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Nobel Laureate von Békésy first presented traveling wave theory, which explains the vibration mechanism of the basilar membrane (BM) of cochlea in 1960, and thus the mysterious veil of passive phonoreceptive mechanism of human cochlea was unveiled. However, the interpretation of active phonoreceptive mechanism of human cochlea has been a major medical problem for mankind. The active mechanism can be reflected in structures and the perilymph where a series of complex coupling nonlinear motion process is observed in the cochlea. Because the cochlea is small and complex, vibration data of the whole BM are not yet available from existing experiments. To address the problem, first, the motion equations of the organ of Corti (OHC) are established, and the circuit equations of the outer hair cells (OHCs) in the perilymph and the relationship between the motion of the outer hair cells and the electromotile force are derived. Then the active feedback force on the BM is obtained. Finally, an analytical-numerical combination model, where both macrostructures and microstructures of cochlea are included, is established. The model not only vividly depicts the spatial helical body and biological materials of the cochlea but also reflects the fluid-solid coupling nonlinear motion of cochlear structures in the electrical environment. Thus, the active hearing mechanism of cochlea is revealed. [ABSTRACT FROM AUTHOR]

The term "roughness" describes the random heterogeneity in the mechanisms of splitting the cochlea along the basilar membrane (BM) and this characteristic (heterogeneity) may determine the emission status at different levels of stimulation. In the context of this research work, the relationship between levels of severity and roughness was studied, and this study was carried out using the nonlinear model by monitoring the transient-evoked otoacoustic emissions (TEOAEs) in each change. It was showed that otoacoustic emissions (OAEs) were affected by changes in roughness and classification of low, medium and high stimulation levels. [ABSTRACT FROM AUTHOR]

Introduction: Auditory brainstem response (ABR) is one of the commonly used methods in clinical settings to evaluate the hearing sensitivity and auditory function. The current ABR measurement usually adopts click sound as the stimuli. However, there may be partial ABR amplitude attenuation due to the delay characteristics of the cochlear traveling wave along the basilar membrane. To solve that problem, a swept-tone method was proposed, in which the show-up time of different frequency components was adjusted to compensate the delay characteristics of the cochlear basilar membrane; therefore, different ABR subcomponents of different frequencies were synchronized. Methods: The normal hearing group, moderate sensorineural hearing loss group, and severe sensorineural hearing loss group underwent click ABR and swept-tone ABR with different stimulus intensities. The latencies and amplitudes of waves I, III, and V in 2 detections were recorded. Results: It was found that the latency of each of the recorded I, III, and V waves detected by swept-tone ABR was shorter than that by click ABR in both the control group and experimental groups. In addition, the amplitude of each of the recorded I, III, and V waves, except V waves under 60 dB nHL in the moderate sensorineural hearing loss group, detected by swept-tone ABR was larger than that by click ABR. The results also showed that the swept-tone ABR could measure the visible V waves at lower stimulus levels in the severe sensorineural hearing loss group. Conclusion: Swept-tone improves the ABR waveforms and helps to obtain more accurate threshold to some extent. Therefore, the proposed swept-tone ABR may provide a new solution for better morphology of ABR waveform, which can help to make more accurate diagnosis about the hearing functionality in the clinic. [ABSTRACT FROM AUTHOR]

An artificial basilar membrane (ABM) is an acoustic transducer that mimics the mechanical frequency selectivity of the real basilar membrane, which has the potential to revolutionize current cochlear implant technology. While such ABMs can be potentially realized using piezoelectric, triboelectric, and capacitive transduction methods, it remains notoriously difficult to achieve resistive ABM due to the poor frequency discrimination of resistive‐type materials. Here, a point crack technology on noncracking vertically aligned gold nanowire (V‐AuNW) films is reported, which allows for designing soft acoustic sensors with electric signals in good agreement with vibrometer output—a capability not achieved with corresponding bulk cracking system. The strategy can lead to soft microphones for music recognition comparable to the conventional microphone. Moreover, a soft resistive ABM is demonstrated by integrating eight nanowire‐based sensor strips on a soft trapezoid frame. The wearable ABM exhibits high‐frequency selectivity in the range of 319–1951 Hz and high sensitivity of 0.48–4.26 Pa−1. The simple yet efficient fabrication in conjunction with programmable crack design indicates the promise of the methodology for a wide range of applications in future wearable voice recognition devices, cochlea implants, and human–machine interfaces. [ABSTRACT FROM AUTHOR]

The article presents a study that explores how Emilin 2 promotes the mechanical gradient of the cochlear basilar membrane and resolution of frequencies in sound. It mentions that detection of different frequencies in sound accomplished with remarkable precision by the basilar membrane (BM), an elastic, ribbon-like structure with graded stiffness along the cochlear spiral.

