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Multi-pitch perception is investigated in a listening test using 30 recordings of musical sounds with two tones played simultaneously, except for two gong sounds with inharmonic overtone spectra, judging roughness and separateness as the ability to tell the two tones in each recording apart. Of the sounds, 13 were from a Western guitar playing all 13 intervals in one octave, the other sounds were mainly from non-Western instruments, comparing familiar with unfamiliar instrument sounds for Western listeners. Additionally the sounds were processed in a cochlea model, transferring the mechanical basilar membrane motion into neural spikes followed by post-processing simulating different degrees of coincidence detection. Separateness perception showed a clear distinction between familiar and unfamiliar sounds, while roughness perception did not. By correlating perception with simulation different perception strategies were found. Familiar sounds correlated strongly positively with high degrees of coincidence detection, where only 3–5 periodicities were left, while unfamiliar sounds correlated with low coincidence levels. This corresponds to an attention to pitch and timbre, respectively. Additionally, separateness perception showed an opposite correlation between perception and neural correlates between familiar and unfamiliar sounds. This correlates with the perceptional finding of the distinction between familiar and unfamiliar sounds with separateness. [ABSTRACT FROM AUTHOR]

Multiple propagation modes progress along the basilar membrane and Reissner’s membrane, called basilar membrane mode (BM mode) and Reissner’s membrane mode (RM mode), respectively. This study focuses on the effects of the RM mode on the hearing process and investigates the difference in the attenuation characteristics between the RM and BM modes in the vicinity of the cochlea base by using modal analysis. Results indicated that the RM mode has fewer effects on the hearing process, except otoacoustic emissions, due to its bigger attenuation constant than the BM mode in the vicinity of the cochlea base. The structural dependency of the attenuation constant of the RM mode is also investigated.

Active middle ear implants (AMEI) amplify mechanical vibrations in the middle ear and transmit them to the cochlea. The AMEI includes a floating mass transducer (FMT) that can be placed using two different surgical approaches: "oval window (OW) vibroplasty" and "round window (RW) vibroplasty." The OW and RW are windows located on the cochlea. Normally, sound stimulus is transmitted from the middle ear to cochlea via the OW. RW vibroplasty has been suggested as an alternative method due to the difficulty of applying OW vibroplasty in patients with ossicle dysfunction. Several reports compare the advantages of each approach through pre and postoperative hearing tests. However, quantitatively assessing the treatment effect is challenging due to individual differences in pathologies. This study investigates the vibration transmission efficiency of each surgical approach using a finite-element model of the human cochlea. Vibration of the basilar membrane (BM) of the cochlea is simulated by applying the stimulus through the OW or RW. Pathological conditions, such as impaired stapes mobility, are simulated by increasing the stiffness of the stapedial annular ligament. RW closure due to chronic middle ear diseases is a common clinical occurrence and is simulated by increasing the stiffness of the RW membrane in the model. The results show that the vibration amplitude of the BM is larger when the stimulus is applied to the RW compared to the OW, except for cases of RW membrane ossification. The difference in these amplitudes is particularly significant when stapedial mobility is limited. These results suggest that RW vibroplasty would be advantageous, especially in cases of accompanying stapedial mobility impairment. Additionally, it is suggested that transitioning to OW vibroplasty could still ensure a sufficient level of vibratory transmission efficiency when placing the FMT on the RW membrane is di cult due to anatomical problems in the tympanic cavity or confirmed severe pathological conditions around the RW. [ABSTRACT FROM AUTHOR]

A spiral‐artificial basilar membrane (S‐ABM) sensor is reported that mimics the basilar membrane (BM) of the human cochlea and can detect sound by separating it into 24 sensing channels based on the frequency band. For this, an analytical function is proposed to design the width of the BM so that the frequency bands are linearly located along the length of the BM. To fabricate the S‐ABM sensor, a spiral‐shaped polyimide film is used as a vibrating membrane, with maximum displacement at locations corresponding to specific frequency bands of sound, and attach piezoelectric sensor modules made of poly(vinylidene fluoride‐trifluoroethylene) film on top of the polyimide film to measure the vibration amplitude at each channel location. As the result, the S‐ABM sensor implements a characteristic frequency band of 96‐12,821 Hz and 24‐independent critical bands. Using real‐time signals from discriminate channels, it is demonstrated that the sensor can rapidly identify the operational noises from equipment processes as well as vehicle sounds from environmental noises on the road. The sensor can be used in a variety of applications, including speech recognition, dangerous situation recognition, hearing aids, and cochlear implants, and more. [ABSTRACT FROM AUTHOR]

In order to extract the line-spectrum features of underwater acoustic targets in complex environments, an auditory convolutional neural network (ACNN) with the ability of frequency component perception, timbre perception and critical information perception is proposed in this paper inspired by the human auditory perception mechanism. This model first uses a gammatone filter bank that mimics the cochlear basilar membrane excitation response to decompose the input time-domain signal into a number of sub-bands, which guides the network to perceive the line-spectrum frequency information of the underwater acoustic target. A sequence of convolution layers is then used to filter out interfering noise and enhance the line-spectrum components of each sub-band by simulating the process of calculating the energy distribution features, after which the improved channel attention module is connected to select line spectra that are more critical for recognition, and in this module, a new global pooling method is proposed and applied in order to better extract the intrinsic properties. Finally, the sub-band information is fused using a combination layer and a single-channel convolution layer to generate a vector with the same dimensions as the input signal at the output layer. A decision module with a Softmax classifier is added behind the auditory neural network and used to recognize the five classes of vessel targets in the ShipsEar dataset, achieving a recognition accuracy of 99.8%, which is improved by 2.7% compared to the last proposed DRACNN method, and there are different degrees of improvement over the other eight compared methods. The visualization results show that the model can significantly suppress the interfering noise intensity and selectively enhance the radiated noise line-spectrum energy of underwater acoustic targets. [ABSTRACT FROM AUTHOR]

Sound vibrations generate electrical signals called cochlear potentials, which can reflect cochlear stereocilia movement and outer hair cells (OHC) mechanical activity. However, because the cochlear structure is delicate and complex, it is difficult for existing measurement techniques to pinpoint the origin of potentials. This limitation in measurement capability makes it difficult to fully understand the contribution of stereocilia and transduction channels to cochlear potentials. In view of this, firstly, this article obtains the stereocilia movement generated by basilar membrane (BM) vibration based on the positional relationship between the various structures of the organ Corti. Secondly, Kirchhoff's law is used to establish an electric field model of the cochlear cavity, and the stereocilia movement is embedded in the electric field by combining the gated spring model. Finally, a force-electric coupling mathematical model of the cochlea is established. The results indicated that the resistance variation between different cavities in the cochlea leads to a sharp tuning curve. As the displacement of the BM increased, the longitudinal potential along the cochlea continued to move toward the base. The decrease in stereocilia stiffness reduced the deflection angle, thereby reducing the transduction current and lymphatic potential. [ABSTRACT FROM AUTHOR]

In order to improve the prediction accuracy of the sound quality of vehicle interior noise, a novel sound quality prediction model was proposed based on the physiological response predicted metrics, i.e., loudness, sharpness, and roughness. First, a human-ear sound transmission model was constructed by combining the outer and middle ear finite element model with the cochlear transmission line model. This model converted external input noise into cochlear basilar membrane response. Second, the physiological perception models of loudness, sharpness, and roughness were constructed by transforming the basilar membrane response into sound perception related to neuronal firing. Finally, taking the calculated loudness, sharpness, and roughness of the physiological model and the subjective evaluation values of vehicle interior noise as the parameters, a sound quality prediction model was constructed by TabNet model. The results demonstrate that the loudness, sharpness, and roughness computed by the human-ear physiological model exhibit a stronger correlation with the subjective evaluation of sound quality annoyance compared to traditional psychoacoustic parameters. Furthermore, the average error percentage of sound quality prediction based on the physiological model is only 3.81%, which is lower than that based on traditional psychoacoustic parameters. [ABSTRACT FROM AUTHOR]

