internal auditory canal, and the mean value of these 3 measurements was calculated.
RESULTS
When the groups were evaluated in respect of cochlear nerve thickness, a significant difference was seen between Group 1 and both the groups with hearing loss and the tinnitus groups. In the subgroup analysis, a statistically significant difference was determined between Group 1 and Groups 3, 4, 5, and 6 (p = 0.013, p = 0.003, p < 0.001, and p < 0.001, respectively). When the groups were evaluated in respect of the RNFL-SF (µm), RNFL-T (µm), and RNFL-N (µm) values, the differences were determined to be statistically significant (p < 0.001 for all). In the correlation analysis, a negative correlation was determined between hearing loss and cochlear nerve diameter (r: -0.184, p = 0.014), and RNFL-N (r: -0.272, p < 0.001) and between tinnitus and cochlear nerve diameter (r: -0.536, p < 0.001), and RNFL-T (r: -0.222, p < 0.009).
CONCLUSION
The study results clearly showed a relationship between cochlear nerve fiber thickness and hearing loss and the severity of tinnitus in cases with unilateral tinnitus and that there could be neurodegenerative factors in the disease etiology. A similar relationship seen with the RNFL supports the study hypothesis.
Topics: Cochlear Nerve; Hearing Loss; Humans; Nerve Fibers; Optic Disk; Prospective Studies; Retinal Ganglion Cells; Tinnitus; Tomography, Optical Coherence
PubMed: 33626543
DOI: 10.1159/000512004 -
Scientific Reports Oct 2019Noninvasive transcranial electric stimulation is increasingly being used as an advantageous therapy alternative that may activate deep tissues while avoiding drug...
Noninvasive transcranial electric stimulation is increasingly being used as an advantageous therapy alternative that may activate deep tissues while avoiding drug side-effects. However, not only is there limited evidence for activation of deep tissues by transcranial electric stimulation, its evoked human sensation is understudied and often dismissed as a placebo or secondary effect. By systematically characterizing the human sensation evoked by transcranial alternating-current stimulation, we observed not only stimulus frequency and electrode position dependencies specific for auditory and visual sensation but also a broader presence of somatic sensation ranging from touch and vibration to pain and pressure. We found generally monotonic input-output functions at suprathreshold levels, and often multiple types of sensation occurring simultaneously in response to the same electric stimulation. We further used a recording circuit embedded in a cochlear implant to directly and objectively measure the amount of transcranial electric stimulation reaching the auditory nerve, a deep intercranial target located in the densest bone of the skull. We found an optimal configuration using an ear canal electrode and low-frequency (<300 Hz) sinusoids that delivered maximally ~1% of the transcranial current to the auditory nerve, which was sufficient to produce sound sensation even in deafened ears. Our results suggest that frequency resonance due to neuronal intrinsic electric properties need to be explored for targeted deep brain stimulation and novel brain-computer interfaces.
Topics: Adult; Aged; Auditory Perception; Cochlear Nerve; Electrodes, Implanted; Evoked Potentials; Female; Humans; Male; Middle Aged; Sensation; Transcranial Direct Current Stimulation; Visual Perception
PubMed: 31649289
DOI: 10.1038/s41598-019-51792-8 -
The Journal of International Medical... Dec 2021We evaluated the outcomes of resection of small acoustic neuromas using the transcanal transvestibular endoscopic approach. Two patients with a small acoustic neuroma...
We evaluated the outcomes of resection of small acoustic neuromas using the transcanal transvestibular endoscopic approach. Two patients with a small acoustic neuroma were treated using this approach. The sizes of the tumors were 11 × 6 mm and 12 × 10 mm. Both tumors were removed completely without residual tumor tissue, and damage to the facial nerve and cochlear nerve was avoided. No patients developed postoperative vertigo, aggravation of postoperative facial paralysis, severe pain, or permanent postoperative complications. The patients were followed up for 6 months, and none developed recurrence. Resection of small acoustic neuromas by the transcanal transvestibular endoscopic approach is a simple and safe technique that achieves excellent functional results.
Topics: Facial Paralysis; Humans; Neoplasm, Residual; Neuroma, Acoustic; Postoperative Complications
PubMed: 34929111
DOI: 10.1177/03000605211062445 -
Journal of Visualized Experiments : JoVE Sep 2022Deafness is the most common sensory impairment, affecting approximately 5% or 430 million people worldwide as per the World Health Organization. Aging or presbycusis is...
