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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 Lgr5

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.

Exposure to noise trauma, such as that from improvised explosive devices, can lead to sensorineural hearing loss and a reduced quality of life. In order to elucidate the mechanisms underlying noise-induced hearing loss, we have adapted optical coherence tomography (OCT) for real-time cochlear visualization in live mice after blast exposure. We demonstrated that endolymphatic hydrops develops following blast injury, and that this phenomenon may be associated with glutamate excitotoxicity and cochlear synaptopathy. Additionally, osmotic stabilization of endolymphatic hydrops partially rescues cochlear synapses after blast trauma. OCT is thus a valuable research tool for investigating the mechanisms underlying acoustic trauma and dynamic changes in endolymph volume. It may also help with the diagnosis and treatment of human hearing loss and/or vertigo in the near future.

Objective To create an aerosol containment mask (ACM) that contains aerosols during common otolaryngologic endoscopic procedures while protecting patients from environmental aerosols. Study Design Bench testing. Setting Mannequin testing. Methods The mask was designed in SolidWorks and 3-dimensional printed. Mannequins were fitted with a nebulizer to generate aerosols. Commercial particle counters were used to measure mask performance. Results The ACM has 2 ports on either side for instruments and endoscopes, a port for a filter, and a port that can evacuate aerosols contained within the mask via a standard suction pump. The mask contained aerosols on a mannequin with and without facial hair when the suction was set to 18.5 L/min. Other types of masks demonstrated substantial aerosol leakage under similar conditions. In a subsequent experiment, the ACM contained aerosols generated by a nebulizer up to the saturation of the particle detector without measurable leakage with or without suction. Conclusion The ACM will accommodate rigid and flexible endoscopes plus instruments and prevent leakage of patient-generated aerosols, thus avoiding contamination of the room and protecting health care workers from airborne contagions. Level of evidence 2.

Jorge Enrique Delgado-Hachmeister, M.D., M.P.H, M.Sc., Ph.D. 1,2, Cindy Shope 5, Daniel Chelius 3, M.D., John S. Oghalai 4, M.D., Raye L. Alford, Ph.D. 5, Bobby R. Alford† 5, M.D., Brenda Farrell, Ph.D 5, Lucy Handscomb, Ph.D. 2, Jonathan Ashmore, Ph.D. 2, Dan Jagger, Ph.D. 2, Issam Saliba, M.D. 7, Sengyoth Vilaysane, M.D. 1, Thomas Lenarz, MD 8, Anat Shahar, Ph.D. 6 Jorge E. Delgado-Hachmeister, M.D. La Salle University Mexican Faculty of Medicine Islas Marianas No. 9, Fracc. Residencial Campestre Chiluca, Atizapán de Zaragoza, C.P. 52930, Edo. de Mex., México Mobile: + 52 55 10 52 81 58 Home Phone: + 52 55 50 19 17 36 e-mail: jorgeenriquedelgadoh@hotmail.com Abstract We decided to investigate if quinine modifies the nonlinear capacitance of the mammalian outer hair cell of the hearing organ of Corti. We used isolated outer hair cells of guinea pigs and performed electrophysiological recordings. We tracked the Voltage at Peak Capacitance of the outer hair cell at different quinine concentrations and also measured the modifications of the bell-shaped curve of the outer hair cell under different quinine concentrations. We also studied if quinine induces apoptosis of the outer hair cell. We show that quinine shifts this bell-shaped curve towards depolarized potentials (>90 mV) and induces a small reduction on the gain (up to 13%). The shifts are fully reversible at low concentrations (< 1 mM) but only partially reversible at high concentrations (> 5 mM). A histological study of guinea pig OHCs confirms that quinine triggers apoptosis in a concentration dependent manner and produces large pores in the plasma membrane at high concentrations. At therapeutic concentrations of quinine that are used to treat malaria (0.04 mM) we find that quinine shifts the voltage at peak capacitance by 1.5 to 3.5 mV. This is significantly greater than observed for chloropromazine ( < 1 mV) and furosemide (no shift) at their relevant clinical concentrations. We demonstrate for the first time that the plausible mechanism by which quinine increases hearing thresholds is by partitioning into the membrane of OHCs where it affects the membrane-based motor mechanism underlying electromotility. Key Words: outer hair cells, voltage at peak capacitance, electromotility, apoptosis, quinine, amphipaths While the actions of quinine on outer hair cell physiology of mammalians have been previously investigated, it remains unknown, the precise mechanism by which quinine induces reversible tinnitus and hearing loss. Also it is unknown why quinine produces in some rare cases irreversible hearing loss. Here we provide definitive evidence that quinine at therapeutic levels for the treatment of Falciparum malaria modifies outer hair cell physiology and electromotilty and also triggers apoptosis in outer hair cells. Proving that the main mechanism by which quinine modifies hearing thresholds is by modifying outer hair cell physiology, probably by interacting with prestin. Level of Evidence: NAPlease go through this manuscript since it describes much better our findings. https://u.pcloud.link/publink/show?code=XZaSAQVZmFWjgk67A4XDbEl4wmxVKLVtlFvy