High spatial‐resolution detection is essential for biomedical applications and human‐machine interaction. However, as the sensor array density increases, the miniaturization will lead to interference between adjacent units and deterioration in sensing performance. Here, inspired by the cochlea's sensing structure, a high‐density flexible pressure sensor array featuring with suspended sensing membrane with sensitivity‐enhanced customized channels is presented for crosstalk‐free and high‐resolution detection. By imitating the basilar membrane attached to spiral ligaments, a sensing membrane is fixed onto a high‐stiffness substrate with cavities, forming a stable braced isolation to provide an excellent crosstalk‐free capability (crosstalk coefficient: 47.24 dB) with high‐density integration (100 units within 1 cm2). Similar to the opening of ion channels in hair cells, the wedge‐type expansion of the embedded cracks introduced by stress concentration structures enables a high sensitivity (0.19 kPa−1) and a large measuring range (400 kPa). Finally, it demonstrates promising applications in distributed displays and the condition monitoring of medical‐surgical intubation. [ABSTRACT FROM AUTHOR]

Background: Various representations exist in the literature to visualize electrocochleography (ECochG) recordings along the basilar membrane (BM). This lack of generalization complicates comparisons within and between cochlear implant (CI) users, as well as between publications. This study synthesized the visual representations available in the literature via a systematic review and provides a novel approach to visualize ECochG data in CI users. Methods: A systematic review was conducted within PubMed and EMBASE to evaluate studies investigating ECochG and CI. Figures that visualized ECochG responses were selected and analyzed. A novel visualization of individual ECochG data, the ZH-ECochG Bode plot (ZH = Zurich), was devised, and the recordings from three CI recipients were used to demonstrate and assess the new framework. Results: Within the database search, 74 articles with a total of 115 figures met the inclusion criteria. Analysis revealed various types of representations using different axes; their advantages were incorporated into the novel visualization framework. The ZH-ECochG Bode plot visualizes the amplitude and phase of the ECochG recordings along the different tonotopic regions and angular insertion depths of the recording sites. The graph includes the pre- and postoperative audiograms to enable a comparison of ECochG responses with the audiometric profile, and allows different measurements to be shown in the same graph. Conclusions: The ZH-ECochG Bode plot provides a generalized visual representation of ECochG data, using well-defined axes. This will facilitate the investigation of the complex ECochG potentials generated along the BM and allows for better comparisons of ECochG recordings within and among CI users and publications. The scripts used to construct the ZH-ECochG Bode plot are provided by the authors. [ABSTRACT FROM AUTHOR]

Background: Despite its location near infection-prone areas, the human inner ear demonstrates remarkable resilience. This suggests that there are inherent instruments deterring the invasion and spread of pathogens into the inner ear. Here, we combined high-resolution light microscopy, super-resolution immunohistochemistry (SR-SIM) and synchrotron phase contrast imaging (SRPCI) to identify the protection and barrier systems in the various parts of the human inner ear, focusing on the lateral wall, spiral ganglion, and endolymphatic sac. Materials and methods: Light microscopy was conducted on mid-modiolar, semi-thin sections, after direct glutaraldehyde/osmium tetroxide fixation. The tonotopic locations were estimated using SR-PCI and 3D reconstruction in cadaveric specimens. The sections were analyzed for leucocyte and macrophage activity, and the results were correlated with immunohistochemistry using confocal microscopy and SR-SIM. Results: Light microscopy revealed unprecedented preservation of cell anatomy and several macrophage-like cells that were localized in the cochlea. Immunohistochemistry demonstrated IBA1 cells frequently co-expressing MHC II in the spiral ganglion, nerve fibers, lateral wall, spiral limbus, and tympanic covering layer at all cochlear turns as well as in the endolymphatic sac. RNAscope assays revealed extensive expression of fractalkine gene transcripts in type I spiral ganglion cells. CD4 and CD8 cells occasionally surrounded blood vessels in the modiolus and lateral wall. TMEM119 and P2Y12 were not expressed, indicating that the cells labeled with IBA1 were not microglia. The round window niche, compact basilar membrane, and secondary spiral lamina may form protective shields in the cochlear base. Discussion: The results suggest that the human cochlea is surveilled by dwelling and circulating immune cells. Resident and blood-borne macrophages may initiate protective immune responses via chemokine signaling in the lateral wall, spiral lamina, and spiral ganglion at different frequency locations. Synchrotron imaging revealed intriguing protective barriers in the base of the cochlea. The role of the endolymphatic sac in human inner ear innate and adaptive immunity is discussed. [ABSTRACT FROM AUTHOR]

Pending questions regarding cochlear amplification and tuning are hinged upon the organ of Corti (OoC) active mechanics: how outer hair cells modulate OoC vibrations. Our knowledge regarding OoC mechanics has advanced over the past decade thanks to the application of tomographic vibrometry. However, recent data from live cochlea experiments often led to diverging interpretations due to complicated interaction between passive and active responses, lack of image resolution in vibrometry, and ambiguous measurement angles. We present motion measurements and analyses of the OoC sub-components at the close-to-true cross-section, measured from acutely excised gerbil cochleae. Specifically, we focused on the vibrating patterns of the reticular lamina, the outer pillar cell, and the basilar membrane because they form a structural frame encasing active outer hair cells. For passive transmission, the OoC frame serves as a rigid truss. In contrast, motile outer hair cells exploit their frame structures to deflect the upper compartment of the OoC while minimally disturbing its bottom side (basilar membrane). Such asymmetric OoC vibrations due to outer hair cell motility explain how recent observations deviate from the classical cochlear amplification theory. We analyzed the organ of Corti motions, component by component. Outer hair cells exploit their supporting cells to boost vibrations of the upper part of the organ of Corti while minimally disturbing the basilar membrane. [ABSTRACT FROM AUTHOR]

In recent years, tools for early detection of irreversible trauma to the basilar membrane during hearing preservation cochlear implant (CI) surgery were established in several clinics. A link with the degree of postoperative hearing preservation in patients was investigated, but patient populations were usually small. Therefore, this study's aim was to analyze data from intraoperative extracochlear electrocochleography (ECochG) recordings for a larger group. During hearing preservation CI surgery, extracochlear recordings were made before, during, and after CI electrode insertion using a cotton wick electrode placed at the promontory. Before and after insertion, amplitudes and stimulus response thresholds were recorded at 250, 500, and 1000 Hz. During insertion, response amplitudes were recorded at one frequency and one stimulus level. Data from 121 patient ears were analyzed. The key benefit of extracochlear recordings is that they can be performed before, during, and after CI electrode insertion. However, extracochlear ECochG threshold changes before and after CI insertion were relatively small and did not independently correlate well with hearing preservation, although at 250 Hz they added some significant information. Some tendencies—although no significant relationships—were detected between amplitude behavior and hearing preservation. Rising amplitudes seem favorable and falling amplitudes disadvantageous, but constant amplitudes do not appear to allow stringent predictions. Extracochlear ECochG measurements seem to only partially realize expected benefits. The questions now are: do gains justify the effort, and do other procedures or possible combinations lead to greater benefits for patients? [ABSTRACT FROM AUTHOR]

Commercially available cochlear implants are designed to aid profoundly deaf people in understanding speech and environmental sounds. A typical cochlear implant uses a bank of bandpass filters to decompose an audio signal into a set of dynamic signals. These filters' critical center frequencies f 0 imitate the human cochlea's vibration patterns caused by audio signals. Gammatone filters (GTFs), with two unique characteristics: (a) an appropriate "pseudo resonant" frequency transfer function, mimicking the human cochlea, and (b) realizing efficient hardware implementation, could demonstrate them as unique candidates for cochlear implant design. Although GTFs have recently attracted considerable attention from researchers, a comprehensive exposition of GTFs is still absent in the literature. This paper starts by enumerating the impulse response of GTFs. Then, the magnitude spectrum, | H (f) | , and bandwidth, more specifically, the equivalent rectangular bandwidth (ERB) of GTFs, are derived. The simulation results suggested that optimally chosen filter parameters, e.g., critical center frequencies, f 0 ; temporal decay parameter, b ; and order of the filter, n , can minimize the interference of the filter bank frequencies and very likely model the filter bandwidth (ERB), independent of f 0 b . Finally, these optimized filters are applied to delineate a filter bank for a cochlear implant design based on the Clarion processor model. [ABSTRACT FROM AUTHOR]