Deafness is the most common sensory impairment, affecting approximately 5% or 430 million people worldwide as per the World Health Organization. Aging or presbycusis is a primary cause of sensorineural hearing loss and is characterized by damage to hair cells, spiral ganglion neurons (SGNs), and the stria vascularis. These structures reside within the cochlea, which has a complex, spiral-shaped anatomy of membranous tissues suspended in fluid and surrounded by bone. These properties make it technically difficult to investigate and quantify histopathological changes. To address this need, we developed a light-sheet microscope (TSLIM) that can image and digitize the whole cochlea to facilitate the study of structure-function relationships in the inner ear. Well-aligned serial sections of the whole cochlea result in a stack of images for three-dimensional (3D) volume rendering and segmentation of individual structures for 3D visualization and quantitative analysis (i.e., length, width, surface, volume, and number). Cochleae require minimal processing steps (fixation, decalcification, dehydration, staining, and optical clearing), all of which are compatible with subsequent high-resolution imaging by scanning and transmission electron microscopy. Since all the tissues are present in the stacks, each structure can be assessed individually or relative to other structures. In addition, since imaging uses fluorescent probes, immunohistochemistry and ligand binding can be used to identify specific structures and their 3D volume or distribution within the cochlea. Here we used TSLIM to examine cochleae from aged mice to quantify the loss of hair cells and spiral ganglion neurons. In addition, advanced analyses (e.g., cluster analysis) were used to visualize local reductions of spiral ganglion neurons in Rosenthal's canal along its 3D volume. These approaches demonstrate TSLIM microscopy's ability to quantify structure-function relationships within and between cochleae.
Topics: Mice; Animals; Fluorescent Dyes; Ligands; Cochlea; Spiral Ganglion; Microscopy, Fluorescence; Aging
PubMed: 36282698
DOI: 10.3791/64420 -
The Journal of Physiology Jan 2022Understanding communication signals, especially in noisy environments, is crucial to social interactions. Yet, as we age, acoustic signals can be disrupted by cochlear...
Understanding communication signals, especially in noisy environments, is crucial to social interactions. Yet, as we age, acoustic signals can be disrupted by cochlear damage and the subsequent auditory nerve fibre degeneration. The most vulnerable medium- and high-threshold-auditory nerve fibres innervate various cell types in the cochlear nucleus, among which the small cells are unique in receiving this input exclusively. Furthermore, small cells project to medial olivocochlear (MOC) neurons, which in turn send branched collaterals back into the small cell cap. Here, we use single-unit recordings to characterise small cell firing characteristics and demonstrate superior intensity coding in this cell class. We show converse effects when activating/blocking the MOC system, demonstrating that small-cell unique coding properties are facilitated by direct cholinergic input from the MOC system. Small cells also maintain tone-level coding in the presence of background noise. Finally, small cells precisely code low-frequency modulation more accurately than other ventral cochlear nucleus cell types, demonstrating accurate envelope coding that may be important for vocalisation processing. These results highlight the small cell olivocochlear circuit as a key player in signal processing in noisy environments, which may be selectively degraded in ageing or after noise insult. KEY POINTS: Cochlear nucleus small cells receive input from low/medium spontaneous rate auditory nerve fibres and medial olivocochlear neurons. Electrical stimulation of medial olivocochlear neurons in the ventral nucleus of the trapezoid body and blocking cholinergic input to small cells using atropine demonstrates an excitatory cholinergic input to small cells, which increases responses to suprathreshold sound. Unique inputs to small cells produce superior sound intensity coding. This coding of intensity is preserved in the presence of background noise, an effect exclusive to this cell type in the cochlear nucleus. These results suggest that small cells serve an essential function in the ascending auditory system, which may be relevant to disorders such as hidden hearing loss.
Topics: Acoustic Stimulation; Cochlea; Cochlear Nerve; Cochlear Nucleus; Olivary Nucleus; Trapezoid Body
PubMed: 34761815
DOI: 10.1113/JP282262 -
The Journal of the Acoustical Society... Jan 2022One challenging issue in speaker identification (SID) is to achieve noise-robust performance. Humans can accurately identify speakers, even in noisy environments. We can...
One challenging issue in speaker identification (SID) is to achieve noise-robust performance. Humans can accurately identify speakers, even in noisy environments. We can leverage our knowledge of the function and anatomy of the human auditory pathway to design SID systems that achieve better noise-robust performance than conventional approaches. We propose a text-dependent SID system based on a real-time cochlear model called cascade of asymmetric resonators with fast-acting compression (CARFAC). We investigate the SID performance of CARFAC on signals corrupted by noise of various types and levels. We compare its performance with conventional auditory feature generators including mel-frequency cepstrum coefficients, frequency domain linear predictions, as well as another biologically inspired model called the auditory nerve model. We show that CARFAC outperforms other approaches when signals are corrupted by noise. Our results are consistent across datasets, types and levels of noise, different speaking speeds, and back-end classifiers. We show that the noise-robust SID performance of CARFAC is largely due to its nonlinear processing of auditory input signals. Presumably, the human auditory system achieves noise-robust performance via inherent nonlinearities as well.
Topics: Algorithms; Cochlea; Cochlear Nerve; Humans; Noise; Speech Perception
PubMed: 35105043
DOI: 10.1121/10.0009314 -
ELife Sep 2023Profound congenital sensorineural hearing loss (SNHL) prevents children from developing spoken language. Cochlear implantation and auditory brainstem implantation can...