BACKGROUND AND OBJECTIVES Infants with profound hearing loss are typically considered for cochlear implantation. Many insurance providers deny implantation to children with developmental impairments because they have limited potential to acquire verbal communication. We took advantage of differing insurance coverage restrictions to compare outcomes after cochlear implantation or continued hearing aid use. METHODS Young children with deafness were identified prospectively from 2 different states, Texas and California, and followed longitudinally for an average of 2 years. Children in cohort 1 (n = 138) had normal cognition and adaptive behavior and underwent cochlear implantation. Children in cohorts 2 (n = 37) and 3 (n = 29) had low cognition and low adaptive behavior. Those in cohort 2 underwent cochlear implantation, whereas those in cohort 3 were treated with hearing aids. RESULTS Cohorts did not substantially differ in demographic characteristics. Using cohort 2 as the reference, children in cohort 1 showed more rapid gains in cognitive, adaptive function, language, and auditory skills (estimated coefficients, 0.166 to 0.403; P ≤ .001), whereas children in cohort 3 showed slower gains (−0.119 to −0.243; P ≤ .04). Children in cohort 3 also had greater increases in stress within the parent-child system (1.328; P = .02), whereas cohorts 1 and 2 were not different. CONCLUSIONS Cochlear implantation benefits children with deafness and developmental delays. This finding has health policy implications not only for private insurers but also for large, statewide, publicly administered programs. Cognitive and adaptive skills should not be used as a “litmus test” for pediatric cochlear implantation.

It is generally assumed that frequency selectivity varies along the cochlea. For example, at the base of the cochlea, which is a region sensitive to high-frequency sounds, the best frequency of a cochlear location increases toward the most basal end, that is, near the stapes. Response phases also vary along cochlear locations: At any given frequency, there is a decrease in phase lag toward the stapes. This tonotopic arrangement in the cochlea was originally described by Georg v. Békésy in a seminal series of experiments on human cadavers and has been confirmed in more recent works on live laboratory animals. Nonetheless, our knowledge of tonotopy at the apex of the cochlea remains incomplete in animals with low-frequency hearing, which is relevant to human speech. The results of our experiments on guinea pig, gerbil, and chinchilla cochleae, regardless of the sex of the animal, show that responses to sound differ at locations across the apex in a pattern consistent with previous studies of the base of the cochlea.SIGNIFICANCE STATEMENT:Tonotopy is an important property of the auditory system that has been shown to exist in many auditory centers. In fact, most auditory implants work on the assumption of its existence by assigning different frequencies to different stimulating electrodes based on their location. At the level of the basilar membrane in the cochlea, a tonotopic arrangement implies that high-frequency stimuli evoke largest displacements at the base, near the ossicles, and low-frequency sounds have their greatest effects at the apex. Although tonotopy has been confirmed at the base of the cochlea on live animals, at the apex of the cochlea, however, it has been less studied. Here we show that a tonotopic arrangement does exist at the apex of the cochlea.