Mammalian auditory hair cells transduce sound-evoked traveling waves in the cochlea into nerve stimuli, which are essential for hearing function. Pillar cells located between the inner and outer hair cells are involved in the formation of the tunnel of Corti, which incorporates outer-hair-cell-driven fluid oscillation and basilar membrane movement, leading to the fine-tuned frequency-specific perception of sounds by the inner hair cells. However, the detailed molecular mechanism underlying the development and maintenance of pillar cells remains to be elucidated. In this study, we examined the expression and function of brain-specific angiogenesis inhibitor 3 (Bai3), an adhesion G-protein-coupled receptor, in the cochlea. We found that Bai3 was expressed in hair cells in neonatal mice and pillar cells in adult mice, and, interestingly, Bai3 knockout mice revealed the abnormal formation of pillar cells, with the elevation of the hearing threshold in a frequency-dependent manner. Furthermore, old Bai3 knockout mice showed the degeneration of hair cells and spiral ganglion neurons in the basal turn. The results suggest that Bai3 plays a crucial role in the development and/or maintenance of pillar cells, which, in turn, are necessary for normal hearing function. Our results may contribute to understanding the mechanisms of hearing loss in human patients. [ABSTRACT FROM AUTHOR]

Tinnitus is the perception of noise in the absence of acoustic stimulation (phantom noise). In most patients suffering from chronic peripheral tinnitus, an alteration of outer hair cells (OHC) starting from the stereocilia (SC) occurs. This is common following ototoxic drugs, sound-induced ototoxicity, and acoustic degeneration. In all these conditions, altered coupling between the tectorial membrane (TM) and OHC SC is described. The present review analyzes the complex interactions involving OHC and TM. These need to be clarified to understand which mechanisms may underlie the onset of tinnitus and why the neuropathology of chronic degenerative tinnitus is similar, independent of early triggers. In fact, the fine neuropathology of tinnitus features altered mechanisms of mechanic-electrical transduction (MET) at the level of OHC SC. The appropriate coupling between OHC SC and TM strongly depends on autophagy. The involvement of autophagy may encompass degenerative and genetic tinnitus, as well as ototoxic drugs and acoustic trauma. Defective autophagy explains mitochondrial alterations and altered protein handling within OHC and TM. This is relevant for developing novel treatments that stimulate autophagy without carrying the burden of severe side effects. Specific phytochemicals, such as curcumin and berberin, acting as autophagy activators, may mitigate the neuropathology of tinnitus. [ABSTRACT FROM AUTHOR]

In this study, we explore nonlinear cochlear amplification by analyzing basilar membrane (BM) motion in the mouse apex. Through in vivo, postmortem, and mechanical suppression recordings, we estimate how the cochlear amplifier nonlinearly shapes the wavenumber of the BM traveling wave, specifically within a frequency range where the short-wave approximation holds. Our findings demonstrate that a straightforward mathematical model, depicting the cochlear amplifier as a wavenumber modifier with strength diminishing monotonically as BM displacement increases, effectively accounts for the various experimental observations. This empirically derived model is subsequently incorporated into a physics-based "overturned" framework of cochlear amplification [see Altoè, Dewey, Charaziak, Oghalai, and Shera (2022), J. Acoust. Soc. Am. 152, 2227–2239] and tested against additional experimental data. Our results demonstrate that the relationships established within the short-wave region remain valid over a much broader frequency range. Furthermore, the model, now exclusively calibrated to BM data, predicts the behavior of the opposing side of the cochlear partition, aligning well with recent experimental observations. The success in reproducing key features of the experimental data and the mathematical simplicity of the resulting model provide strong support for the "overturned" theory of cochlear amplification. [ABSTRACT FROM AUTHOR]

Hearing evolved in lampreys with a frequency range of 50–200 Hz. This hearing range is comparable to that of elasmobranchs, most non-teleosts, and lungfish. Elasmobranchs most likely use the saccule and the papilla neglecta (PN) for hearing. In non-teleosts and teleosts, lungfish, and certain tetrapods the saccule is the likely sensor for sound reception while the lagena and the PN are important for gravistatic sensing. Coelacanth and most tetrapods have a basilar papilla (BP) for hearing. In coelacanth and tetrapods, the hair cells of the BP are in contact with a basilar and a tectorial membrane. These membranes transmit mechanical vibrations. A cochlear aqueduct (CA) provides a connection between the cerebrospinal fluid that has a sodium rich space in coelacanth and tetrapods while the potassium rich endolymph is known in vertebrates. A unique feature is known in basic sarcopterygians, the intracranial joint, that never developed in actinopterygians and has been lost in lungfish and tetrapods. The BP in coelacanths is thought to generate pressure with the intracranial joint that will be transmitted to the CA. Lungs or a swim bladder are not forming in Chondrichthyes, structures that have a major impact on hearing in teleosts and tetrapods. [ABSTRACT FROM AUTHOR]

Cochlear implantation (CI) allows rehabilitation for patients with severe to profound hearing impairment. Although the use of a robotic assistant provides technical assistance to the surgeon, the assessment of the impact of its use on auditory outcomes remains uncertain. We aim to compare the hearing results of patients who underwent bilateral cochlear implantation; one side was performed with manual insertion and the other side with robot-assisted insertion. The electrode array intrascalar positioning and the surgery duration were also studied. This retrospective intra-individual study involved 10 patients who underwent bilateral cochlear implantation. The study included two infants and eight adults. The unique composition of this cohort enabled us to utilize each patient as their own control. Regarding speech disyllabic recognition, pure tone average, ECAP, ratio of array translocation, basilar membrane rupture, and percentage of translocated electrodes, there was no difference between manual and robot-assisted CI groups. This study is the first to compare intra-individual hearing performance after cochlear implantation, either manually or robot-assisted. The number of patients and the time delay between manual and robotic implantation may have led to a lack of power, but there was no apparent difference in hearing performance between manual and robotic implantation. [ABSTRACT FROM AUTHOR]

The intricate, crystalline cytoarchitecture of the mammalian organ of Corti presumably plays an important role in cochlear amplification. As currently understood, the oblique, Y-shaped arrangement of the outer hair cells (OHCs) and phalangeal processes of the Deiters cells serves to create differential “push–pull” forces that drive the motion of the basilar membrane via the spatial feedforward and/or feedbackward of OHC forces. In concert with the cochlear traveling wave, the longitudinal separation between OHC sensing and forcing creates phase shifts that yield a form of negative damping, amplifying waves as they propagate. Unlike active forces that arise and act locally, push– pull forces are inherently directional—whereas forward-traveling waves are boosted, reverse-traveling waves are squelched. Despite their attractions, models based on push– pull amplification must contend with otoacoustic emissions (OAEs), whose existence implies that amplified energy escapes from the inner ear via mechanisms involving reverse traveling waves. We analyze hybrid local/push–pull models to determine the constraints that reflection-source OAEs place on the directionality of cochlear wave propagation. By implementing a special force-mixing control knob, we vary the mix of local and push–pull forces while leaving the forward-traveling wave unchanged. Consistency with stimulus-frequency OAEs requires that the active forces underlying cochlear wave amplification be primarily local in character, contradicting the prevailing view. By requiring that the oblique cytoarchitecture produce predominantly local forces, we reinterpret the functional role of the Y-shaped geometry, proposing that it serves not as a push–pull amplifier, but as a mechanical funnel that spatially integrates local OHC forces. [ABSTRACT FROM AUTHOR]