Stimulus-frequency otoacoustic emissions (SFOAEs) are generated by coherent reflection of forward traveling waves by perturbations along the basilar membrane. The strongest wavelets are backscattered near the place where the traveling wave reaches its maximal amplitude (tonotopic place). Therefore, the SFOAE group delay might be expected to be twice the group delay estimated in the cochlear filters. However, experimental data have yielded steady-state SFOAE components with near-zero latency. A cochlear model is used to show that short-latency SFOAE components can be generated due to nonlinear reflection of the compressor or suppressor tones used in SFOAE measurements. The simulations indicate that suppressors produce more pronounced short-latency components than compressors. The existence of nonlinear reflection components due to suppressors can also explain why SFOAEs can still be detected when suppressors are presented more than half an octave above the probe-tone frequency. Simulations of the SFOAE suppression tuning curves showed that phase changes in the SFOAE residual as the suppressor frequency increases are mostly determined by phase changes of the nonlinear reflection component. [ABSTRACT FROM AUTHOR]

In mammals, audition is triggered by travelling waves that are evoked by acoustic stimuli in the cochlear partition, a structure containing sensory hair cells and a basilar membrane. When the cochlea is stimulated by a pure tone of low frequency, a static offset occurs in the vibration in the apical turn. In the high-frequency region at the cochlear base, multi-tone stimuli induce a quadratic distortion product in the vibrations that suggests the presence of an offset. However, vibrations below 100 Hz, including a static offset, have not been directly measured there. We therefore constructed an interferometer for detecting motion at low frequencies including 0 Hz. We applied the interferometer to record vibrations from the cochlear base of guinea pigs in response to pure tones. When the animals were exposed to sound at an intensity of 70 dB or higher, we recorded a static offset of the sinusoidally vibrating cochlear partition by more than 1 nm towards the scala vestibuli. The offset's magnitude grew monotonically as the stimuli intensified. When stimulus frequency was varied, the response peaked around the best frequency, the frequency that maximised the vibration amplitude at threshold sound pressure. These characteristics are consistent with those found in the low-frequency region and are therefore likely common across the cochlea. The offset diminished markedly when the somatic motility of mechanosensitive outer hair cells, the force-generating machinery that amplifies the sinusoidal vibrations, was pharmacologically blocked. Therefore, the partition offset appears to be linked to the electromotile contraction of outer hair cells. [ABSTRACT FROM AUTHOR]

The classic view of cochlear partition (CP) motion, generalized to be for all mammals, was derived from basal-turn measurements in laboratory animals. Recently, we reported motion of the human CP in the cochlear base that differs substantially from the classic view. We described a human soft tissue "bridge" (non-existent in the classic view) between the osseous spiral lamina (OSL) and basilar membrane (BM), and showed how OSL and bridge move in response to sound. Here, we detail relevant human anatomy to better understand the relationship between form and function. The bridge and BM have similar widths that increase linearly from base to apex, whereas the OSL width decreases from base to apex, leading to an approximately constant total CP width throughout the cochlea. The bony three-dimensional OSL microstructure, reconstructed from unconventionally thin, 2-μm histological sections, revealed thin, radially wide OSL plates with pores that vary in size, extent, and distribution with cochlear location. Polarized light microscopy revealed collagen fibers in the BM that spread out medially through the bridge to connect to the OSL. The long width and porosity of the OSL may explain its considerable bending flexibility. The similarity of BM and bridge widths along the cochlea, both containing continuous collagen fibers, may make them a functional unit and allow maximum CP motion near the bridge-BM boundary, as recently described. These anatomical findings may help us better understand the motion of the structures surrounding the organ of Corti and how they shape the input to the cochlear sensory mechanism. [ABSTRACT FROM AUTHOR]