Hearing consists of a delicate chain of events. Sound is first captured by an eardrum or similar organ which is set into vibrations, these vibrations must then be transmitted to sensory cells in a manner that opens mechanosensory channels generating an electrical signal. Studying this process is challenging. Auditory vibrations are in the nano- to picometer-scale and occur at fast temporal scales of milli to microseconds. Finally, most of this process occurs within the body of the animal where it is inaccessible to conventional measurement techniques. For instance, even in crickets, a century-old auditory model system, it is unclear how sound evoked vibrations are transmitted to sensory neurons. Here, we use optical coherence tomography (OCT) to measure how vibrations travel within the auditory organ of the western tree cricket (Oecanthus californicus). We also measure the reversal of this process as mechanosensory cells generate spontaneous oscillations and amplify sound-evoked vibrations. Most importantly, we found that while the mechanosensory neurons were not attached to the peripheral sound collecting structures, they were mechanically well-coupled through acoustic trachea. Thus, the acoustic trachea are not merely conduits for sound but also perform a mechanical function. Our results generate several insights into the similarities between insect and vertebrate hearing, and into the evolutionary history of auditory amplification.

Pigmented villonodular synovitis (PVNS) is a diffuse type tenosynovial giant cell tumor, which are benign but locally aggressive tumors presenting in joint, tendon sheath, and bursa synovium. This tumor most commonly occurs in the knee; it is rare in the head and neck region, where it most commonly arises in the temporomandibular joint (TMJ). We describe a case of PVNS occurring in the TMJ with extension into the external auditory canal and middle cranial fossa. The imaging characteristics, differential diagnosis, and treatment of PVNS is discussed.

Mammalian hearing depends on an amplification process involving prestin, a voltage-sensitive motor protein that enables cochlear outer hair cells (OHCs) to change length and generate force. However, it has been questioned whether this prestin-based somatic electromotility can operate fast enough in vivo to amplify cochlear vibrations at the high frequencies that mammals hear. In this study, we measured sound-evoked vibrations from within the living mouse cochlea and found that the top and bottom of the OHCs move in opposite directions at frequencies exceeding 20 kHz, consistent with fast somatic length changes. These motions are physiologically vulnerable, depend on prestin, and dominate the cochlea's vibratory response to high-frequency sound. This dominance was observed despite mechanisms that clearly low-pass filter the in vivo electromotile response. Low-pass filtering therefore does not critically limit the OHC's ability to move the organ of Corti on a cycle-by-cycle basis. Our data argue that electromotility serves as the primary high-frequency amplifying mechanism within the mammalian cochlea.

We describe optimization of a multi-window approach for improved resolution, side-lobe suppression, and phase sensitivity. Using the Hann window as a reference, we show that 10 windows are sufficient to achieve 43% resolution improvement, comparable side-lobe intensity, and 20% improvement in phase sensitivity.

The auditory system is particularly vulnerable to blast injury due to the ear's role as a highly sensitive pressure transducer. Over the past several decades, studies have used a variety of animal models and experimental procedures to recreate blast-induced acoustic trauma. Given the developing nature of this field and our incomplete understanding of molecular mechanisms underlying blast-related auditory disturbances, an updated discussion about these studies is warranted. Here, we comprehensively review well-established blast-related auditory pathology including tympanic membrane perforation and hair cell loss. In addition, we discuss important mechanistic studies that aim to bridge gaps in our current understanding of the molecular and microstructural events underlying blast-induced cochlear, auditory nerve, brainstem, and central auditory system damage. Key findings from the recent literature include the association between endolymphatic hydrops and cochlear synaptic loss, blast-induced neuroinflammatory markers in the peripheral and central auditory system, and therapeutic approaches targeting biochemical markers of blast injury. We conclude that blast is an extreme form of noise exposure. Blast waves produce cochlear damage that appears similar to, but more extreme than, the standard noise exposure protocols used in auditory research. However, experimental variations in studies of blast-induced acoustic trauma make it challenging to compare and interpret data across studies.