There are several pathologies that can change the anatomy of the otic capsule and that can distort the bone density of the bony structures of the inner ear, but otosclerosis is one of the most frequent. Similar behavior has been shown in patients affected by osteogenesis imperfecta (OI), a genetic disorder due to a mutation in the genes coding for type I (pro) collagen. In particular, we note that otosclerosis and OI can lead to bone resorption creating pericochlear cavitations in contact with the internal auditory canal (IAC). In this regard, we have collected five cases presenting this characteristic; their audiological data and clinical history were analyzed. This feature can be defined as a potential cause of a third-window effect, because it causes an energy loss during the transmission of sound waves from the oval window (OW) away from the basilar membrane. [ABSTRACT FROM AUTHOR]

As of today, image-based assessment of cochlear implant electrode array location is not part of the clinical routine. Low resolution and contrast of computer tomography (CT) imaging, as well as electrode array artefacts, prevent visibility of intracochlear structures and result in low accuracy in determining location of the electrode array. Further, trauma assessment based on clinical-CT images requires a uniform image-based trauma scaling. Goal of this study was to evaluate the accuracy of a novel imaging software to detect electrode scalar location. Six cadaveric temporal bones were implanted with Advanced Bionics SlimJ and Mid-Scala electrode arrays. Clinical-CT scans were taken pre- and postoperatively. In addition, micro-CTs were taken post-operatively for validation. The electrode scalar location rating done by the software was compared to the rating of two experienced otosurgeons and the micro-CT images. A 3-step electrode scalar location grading scale (0 = electrode in scala tympani, 1 = interaction of electrode with basilar membrane/osseous spiral lamina, 2 = translocation of electrode into scala vestibuli) was introduced for the assessment. The software showed a high sensitivity of 100% and a specificity of 98.7% for rating the electrode location. The correlation between rating methods was strong (kappa > 0.890). The software gives a fast and reliable method of evaluating electrode scalar location for cone beam CT scans. The introduced electrode location grading scale was adapted for assessing clinical CT images. [ABSTRACT FROM AUTHOR]

Musculocontractural Ehlers–Danlos syndrome (EDS) caused by pathogenic variants in CHST14 (mcEDS-CHST14) is a subtype of EDS characterized by multisystem malformations and progressive fragility-related manifestations. A recent international collaborative study showed that 55% of mcEDS-CHST14 patients had hearing loss (HL), more commonly of the high-frequency type. Here, we report the first systemic investigation of the otological features of patients with this disorder based on the world's largest cohort at Shinshu University Hospital. Nine patients [18 ears; four male and five female patients; mean age, 18 years old (range, 10–28)] underwent comprehensive otological evaluation: audiogram, distortion product otoacoustic emission (DPOAE) test, and tympanometry. The audiogram, available in all 18 ears, showed HL in eight patients (8/9, 89%) and in 14 ears (14/18, 78%): bilateral in six patients (6/9, 67%) and unilateral in two (2/9, 22%); mild in eight ears (8/18, 44%) and moderate in six (6/18, 33%); and high-frequency HL in five (5/18, 28%) and low-frequency HL in five (5/18, 28%). An air-bone gap was detected in one ear (1/18, 6%). DPOAE was available in 13 ears, with the presence of a response in five (5/13, 38%) and the absence in eight (8/13, 62%), including in three ears of normal hearing. Tympanometry results were available in 12 ears: Ad type in nine (9/12, 75%) and As type in one (1/12, 8.3%). Patients with mcEDS-CHST14 had a high prevalence of HL, typically sensorineural and bilateral, with mild to moderate severity, of high-frequency or low-frequency type, and sometimes with no DPOAE response. The pathophysiology underlying HL might be complex, presumably related to alterations of the tectorial membrane and/or the basilar membrane of Corti associated with disorganized collagen fibril networks. Regular and careful check-ups of hearing using multiple modalities are recommended for mcEDS-CHST14 patients. [ABSTRACT FROM AUTHOR]

The human auditory system is designed to capture and encode sounds from our surroundings and conspecifics. However, the precise mechanisms by which it adaptively extracts the most important spectro-temporal information from sounds are still not fully understood. Previous auditory models have explained sound encoding at the cochlear level using static filter banks, but this vision is incompatible with the nonlinear and adaptive properties of the auditory system. Here we propose an approach that considers the cochlear processes as envelope interpolations inspired by cochlear physiology. It unifies linear and nonlinear adaptive behaviors into a single comprehensive framework that provides a data-driven understanding of auditory coding. It allows simulating a broad range of psychophysical phenomena from virtual pitches and combination tones to consonance and dissonance of harmonic sounds. It further predicts the properties of the cochlear filters such as frequency selectivity. Here we propose a possible link between the parameters of the model and the density of hair cells on the basilar membrane. Cascaded Envelope Interpolation may lead to improvements in sound processing for hearing aids by providing a non-linear, data-driven, way to preprocessing of acoustic signals consistent with peripheral processes. Cascaded envelope interpolation offers a unifying framework to further understand the adaptive and nonlinear processes of auditory coding, with future implications in development of devices like hearing aids. [ABSTRACT FROM AUTHOR]

Introduction: Electrode length selection based on case-related cochlear parameters is becoming a standard pre-operative step for cochlear implantation. The manual measurement of the parameters is often time-consuming and may lead to inconsistencies. Our work aimed to evaluate a novel, automatic measurement method. Materials and Methods: A retrospective evaluation of pre-operative HRCT images of 109 ears (56 patients) was conducted, using a development version of the OTOPLAN® software. Inter-rater (intraclass) reliability and execution time were assessed for manual (surgeons R1 and R2) vs. automatic (AUTO) results. The analysis included A-Value (Diameter), B-Value (Width), H-Value (Height), and CDLOC-length (Cochlear Duct Length at Organ of Corti/Basilar membrane). Results: The measurement time was reduced from approximately 7 min ± 2 (min) (manual) to 1 min (AUTO). Cochlear parameters in mm (mean ± SD) for R1, R2 and AUTO, respectively, were A-value: 9.00 ± 0.40, 8.98 ± 0.40 and 9.16 ± 0.36; B-value: 6.81 ± 0.34, 6.71 ± 0.35 and 6.70 ± 0.40; H-value: 3.98 ± 0.25, 3.85 ± 0.25 and 3.76 ± 0.22; and the mean CDLoc-length: 35.64 ± 1.70, 35.20 ± 1.71 and 35.47 ± 1.87. AUTO CDLOC measurements were not significantly different compared to R1 and R2 (H0: Rx CDLOC = AUTO CDLOC: p = 0.831, p = 0.242, respectively), and the calculated intraclass correlation coefficient (ICC) for CDLOC was 0.9 (95% CI: 0.85, 0.932) for R1 vs. AUTO; 0.90 (95% CI: 0.85, 0.932) for R2 vs. AUTO; and 0.893 (95% CI: 0.809, 0.935) for R1 vs. R2. Conclusions: We observed excellent inter-rater reliability, a high agreement of outcomes, and reduced execution time using the AUTO method. [ABSTRACT FROM AUTHOR]

Explaining the mechanism of the cochlear active phonosensitive amplification has been a major problem in medicine. The basilar membrane (BM) is the key infrastructure. In 1960, Nobel Laureate von Békésy first discovered BM's traveling wave motion. Since that time, BM's models only have considered the traveling wave but not the biological activity. Therefore, a new model considering changes of BM's stiffness in space and time is established based on the immersed boundary method to describe its biological activity. It not only reproduces the results of traveling wave motion but also explains the mechanization on the generation of traveling wave. An important discovery is that changes of BM's stiffness in space and time will cause the unstable global resonance, which will induce amplification of sounds in cochlea. An important inference is that biological activity shall be included in the application of mechanical principles to the analysis of life, which is the essential difference between biomechanics and general mechanics. [ABSTRACT FROM AUTHOR]