The cochlea's wave-based signal processing allows it to efficiently decompose a complex acoustic waveform into frequency components. Because cochlear responses are nonlinear, the waves arising from one frequency component of a complex sound can be altered by the presence of others that overlap with it in time and space (e.g., two-tone suppression). Here, we investigate the suppression of basilar-membrane (BM) velocity responses to a transient signal (a test click) by another click or tone. We show that the BM response to the click can be reduced when the stimulus is shortly preceded or followed by another (suppressor) click. More surprisingly, the data reveal two curious dependencies on the interclick interval, Δt. First, the temporal suppression curve (amount of suppression vs. Δt) manifests a pronounced and nearly periodic microstructure. Second, temporal suppression is generally strongest not when the two clicks are presented simultaneously (Δt = 0), but when the suppressor click precedes the test click by a time interval corresponding to one to two periods of the best frequency (BF) at the measurement location. By systematically varying the phase of the suppressor click, we demonstrate that the suppression microstructure arises from alternating constructive and destructive interference between the BM responses to the two clicks. And by comparing temporal and tonal suppression in the same animals, we test the hypothesis that the asymmetry of the temporal-suppression curve around Δt = 0 stems from cochlear dispersion and the well-known asymmetry of tonal suppression around the BF. Just as for two-tone suppression, BM responses to clicks are most suppressed by tones at frequencies just above the BF of the measurement location. On average, the frequency place of maximal suppressibility of the click response predicted from temporal-suppression data agrees with the frequency at which tonal suppression peaks, consistent with our hypothesis. [ABSTRACT FROM AUTHOR]

It has been demonstrated that isolated auditory sensory cells, outer hair cells, can generate distortion products at low frequencies. It remains unknown, however, whether or not motile outer hair cells are able to generate two-tone distortion at high frequencies in living cochleae under the mechanical loads caused by surounding tissues and fluids. By measuring sub-nanometer vibration directly from the apical ends of outer hair cells using a custom-built heterodyne low-coherence interferometer, here we show outer hair cell-generated two-tone distortion in reticular lamina motion in the living cochlea. Reticular-lamina distortion is significantly greater and occurs at a broader frequency range than that of the basilar membrane. Contrary to expectations, our results indicate that motile outer hair cells are capable of generating two-tone distortion in vivo not only at the locations tuned to primary tones but also at a broad region basal to these locations. Ren et al. used an in house heterodyne low-coherence interferometer to measure sub-nanometer vibrations, a proxy for distortion products, in living cochleae of gerbils. They were able to locate the generation source of the outer hair cell in the reticular lamina versus the basilar membrane in vivo. [ABSTRACT FROM AUTHOR]

Background: Despite significant anatomical variation amongst patients, cochlear implant frequency-mapping has traditionally followed a patient-independent approach. Basilar membrane (BM) length is required for patient-specific frequency-mapping, however cochlear duct length (CDL) measurements generally extend to the apical tip of the entire cochlea or have no clearly defined end-point. By characterizing the length between the end of the BM and the apical tip of the entire cochlea (helicotrema length), current CDL models can be corrected to obtain the appropriate BM length. Synchrotron radiation phase-contrast imaging has made this analysis possible due to the soft-tissue contrast through the entire cochlear apex. Methods: Helicotrema linear length and helicotrema angular length measurements were performed on synchrotron radiation phase-contrast imaging data of 14 cadaveric human cochleae. On a sub-set of six samples, the CDL to the apical tip of the entire cochlea (CDLTIP) and the BM length (CDLBM) were determined. Regression analysis was performed to assess the relationship between CDLTIP and CDLBM. Results: The mean helicotrema linear length and helicotrema angular length values were 1.6 ± 0.9 mm and 67.8 ± 37.9 degrees, respectively. Regression analysis revealed the following relationship between CDLTIP and CDLBM: CDLBM = 0.88(CDLTIP) + 3.71 (R2 = 0.995). Conclusion: This is the first known study to characterize the length of the helicotrema in the context of CDL measurements. It was determined that the distance between the end of the BM and the tip of the entire cochlea is clinically consequential. A relationship was determined that can predict the BM length of an individual patient based on their respective CDL measured to the apical tip of the cochlea. [ABSTRACT FROM AUTHOR]