Profound congenital sensorineural hearing loss (SNHL) prevents children from developing spoken language. Cochlear implantation and auditory brainstem implantation can provide partial hearing sensation, but language development outcomes can vary, particularly for patients with inner ear malformations and/or cochlear nerve deficiency (IEM&CND). Currently, the peripheral auditory structure is evaluated through visual inspection of clinical imaging, but this method is insufficient for surgical planning and prognosis. The central auditory pathway is also challenging to examine in vivo due to its delicate subcortical structures. Previous attempts to locate subcortical auditory nuclei using fMRI responses to sounds are not applicable to patients with profound hearing loss as no auditory brainstem responses can be detected in these individuals, making it impossible to capture corresponding blood oxygen signals in fMRI. In this study, we developed a new pipeline for mapping the auditory pathway using structural and diffusional MRI. We used a fixel-based approach to investigate the structural development of the auditory-language network for profound SNHL children with normal peripheral structure and those with IEM&CND under 6 years old. Our findings indicate that the language pathway is more sensitive to peripheral auditory condition than the central auditory pathway, highlighting the importance of early intervention for profound SNHL children to provide timely speech inputs. We also propose a comprehensive pre-surgical evaluation extending from the cochlea to the auditory-language network, showing significant correlations between age, gender, Cn.VIII median contrast value, and the language network with post-implant qualitative outcomes.
Topics: Humans; Child; Hearing Loss, Sensorineural; Language; Hearing; Cochlea; Cochlear Nerve
PubMed: 37697742
DOI: 10.7554/eLife.85983 -
Ear and HearingIn this study, we aimed to (1) review the long-term outcomes of cochlear implantation in children with cochlear nerve aplasia and (2) compare the development of their...
OBJECTIVES
In this study, we aimed to (1) review the long-term outcomes of cochlear implantation in children with cochlear nerve aplasia and (2) compare the development of their auditory and speech abilities to children with normal-sized cochlear nerves.
DESIGN
This is a retrospective case-control study. Patients who underwent unilateral cochlear implant (CI) surgery in a tertiary referral center from September 2012 to December 2018 were reviewed. The study group included 55 children with cochlear nerve aplasia diagnosed using preoperative images. The control group included 35 children with normal-sized cochlear nerves. The control group did not differ from the study group in terms of age at implantation, pre-implantation auditory and speech abilities, or the electrode array type. Cochlear implantation outcomes were assessed using a test battery, including the Categories of Auditory Performance (CAP) score, the Speech Intelligibility Rating (SIR) score, behavioral audiometry, and closed- or open-set speech recognition tests. The development of auditory and speech abilities was compared between the two groups using Generalized Linear Mixed-effect Models.
RESULTS
The mean duration of CI usage was 4.5 years (SD = 1.5, range = 2.0 to 9.5) in the study group. The CAP scores, SIR scores, and aided hearing thresholds improved significantly post-implantation in the study group, but were significantly poorer than those in the control group. Generalized Linear Mixed-effect Models showed that the development of CAP and SIR scores was significantly slower in the study group than in the control group. Overall, 27 (49%) children with cochlear nerve aplasia had some degree of open-set speech perception skills, but the monosyllabic and bisyllabic word recognition rates were significantly lower than those in the control group.
CONCLUSION
For children with cochlear nerve aplasia, auditory perception and speech intelligibility continued to improve in the long-term follow-up, but this progress was significantly slower than in children with normal-sized cochlear nerves. Most children with cochlear nerve aplasia could obtain the ability of common phrase perception and understanding simple spoken language with consistent CI usage and auditory rehabilitation.
Topics: Child; Humans; Infant; Cochlear Implantation; Retrospective Studies; Case-Control Studies; Hearing Tests; Cochlear Implants; Speech Perception; Speech Intelligibility; Cochlear Nerve; Treatment Outcome; Deafness
PubMed: 36476611
DOI: 10.1097/AUD.0000000000001299 -
EMBO Molecular Medicine Jun 2021Optogenetic stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in current cochlear implants. Here, we...
Optogenetic stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in current cochlear implants. Here, we employed fast and very fast variants of the red-light-activated channelrhodopsin (ChR) Chrimson (f-Chrimson and vf-Chrimson) to study their utility for optogenetic stimulation of SGNs in mice. The light requirements were higher for vf-Chrimson than for f-Chrimson, even when optimizing membrane expression of vf-Chrimson by adding potassium channel trafficking sequences. Optogenetic time and intensity coding by single putative SGNs were compared with coding of acoustic clicks. vf-Chrimson enabled putative SGNs to fire at near-physiological rates with good temporal precision up to 250 Hz of stimulation. The dynamic range of SGN spike rate coding upon optogenetic stimulation was narrower than for acoustic clicks but larger than reported for electrical stimulation. The dynamic range of spike timing, on the other hand, was more comparable for optogenetic and acoustic stimulation. In conclusion, f-Chrimson and vf-Chrimson are promising candidates for optogenetic stimulation of SGNs in auditory research and future cochlear implants.
Topics: Animals; Auditory Pathways; Channelrhodopsins; Cochlear Implants; Mice; Optogenetics; Spiral Ganglion
PubMed: 33960685
DOI: 10.15252/emmm.202013391