Cochlear mechanics tends to be studied using single-location measurements of intracochlear vibrations in response to acoustical stimuli. Such measurements, due to their invasiveness and often the instability of the animal preparation, are difficult to accomplish and, thus, ideally require stimulus paradigms that are time efficient, flexible, and result in high resolution transfer functions. Here, a swept-sine method is adapted for recordings of basilar membrane impulse responses in mice. The frequency of the stimulus was exponentially swept from low to high (upward) or high to low (downward) at varying rates (from slow to fast) and intensities. The cochlear response to the swept-sine was then convolved with the time-reversed stimulus waveform to obtain first and higher order impulse responses. Slow sweeps of either direction produce cochlear first to third order transfer functions equivalent to those measured with pure tones. Fast upward sweeps, on the other hand, generate impulse responses that typically ring longer, as observed in responses obtained using clicks. The ringing of impulse response in mice was of relatively small amplitude and did not affect the magnitude spectra. It is concluded that swept-sine methods offer flexible and time-efficient alternatives to other approaches for recording cochlear impulse responses. [ABSTRACT FROM AUTHOR]

Purpose: A probe that binds to unfixed collagen fibrils was used to image the shapes and fibrous properties of the TM and BM. The probe (CNA35) is derived from the bacterial adhesion protein CNA. We present confocal images of hydrated gerbil TM, BM, and other cochlear structures stained with fluorescently labeled CNA35. A primary purpose of this article is to describe the use of the CNA35 collagen probe in the cochlea. Methods: Recombinant poly-histidine-tagged CNA35 was expressed in Escherichia coli, purified by cobalt-affinity chromatography, fluorescence labeled, and further purified by gel filtration chromatography. Cochleae from freshly harvested gerbil bullae were irrigated with and then incubated in CNA35 for periods ranging from 2 h — overnight. The cochleae were fixed, decalcified, and dissected. Isolated cochlear turns were imaged by confocal microscopy. Results: The CNA35 probe stained the BM and TM, and volumetric imaging revealed the shape of these structures and the collagen fibrils within them. The limbal zone of the TM stained intensely. In samples from the cochlear base, intense staining was detected on the side of the TM that faces hair cells. In the BM pectinate zone, staining was intense at the upper and lower boundaries. The BM arcuate zone was characterized by a prominent longitudinal collagenous structure. The spiral ligament, limbus and lamina stained for collagen, and within the spiral limbus the habenula perforata were outlined with intense staining. Conclusion: The CNA35 probe provides a unique and useful view of collagenous structures in the cochlea. [ABSTRACT FROM AUTHOR]

Commercially available cochlear implants are designed to aid profoundly deaf people in understanding speech and environmental sounds. A typical cochlear implant uses a bank of bandpass filters to decompose an audio signal into a set of dynamic signals. These filters’ critical center frequencies f0 imitate the human cochlea’s vibration patterns caused by audio signals. Gammatone filters (GTFs), with two unique characteristics: (a) an appropriate “pseudo resonant” frequency transfer function, mimicking the human cochlea, and (b) realizing efficient hardware implementation, could demonstrate them as unique candidates for cochlear implant design. Although GTFs have recently attracted considerable attention from researchers, a comprehensive exposition of GTFs is still absent in the literature. This paper starts by enumerating the impulse response of GTFs. Then, the magnitude spectrum, |H(f)|, and bandwidth, more specifically, the equivalent rectangular bandwidth (ERB) of GTFs, are derived. The simulation results suggested that optimally chosen filter parameters, e.g., critical center frequencies,f0; temporal decay parameter, b; and order of the filter, n, can minimize the interference of the filter bank frequencies and very likely model the filter bandwidth (ERB), independent of f0b. Finally, these optimized filters are applied to delineate a filter bank for a cochlear implant design based on the Clarion processor model.

This article, published in the Journal of the Acoustical Society of America, explores the relationship between head size and high frequency hearing in mammals. The authors conducted a study using audiograms from various species and found that smaller heads were associated with higher frequency hearing. They also observed that hearing above 32 kHz was uniquely mammalian. The findings suggest that the ability to localize sounds is important for survival and may have driven the evolution of mammalian ear specializations. The article also discusses the relationship between sound localization and visual acuity. [Extracted from the article]

Age-related hearing loss (ARHL) is the most common sensory degenerative disease and can significantly impact the quality of life in elderly people. A previous study using GeneChip miRNA microarray assays showed that the expression of miR-29a changes with age, however, its role in hearing loss is still unclear. In this study, we characterized the cochlear phenotype of miR-29a knockout (miR-29a–/–) mice and found that miR-29a-deficient mice had a rapid progressive elevation of the hearing threshold from 2 to 5 months of age compared with littermate controls as measured by the auditory brainstem response. Stereocilia degeneration, hair cell loss and abnormal stria vascularis (SV) were observed in miR-29a–/– mice at 4 months of age. Transcriptome sequencing results showed elevated extracellular matrix (ECM) gene expression in miR-29a–/– mice. Both Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the key differences were closely related to ECM. Further examination with a transmission electron microscope showed thickening of the basilar membrane in the cochlea of miR-29a–/– mice. Five Col4a genes (Col4a1-a5) and two laminin genes (Lamb2 and Lamc1) were validated as miR-29a direct targets by dual luciferase assays and miR-29a inhibition assays with a miR-29a inhibitor. Consistent with the target gene validation results, the expression of these genes was significantly increased in the cochlea of miR-29a–/– mice, as shown by RT-PCR and Western blot. These findings suggest that miR-29a plays an important role in maintaining cochlear structure and function by regulating the expression of collagen and laminin and that the disturbance of its expression could be a cause of progressive hearing loss.

Due to ethical issues and the nature of the ear, it is difficult to directly perform experimental measurements on living body elements of the human ear. Therefore, a numerical model has been developed to effectively assess the effect of the replacement of artificial ossicles on hearing in the inner ear. A healthy volunteer's right ear was scanned to obtain CT data, which were digitalized through the use of a self-compiling program and coalescent Patran-Nastran software to establish a 3D numerical model of the whole ear, and a frequency response of a healthy human ear was analyzed. The vibration characteristics of the basilar membrane (BM) after total ossicular replacement prosthesis (TORP) implantation were then analyzed. The results show that although the sound conduction function of the middle ear was restored after replacement of the TORP, the sensory sound function of the inner ear was affected. In the low frequency and medium frequency range, hearing loss was 5.2~10.7%. Meanwhile, in the middle–high frequency range, the replacement of a middle ear TORP in response to high sound pressure produced a high acoustic stimulation effect in the inner ear, making the inner ear structures susceptible to fatigue and more prone to fatigue damage compared to the structures in healthy individuals. This developed model is able to assess the effects of surgical operation on the entire hearing system. [ABSTRACT FROM AUTHOR]

The cochlea, to function efficiently towards hearing, the oxygenated blood supply is a very essential component. Yoga, a practice that originated in ancient India, claims to facilitate physical, mental, and spiritual well-being. Sudarshan Kriya Yoga (SKY) is one such practice that focuses on breathing, therefore, regulating the oxygen circulation in our body. The benefits on practicing SKY have been reported to increase oxygenated blood supply to the respective cells or tissues. DPIO is a measure of cochlear growth function that reflects the basilar membrane function and is sensitive to even a small alteration in the amount of function. Therefore, to analyze if there is an increase in the hair cell function, we compare it between the SKY practitioners and a control group of 70 middle-aged adults (40-65 years old; 35 subjects in each group) who have their hearing sensitivity within normal limits through DPIO measure. Student 't' test was used to compare the mean difference between the two groups. The results revealed that there is a significant difference between both groups with respect to the DPIO amplitude (p-value ≤ 0.05). The study concludes enhanced amplitude on DPIO measure among individuals who practice SKY when compared to non- practitioners of SKY. [ABSTRACT FROM AUTHOR]