The three modes of auditory stimulation (air, bone and soft tissue conduction) at threshold intensities are thought to share a common excitation mechanism: the stimuli induce passive displacements of the basilar membrane propagating from the base to the apex (slow mechanical traveling wave), which activate the outer hair cells, producing active displacements, which sum with the passive displacements. However, theoretical analyses and modeling of cochlear mechanics provide indications that the slow mechanical basilar membrane traveling wave may not be able to excite the cochlea at threshold intensities with the frequency discrimination observed. These analyses are complemented by several independent lines of research results supporting the notion that cochlear excitation at threshold may not involve a passive traveling wave, and the fast cochlear fluid pressures may directly activate the outer hair cells: opening of the sealed inner ear in patients undergoing cochlear implantation is not accompanied by threshold elevations to low frequency stimulation which would be expected to result from opening the cochlea, reducing cochlear impedance, altering hydrodynamics. The magnitude of the passive displacements at threshold is negligible. Isolated outer hair cells in fluid display tuned mechanical motility to fluid pressures which likely act on stretch sensitive ion channels in the walls of the cells. Vibrations delivered to soft tissue body sites elicit hearing. Thus, based on theoretical and experimental evidence, the common mechanism eliciting hearing during threshold stimulation by air, bone and soft tissue conduction may involve the fast-cochlear fluid pressures which directly activate the outer hair cells. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Temporal bone (TB) studies are essential during the development of new arrays. Postoperative cochlear histology is still regarded as golden standard for the assessment of electrode localization and trauma though it is time consuming, expensive and technically very demanding. The aim of this study is to investigate whether pre-operative evacuation of perilymph improve the assessment of electrode localization and insertion trauma in TBs applying fusion imaging. The results were compared to a prior validated image fusion technique based on the quantification of the electrode placement. MATERIALS and METHODS: 12 prototype electrodes were implanted in fresh frozen TBs. The perilymph was evacuated from the scale prior to pre-operative cone-beam computer tomography (CBCT). The TB were then immersed in Ringer solution to rehydrated both scalae. After electrode insertion post-operative CBCT were obtained. 3D fusions of the pre- and postoperative registration were reconstructed. The electrode localization with respect to the basilar membrane was visually assessed. RESULTS: The visualization of the BM on the pre-operative scans was achieved beyond the second turn in all TBs. The visual assessment was found to be as accurate as the previously validated fusion technique. There was no statistically significant difference between the methods (p=0.564). The image reconstructions and evaluations, however, were faster to perform and the insertion results are immediately available. CONCLUSION: CBCT in combination with pre- and postoperative image fusion is an accurate method for the post-operative assessment of insertion trauma in TBs. This new application facilitates the identification of the BM and allows for a visual assessment of insertion trauma. [ABSTRACT FROM AUTHOR]

Estimation of audiograms for marine mammals, particularly cetaceans, is a challenging task due to regulatory restrictions, sample availability, and the general paucity of data regarding the anatomical and physiological characteristics of the auditory system in these species. At present, we are characterizing point stiffness of the basilar membrane (BM), the principal resonating structure in the cochlea that supports hair cells of the organ of Corti. The ultimate goal of this project is to correlate point-stiffness measurements with accurate position-based estimates of the frequency response distribution along the BM in multiple cetacean species. Herein, we present the preliminary step of a method for estimating the length along the BM at which point-stiffness measurements were taken to determine frequency-stiffness correlates in one species, the harbor porpoise (Phocoena phocoena), which is also a "control" species for which there are live animal audiograms. A species-specific model of cochlear geometries and BM spirals were aligned and fitted to the individual curvature of each specimen on high-resolution photographs of the experimental point-stiffness measurement sites. This method produces reliable estimates of the location along the BM at which point-stiffnesses were recorded, with precisions of approximately 0.33%, providing a reliable means of localizing point-stiffness responses for improving audiogram estimation. [ABSTRACT FROM AUTHOR]

A lack of sleep is linked with a range of inner ear diseases, including hearing loss and tinnitus. Here, we used a mouse model to investigate the effects of sleep deprivation (SD) on noise vulnerability, and explored the mechanisms that might be involved in vitro , focusing particularly corticosterone levels and autophagic flux in cells. Female BALB/c mice were divided into six groups [control, acoustic trauma (AT)-alone, 1 day (d) SD-alone, 1d SD pre-AT, 5d SD-alone, and 5d SD pre-AT]. Cochlear damage was then assessed by analyzing auditory brainstem response (ABR), and by counting outer hair cells (OHCs) and the synaptic ribbons of inner hair cells (IHCs). In addition, we measured levels of serum corticosterone and autophagy protein expression in the basilar membranes by ELISA kits, and western blotting, respectively. We found that SD-alone temporarily elevated ABR wave I amplitude, but had no permanent effect on hearing level or IHC ribbon numbers. Combined with AT, the number of synaptic ribbons in the 1d SD pre-AT group was significantly higher than that in the AT-alone group, whereas the 5d SD pre-AT group showed more severe synaptopathy, and a greater loss of OHCs after 2 weeks than the other experimental groups exposed to noise. Correspondingly, the levels of corticosterone in the AT-alone group were higher than those of the 1d SD pre-AT group, but lower than those of the 5d SD pre-AT group. The 1d SD pre-AT group showed a marked elevation in the expression of microtubule-associated protein 1 light chain 3B (LC3B), whereas the AT-alone group exhibited only a mild increase. In contrast, the levels of LC3B did not change in the 5d SD pre-AT group. Experiments with HEI-OC-1 cells and cochlear basilar membrane cultures showed that high-concentrations of dexamethasone, and the inhibition of autophagy, aggravated cellular apoptosis induced by oxidative stress. In conclusion, noise-induced synaptopathy and hair cell loss can be mitigated by preceding 1d SD, but will be aggravated by preceding 5d SD. These findings may be attributable to corticosterone levels and the extent of autophagy. [ABSTRACT FROM AUTHOR]