Recent observations of sound-evoked vibrations of the cochlea's sensory organ of Corti (ooC) using optical coherence tomography (OCT) have revealed unanticipated and complex motions. Interpreting these results in terms of the micromechanical inner-ear processes that precede hair-cell transduction is not trivial since OCT only measures a projection of the true motion, which may include transverse and longitudinal displacements. We measure ooC motions at multiple OCT beam angles relative to the longitudinal axis of the basilar membrane (BM) by using the cochlea's natural curvature and find that the relative phase between outer hair cells (OHC) and BM varies with this angle. This includes a relatively abrupt phase reversal where OHC lead (lag) the BM by ~0.25 cycles for negative (positive) beam angles, respectively. We interpret these results as evidence for significant longitudinal motion within the ooC, which should be considered when interpreting (relative) ooC vibrations in terms of inner-ear sound processing. Multi-angle optical coherence tomography measurements link organ of Corti vibrations to complex motions in inner-ear sound processing. [ABSTRACT FROM AUTHOR]

In cochlear implant surgery, insertion of perimodiolar electrode arrays into the scala tympani can be complicated by trauma or even accidental translocation of the electrode array within the cochlea. In patients with partial hearing loss, cochlear trauma can not only negatively affect implant performance, but also reduce residual hearing function. These events have been related to suboptimal positioning of the cochlear implant electrode array with respect to critical cochlear walls of the scala tympani (modiolar wall, osseous spiral lamina and basilar membrane). Currently, the position of the electrode array in relation to these walls cannot be assessed during the insertion and the surgeon depends on tactile feedback, which is unreliable and often comes too late. This study presents an image-guided cochlear implant device with an integrated, fiber-optic imaging probe that provides real-time feedback using optical coherence tomography during insertion into the human cochlea. This novel device enables the surgeon to accurately detect and identify the cochlear walls ahead and to adjust the insertion trajectory, avoiding collision and trauma. The functionality of this prototype has been demonstrated in a series of insertion experiments, conducted by experienced cochlear implant surgeons on fresh-frozen human cadaveric cochleae. [ABSTRACT FROM AUTHOR]

Within the cochlea, the basilar membrane (BM) is coupled to the reticular lamina (RL) through three rows of piezo-like outer hair cells (OHCs) and supporting cells that endow mammals with sensitive hearing. Anatomical differences across OHC rows suggest differences in their motion. Using optical coherence tomography, we measured in vivo and postmortem displacements through the gerbil round-window membrane from approximately the 40–47 kHz best-frequency (BF) regions. Our high spatial resolution allowed measurements across the RL surface at the tops of the three rows of individual OHCs and their bottoms, and across the BM. RL motion varied radially; the third-row gain was more than 3 times greater than that of the first row near BF, whereas the OHC-bottom motions remained similar. This implies that the RL mosaic, comprised of OHC and phalangeal-process tops joined together by adhesion molecules, is much more flexible than the Deiters' cells connected to the OHCs at their bottom surfaces. Postmortem, the measured points moved together approximately in phase. These imply that in vivo, the RL does not move as a stiff plate hinging around the pillar-cell heads near the first row as has been assumed, but that its mosaic-like structure may instead bend and/or stretch. [ABSTRACT FROM AUTHOR]

The outer hair cells in the mammalian cochlea are cellular actuators essential for sensitive hearing. The geometry and stiffness of the structural scaffold surrounding the outer hair cells will determine how the active cells shape mammalian hearing by modulating the organ of Corti (OoC) vibrations. Specifically, the tectorial membrane and the Deiters cell are mechanically in series with the hair bundle and soma, respectively, of the outer hair cell. Their mechanical properties and anatomic arrangement must determine the relative motion among different OoC structures. We measured the OoC mechanics in the cochleas acutely excised from young gerbils of both sexes at a resolution fine enough to distinguish the displacement of individual cells. A three-dimensional finite element model of fully deformable OoC was exploited to analyze the measured data in detail. As a means to verify the computer model, the basilar membrane deformations because of static and dynamic stimulations were measured and simulated. Two stiffness ratios have been identified that are critical to understand cochlear physics, which are the stiffness of the tectorial membrane with respect to the hair bundle and the stiffness of the Deiters cell with respect to the outer hair cell body. Our measurements suggest that the Deiters cells act like a mechanical equalizer so that the outer hair cells are constrained neither too rigidly nor too weakly. [ABSTRACT FROM AUTHOR]

For evoked otoacoustic emissions (OAEs), the stimulus and emission signals traverse the middle ear (ME) in forward and reverse directions, respectively. In this study, a fully coupled three-dimensional finite-element model of the mouse ear canal (EC), ME, and cochlea was used to calculate ME pressure gains, impedances, and reflectances at the EC-entrance and stapes-footplate–cochlear-fluid interfaces. The cochlear model incorporates a series of interdigitated Y-shaped structures sandwiched between the basilar membrane and reticular lamina, each comprised of a Deiters' cell, its phalangeal-process extension, and an outer hair cell (OHC). By introducing random perturbations to the OHC gains, stimulation-frequency otoacoustic emissions (SFOAEs) were generated. Raising the perturbation magnitude from 10% to 80% increased the SFOAE magnitude by up to 24 dB in the 10–30 kHz frequency range. Increasing or decreasing the stiffness of the stapes annular ligament and eardrum by a factor of 8 changed the SFOAEs by up to 30 dB, but the round-trip ME gain as measured could not account for this. A modified round-trip ME gain, with reflections removed at the EC-entrance and stapes–cochlea boundaries, eliminated a ±10 dB discrepancy and allowed ME changes to be quantitatively associated with changes in measured OAEs. [ABSTRACT FROM AUTHOR]

The mammalian cochlea contains three rows of outer hair cells (OHCs) that amplify the basilar membrane traveling wave with high gain and exquisite tuning. The pattern of OHC loss caused by typical methods of producing hearing loss in animal models (noise, ototoxic exposure, or aging) is variable and not consistent along the length of the cochlea. Thus, it is difficult to use these approaches to understand how forces from multiple OHCs summate to create normal cochlear amplification. Here, we selectively removed the third row of OHCs and Deiters' cells in adult mice and measured cochlear amplification. In the mature cochlear epithelia, expression of the Wnt target gene Lgr5 is restricted to the third row of Deiters' cells, the supporting cells directly underneath the OHCs. Diphtheria toxin administration to Lgr5DTR-EGFP/+ mice selectively ablated the third row of Deiters' cells and the third row of OHCs. Basilar membrane vibration in vivo demonstrated disproportionately lower reduction in cochlear amplification by about 13.5 dB. On a linear scale, this means that the 33% reduction in OHC number led to a 79% reduction in gain. Thus, these experimental data describe the impact of reducing the force of cochlear amplification by a specific amount. Furthermore, these data argue that because OHC forces progressively and sequentially amplify the traveling wave as it travels to its peak, the loss of even a relatively small number of OHCs, when evenly distributed longitudinally, will cause a substantial reduction in cochlear amplification. [ABSTRACT FROM AUTHOR]

Background: The inner ear morphology and size are linked to hearing and balance ability. The goal of this study was to determine the morphology and morphometrics of the dromedary camel's inner ear and how it influences hearing accommodation and equilibrium in the desert environment. Materials and methods: Gross morphology, computed tomography images, and the endocast were used to show the inner ear morphology. A caliper and ImageJ software were used to take measurements on a plastic endocast. Results: The presence of the subarcuate fossa, flat cochlea, radii curvature of the semicircular canals, particularly the lateral semicircular canal, orthogonality, and the union between the semicircular canals, along with slightly increased saccule and utricle size, maintains camel balance on sandy ground, even during heavy sandstorms. The cochlear basilar membrane length and cochlea radii ratio aided low-frequency hearing and perception over a wide octave range. Conclusion: The camel's cochlear characteristics revealed a lengthy basilar membrane, a high radii ratio, 3.0 cochlear canal turns, and a very broad cochlea. The orthogonality of the semicircular canals, the high curvature of the lateral semicircular canal, the presence of the subarcuate fossa, and the confluence between the lateral and posterior semicircular canal were particular specifications that allowed the inner ear of the camel to adapt to desert living. [ABSTRACT FROM AUTHOR]

Background: Uncoupling protein 2 (UCP2), activated by excessive reactive oxygen species (ROS) in vivo, has the dual effect of reducing ROS to protect against oxidative stress and reducing ATP production to regulate cellular metabolism. Both the UCP2 and ROS are increased in cochleae in age-related hearing loss (ARHL). However, the role of UCP2 in sensory hair cells in ARHL remains unclear. Methods: Male C57BL/6 J mice were randomly assigned to an 8-week-old group (Group 1), a 16-week-old group (Group 2), a 16-week-old + adeno-associated virus-inner ear (AAV-ie) group (Group 3), and a 16-week-old + AAV-ie-UCP2 group (Group 4). Mice aged 8 weeks were administrated with AAV-ie-GFP or AAV-ie-UCP2 via posterior semicircular canal injection. Eight weeks after this viral intervention, hearing thresholds and wave-I amplitudes were tested by auditory brainstem response (ABR). Subsequently, the cochlear basilar membrane was dissected for investigation. The number of hair cells and inner hair cell (IHC) synapses, the level of ROS, and the expression of AMP-activated protein kinase α (AMPKα), were assessed by immunofluorescence staining. In addition, mitochondrial function was determined, and the expression of AMPKα and UCP2 proteins was further evaluated using western blotting. Results: Mice with early-onset ARHL exhibited enhanced oxidative stress and loss of outer hair cells and IHC synapses, while UCP2 overexpression aggravated hearing loss and cochlear pathophysiological changes in mice. UCP2 overexpression resulted in a notable decrease in the number of IHCs and IHC synapses, caused ATP depletion and excessive ROS generation, increased AMPKα protein levels, and promoted IHC apoptosis, especially in the apical and middle turns of the cochlea. Conclusion: Collectively, our data suggest that UCP2 overexpression may cause mitochondrial dysfunction via energy metabolism, which activates mitochondrion-dependent cellular apoptosis and leads to IHC loss, ultimately exacerbating ARHL. [ABSTRACT FROM AUTHOR]

The mammalian ear embeds a cellular amplifier that boosts sound-induced hydromechanical waves as they propagate along the cochlea. The operation of this amplifier is not fully understood and is difficult to disentangle experimentally. In the prevailing view, cochlear waves are amplified by the piezo-electric action of the outer hair cells (OHCs), whose cycle-by-cycle elongations and contractions inject power into the local motion of the basilar membrane (BM). Concomitant deformations of the opposing (or "top") side of the organ of Corti are assumed to play a minor role and are generally neglected. However, analysis of intracochlear motions obtained using optical coherence tomography calls this prevailing view into question. In particular, the analysis suggests that (i) the net local power transfer from the OHCs to the BM is either negative or highly inefficient; and (ii) vibration of the top side of the organ of Corti plays a primary role in traveling-wave amplification. A phenomenological model derived from these observations manifests realistic cochlear responses and suggests that amplification arises almost entirely from OHC-induced deformations of the top side of the organ of Corti. In effect, the model turns classic assumptions about spatial impedance relations and power-flow direction within the sensory epithelium upside down. [ABSTRACT FROM AUTHOR]

The basilar membrane in the cochlea can be modeled as an array of fluid coupled segments driven by stapes vibration and by the undamping nonlinear force simulating cochlear amplification. If stimulated with two tones, the model generates additional tones due to nonlinear distortion. These distortion products (DPs) can be transmitted into the ear canal and produce distortion-product otoacoustic emissions (DPOAEs) known to be generated in the healthy ear of various vertebrates. This study presents a solution for DPs in a two-dimensional nonlinear cochlear model with cochlear roughness—small irregularities in the impedance along the basilar membrane, which may produce additional DPs due to coherent reflection. The solution allows for decomposition of various sources of DPs in the model. In addition to the already described nonlinear-distortion and coherent-reflection mechanisms of DP generation, this study identifies a long-latency DPOAE component due to perturbation of nonlinear force. DP wavelets that are coherently reflected due to impedance irregularities travel toward the stapes across the primary generation region of DPs and there evoke perturbation of the nonlinear undamping force. The ensuing DP wavelets have opposite phase to the wavelets arising from coherent reflection, which results in partial cancellation of the coherent-reflection DP wavelets. [ABSTRACT FROM AUTHOR]

Multiple propagation modes progress along the basilar membrane and Reissner's membrane, called basilar membrane mode (BM mode) and Reissner's membrane mode (RM mode), respectively. This study focuses on the effects of the RM mode on the hearing process and investigates the difference in the attenuation characteristics between the RM and BM modes in the vicinity of the cochlea base by using modal analysis. Results indicated that the RM mode has fewer effects on the hearing process, except otoacoustic emissions, due to its bigger attenuation constant than the BM mode in the vicinity of the cochlea base. The structural dependency of the attenuation constant of the RM mode is also investigated., Competing Interests: None, (Copyright: © Journal of Biomedical Physics and Engineering.)

Cochlear sensitivity, essential for communication and exploiting the acoustic environment, results from sensory-motor outer hair cells (OHCs) operating in a structural scaffold of supporting cells and extracellular cortilymph within the organ of Corti (OoC). Cochlear sensitivity control is hypothesized to involve interaction between the OHCs and OoC supporting cells (e.g., Deiters' cells [DCs] and outer pillar cells [OPCs]), but this has never been established in vivo. Here, we conditionally expressed channelrhodopsins (ChR2) specifically in male and female mouse DCs and OPCs. Illumination of the OoC activated the nonselective ChR2 cation conductance and depolarized DCs when measured in vivo and in isolated OoC. Measurements of sound-induced cochlear mechanical and electrical responses revealed that OoC illumination suppressed the normal functions of OoC supporting cells transiently and reversibly. OoC illumination blocked normally occurring continuous minor adjustments of tone-evoked basilar membrane displacements over their entire dynamic range and OHC voltage responses to tones at levels and frequencies subject to cochlear amplification. OoC illumination altered the OHC mechanoelectrical transduction conductance operating point, which reversed the asymmetry of OHC voltage responses to high level tones. OoC illumination accelerated recovery from temporary loud sound-induced acoustic desensitization. We concluded that DCs and OPCs are involved in both the control of cochlear responses (which are essential for normal hearing) and the recovery from temporary acoustic desensitization. This is the first direct in vivo evidence for the interdependency of the structural, mechanical, and electrochemical arrangements of OHCs and OoC supporting cells that together provide fine control of cochlear responses. [ABSTRACT FROM AUTHOR]

Combining aminoglycosides and loop diuretics often serves as an effective ototoxic approach to deafen experimental animals. The treatment results in rapid hair cell loss with extended macrophage presence in the cochlea, creating a sterile inflammatory environment. Although the early recruitment of macrophages is typically neuroprotective, the delay in the resolution of macrophage activity can be a complication if the damaged cochlea is used as a model to study subsequent therapeutic strategies. Here, we applied a high dose combination of systemic gentamicin and furosemide in C57 BL/6 and CBA/CaJ mice and studied the ototoxic consequences in the cochlea, including hair cell survival, ribbon synaptic integrity, and macrophage activation up to 15-day posttreatment. The activity of macrophages in the basilar membrane was correlated to the severity of cochlear damage, particularly the hair cell damage. Comparatively, C57 BL/6 cochleae were more vulnerable to the ototoxic challenge with escalated macrophage activation. In addition, the ribbon synaptic deterioration was disproportionately limited when compared to the degree of outer hair cell loss in CBA/CaJ mice. The innate and differential otoprotection in CBA/CaJ mice appears to be associated with the rapid activation of cochlear macrophages and a certain level of synaptogenesis after the combined gentamicin and furosemide treatment. [ABSTRACT FROM AUTHOR]