With the rapid development of nanotechnology, engineered nanomaterials (ENMs) have been applied in many fields, such as food industry, biomedicine, and so on. However, the study on the health and safety implications of ENMs is still insufficient. Previous studies have shown that nanoparticles under acute or chronic exposure could be transported and accumulated in various organs and tissues, resulting in adverse effects or systemic toxicity. Among these, the kidney is one of the main organs that exposed ENMs will target through different routes. One of the important functions of the kidney is to discharge metabolic wastes and exogenous substances from the blood circulation of the whole body. During ENM exposure, the kidney may become vulnerable to toxicity. Studies have suggested that nanoparticles exposed to the kidney could provoke glomerular swelling, basilar membrane thickening, degeneration, and necrosis of renal tubular cells. These adverse effects of nanoparticles on the kidney may be related to their induced oxidative stress, inflammation, autophagy, DNA damage, and ER stress. This review aims to examine current studies on ENM-induced nephrotoxicity, with the focus on elucidating the potential molecular mechanisms of nanoparticle-induced toxicity on the kidney, which will further facilitate the safer design of ENMs and their applications. [ABSTRACT FROM AUTHOR]

Bats are among the most recognizable, numerous, and widespread of all mammals. But much of their fossil record is missing, and bat origins remain poorly understood, as do the relationships of early to modern bats. Here, we describe a new early Eocene bat that helps bridge the gap between archaic stem bats and the hyperdiverse modern bat radiation of more than 1,460 living species. Recovered from ∼50 million-year-old cave sediments in the Quercy Phosphorites of southwestern France, Vielasia sigei 's remains include a near-complete, three-dimensionally preserved skull—the oldest uncrushed bat cranium yet found. Phylogenetic analyses of a 2,665 craniodental character matrix, with and without 36.8 kb of DNA sequence data, place Vielasia outside modern bats, with total evidence tip-dating placing it sister to the crown clade. Vielasia retains the archaic dentition and skeletal features typical of early Eocene bats, but its inner ear shows specializations found in modern echolocating bats. These features, which include a petrosal only loosely attached to the basicranium, an expanded cochlea representing ∼25% basicranial width, and a long basilar membrane, collectively suggest that the kind of laryngeal echolocation used by most modern bats predates the crown radiation. At least 23 individuals of V. sigei are preserved together in a limestone cave deposit, indicating that cave roosting behavior had evolved in bats by the end of the early Eocene; this period saw the beginning of significant global climate cooling that may have been an evolutionary driver for bats to first congregate in caves. [Display omitted] • A new bat species is described from a 50-million-year-old cave deposit in France • Its well-preserved fossils include the oldest uncrushed skull of a bat yet known • This stem bat appears to have been capable of advanced (laryngeal) echolocation • The fossils suggest that advanced echolocation predates the crown bat radiation When and how echolocation first evolved in bats is contentious. Hand et al. report on an uncrushed, 50-million-year-old bat skull that provides significant new data to inform the debate. Measurements of the inner ear of the French stem bat Vielasia suggest that advanced (laryngeal) echolocation may have evolved before the crown bat radiation. [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.

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., (© 2023 Acoustical Society of America.)

Gammatones have had a long history in auditory studies, and recent theoretical work suggests they may play an important role in cochlear mechanics as well. Following this lead, the present paper takes five examples of basilar membrane impulse responses and uses a curve-fitting algorithm to decompose them into a number of discrete gammatones. The limits of this ‘sum of gammatones’ (SOG) method to accurately represent the impulse response waveforms were tested and it was found that at least two and up to six gammatones could be isolated from each example. Their frequencies were stable and largely independent of stimulus parameters. The gammatones typically formed a regular series in which the frequency ratio between successive members was about 1.1. Adding together the first few gammatones in a set produced beating-like waveforms which mimicked waxing and waning, and the instantaneous frequencies of the waveforms were also well reproduced, providing an explanation for frequency glides. Consideration was also given to the impulse response of a pair of elastically coupled masses—the basis of two-degree-of-freedom models comprised of coupled basilar and tectorial membranes—and the resulting waveform was similar to a pair of beating gammatones, perhaps explaining why the SOG method seems to work well in describing cochlear impulse responses. A major limitation of the SOG method is that it cannot distinguish a waveform resulting from an actual physical resonance from one derived from overfitting, but taken together the method points to the presence of a series of closely spaced local resonances in the cochlea.