Background. We attempt to discuss the function of self-made prescription compound Rhodiola rosea on the kidneys of rats with type 2 diabetic nephropathy (DN), through studying the effects of self-made rescription compound Rhodiola rosea on the ultrastructure of podocytes in rats with DN. Methods. DN rat model was established by streptozotocin. The successfully modeled rats were divided into 4 groups, DN group, compound Rhodiola low-dose group, medium-dose group, and high-dose group. Compound Rhodiola low-dose group, medium-dose group, and high-dose group were administered for 8 weeks, and the DN group and the blank control group were administered with normal saline. The podocyte count, podocyte width, podocyte fusion rate, and average thickness of glomerular basement membrane were compared in each group, and the ultrastructural changes in podocytes were observed by transmission electron microscope. Results. Compared with the normal control group, the number of podocytes in the DN group remarkably reduced, but the width level of podocyte, the fusion rate of podocyte, and the average thickness of basilar membrane remarkably increased (P < 0.05). Compared with the DN group, the number of podocytes in the high-, medium-, and low-dose groups increased remarkably, but the width level of podocyte, the fusion rate of podocyte, and the average thickness of basilar membrane decreased remarkably (P < 0.05). Compared with the low-dose group, the number of podocytes in the high-dose group and the medium-dose group increased remarkably, but the width of podocyte, the fusion rate of podocyte, as well as the average thickness of basilar membrane remarkably reduced (P < 0.05). Various indicators of high- and medium-dose groups had no statistical difference (P > 0.05). Conclusions. Self-made prescription compound Rhodiola rosea can promote the recovery of podocyte in DN rat and protect their kidney. [ABSTRACT FROM AUTHOR]

In the mammalian auditory system, frequency discrimination depends on numerous morphological and physiological properties of the organ of Corti, which gradually change along the apex-to-base (tonotopic) axis of the organ. For example, the basilar membrane stiffness changes tonotopically, thus affecting the tuning properties of individual hair cells. At the molecular level, those frequency-specific characteristics are mirrored by gene expression gradients; however, the molecular mechanisms controlling tonotopic gene expression in the mouse cochlea remain elusive. Through analyzing single-cell RNA sequencing (scRNA-seq) data from E12.5 and E14.5 time points, we predicted that morphogens, rather than a cell division-associated mechanism, confer spatial identity in the extending cochlea. Subsequently, we reconstructed the developing cochlea in 3D space from scRNA-seq data to investigate the molecular pathways mediating positional information. The retinoic acid (RA) and hedgehog pathways were found to form opposing apex-to-base gradients, and functional interrogation using mouse cochlear explants suggested that both pathways jointly specify the longitudinal axis. [Display omitted] • 3D reconstruction of the developing cochlear duct from scRNA-seq data • Morphogens, not cell cycle exit, confer tonotopic information in the cochlea • Opposing RA and SHH gradients control apex-to-base gene expression in the cochlea Wang and Chakraborty et al. demonstrate that morphogens rather than a timing-related mechanism mediate positional information along the apex-to-base axis of the murine cochlea. Moreover, two morphogens, retinoic acid and sonic hedgehog, were identified to form opposing morphogen gradients, thereby controlling spatial gene expression along the apex-to-base axis. [ABSTRACT FROM AUTHOR]

Objective: To establish an animal model of noise-induced hidden hearing loss (NIHHL), evaluate the dynamic changes in cochlear ribbon synapses and cochlear hair cell morphology, and observe the involvement of the SIRT1/PGC-1α signaling pathway in NIHHL. Methods: Male guinea pigs were randomly divided into three groups: control group, noise exposure group, and resveratrol treatment group. Each group was divided into five subgroups: the control group and 1 day, 1 week, 2 weeks, and 1 month post noise exposure groups. The experimental groups received noise stimulation at 105 dB SPL for 2 h. Hearing levels were examined by auditory brainstem response (ABR). Ribbon synapses were evaluated by inner ear basilar membrane preparation and immunofluorescence. The cochlear morphology was observed using scanning electron microscopy. Western blotting analysis and immunofluorescence was performed to assess the change of SIRT1/PGC-1α signaling. Levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), ATP and SIRT1 activity were measured using commercial testing kits. Results: In the noise exposure group, hearing threshold exhibited a temporary threshold shift (TTS), and amplitude of ABR wave I decreased irreversibly. Ribbon synapse density decreased after noise exposure, and the stereocilia were chaotic and then returned to normal. The expression and activity of SIRT1 and PGC-1α protein was lower than that in the control group. SOD, CAT and ATP were also influenced by noise exposure and were lower than those in the control group, but MDA showed no statistical differences compared with the control group. After resveratrol treatment, SIRT1 expression and activity showed a significant increase after noise exposure, compared with the noise exposure group. In parallel, the PGC-1α and antioxidant proteins were also significantly altered after noise exposure, compared with the noise exposure group. The damage to the ribbon synapses and the stereocilia were attenuated by resveratrol as well. More importantly, the auditory function, especially ABR wave I amplitudes, was also promoted in the resveratrol treatment group. Conclusion: The SIRT1/PGC-1α signaling pathway and oxidative stress are involved in the pathogenesis of NIHHL and could be potential therapeutical targets in the future. [ABSTRACT FROM AUTHOR]

Based on the modern microelectromechanical systems technology, we present a revolutionary miniaturized artificial cochlear sensory epithelium for future implantation tests on guinea pigs. The device was curved to fit the spiral structure of the cochlea and miniaturized to a maximum dimension of <1 mm to be implanted in the cochlea. First, the effect of the curved configuration on the oscillation characteristics of a trapezoidal membrane was evaluated using the relatively larger devices, which had a trapezoidal and a comparable curved shape designed for high-precision in vitro measurements. Both experimental and numerical analyses were used to determine the resonance frequencies and positions, and multiple oscillation modes were clearly observed. Because the maximum oscillation amplitude positions, i.e., the resonance positions, differed depending on the resonance frequencies in both trapezoidal and curved membrane devices, the sound frequency was determined based on the resonance position, thus reproducing the frequency selectivity of the basilar membrane in the organ of Corti. Furthermore, the resonance frequencies and positions of these two devices with different configurations were determined to be quantitatively consistent and similar in terms of mechanical dynamics. This result shows that despite a curved angle of 50–60°, the effect of the curved shape on oscillation characteristics was negligible. Second, the nanometer-scale oscillation of the miniaturized device was successfully measured, and the local resonance frequency in air was varied from 157 to 277 kHz using an experimental system that could measure the amplitude distribution in a two-dimensional (2D) plane with a high accuracy and reproducibility at a high speed. The miniaturized device developed in this study was shown to have frequency selectivity, and when the device was implanted in the cochlea, it was expected to discriminate frequencies in the same manner as the basilar membrane in the biological system. This study established methods for fabricating and evaluating the miniaturized device, and the proposed miniaturized device in a curved shape demonstrated the feasibility of next-generation cochlear implants. [ABSTRACT FROM AUTHOR]

The scalar position of the electrode array is assumed to be associated with auditory performance after cochlear implantation. We propose a new method that can be routinely applied in clinical practice to assess the position of an electrode array. Ten basilar membrane templates were generated using micro-computed tomography (micro-CT), based on the dimensions of 100 cochleae. Five surgeons were blinded to determine the position of the electrode array in 30 cadaveric cochleae. The procedure consisted of selecting the appropriate template based on cochlear dimensions, merging the electrode array reconstruction with the template using four landmarks, determining the position of the array according to the template position, and comparing the results obtained to histology data. The time taken to analyze each implanted cochlea was approximately 12 min. We found that, according to histology, surgeons were in almost perfect agreement when determining an electrode translocated to the scala vestibuli with the perimodiolar MidScala array (Fleiss' kappa (κ) = 0.82), and in moderate agreement when using the lateral wall EVO array (κ = 0.42). Our data indicate that an adapted basilar membrane template can be used as a rapid and reproducible method to assess the position of the electrode array after cochlear implantation. [ABSTRACT FROM AUTHOR]