Sensory hair cells, the mechanoreceptors of the auditory and vestibular systems, harbor two specialized elaborations of the apical surface, the hair bundle and the cuticular plate. In contrast to the extensively studied mechanosensory hair bundle, the cuticular plate is not as well understood. It is believed to provide a rigid foundation for stereocilia motion, but specifics about its function, especially the significance of its integrity for long-term maintenance of hair cell mechanotransduction, are not known. We discovered that a hair cell protein called LIM only protein 7 (LMO7) is specifically localized in the cuticular plate and the cell junction. Lmo7 KO mice suffer multiple cuticular plate deficiencies, including reduced filamentous actin density and abnormal stereociliar rootlets. In addition to the cuticular plate defects, older Lmo7 KO mice develop abnormalities in inner hair cell stereocilia. Together, these defects affect cochlear tuning and sensitivity and give rise to late-onset progressive hearing loss., In contrast to the extensively studied mechanosensory hair bundle, the cuticular plate is not as well understood. In this study, authors describe the discovery of a hair cell protein called LIM only protein 7, which is localized in the cuticular plate and the cell junction and may play a role in age-related deafness.

Along with outer hair cell (OHC) somatic electromotility as the actuator of cochlear amplification, active hair bundle motility may be a complementary mechanism in the mammalian auditory system. Here, we searched the mouse cochlea for the presence of spontaneous bundle oscillations that have been observed in non-mammalian ears. In those systems, removal of the overlying membrane is necessary for spontaneous bundle oscillations to manifest. Thus, we used a genetic mouse model with a C1509G (cysteine-to-glycine) point mutation in the Tecta gene where the tectorial (TM) is lifted away from the OHC bundles, allowing us to explore whether unloaded bundles spontaneously oscillate. We used VOCTV in vivo to detect OHC length changes due to electromotility as a proxy for the spontaneous opening and closing of the mechanoelectrical transduction (MET) channels associated with bundle oscillation. In wild type mice with the TM attached to OHC bundles, we did find peaks in vibratory magnitude spectra. Such peaks were not observed in the mutants where the TM is detached from the OHC bundles. Statistical analysis of the time signals indicates that these peaks do not signify active oscillations. Rather, they are filtered responses of the sensitive wild type cochlea to weak background noise. We therefore conclude that, to the limits of our system (∼30 pm), there is no spontaneous mechanical activity that manifests as oscillations in OHC electromotility within the mouse cochlea, arguing that unloaded OHC bundles do not oscillate in vivo. This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam.

In this paper, we characterize establishment of joint attention in hearing parent–deaf child dyads and hearing parent–hearing child dyads. Deaf children were candidates for cochlear implantation who had not yet been implanted and who had no exposure to formal manual communication (e.g., American Sign Language). Because many parents whose deaf children go through early cochlear implant surgery do not themselves know a visual language, these dyads do not share a formal communication system based in a common sensory modality prior to the child’s implantation. Joint attention episodes were identified during free play between hearing parents and their hearing children ( $N = 4$ ) and hearing parents and their deaf children ( $N = 4$ ). Attentional episode types included successful parent-initiated joint attention, unsuccessful parent-initiated joint attention, passive attention, successful child-initiated joint attention, and unsuccessful child-initiated joint attention. Group differences emerged in both successful and unsuccessful parent-initiated attempts at joint attention, parent passive attention, and successful child-initiated attempts at joint attention based on proportion of time spent in each. These findings highlight joint attention as an indicator of early communicative efficacy in parent–child interaction for different child populations. We discuss the active role parents and children play in communication, regardless of their hearing status.

In mammals, sound is detected by mechanosensory hair cells that are activated in response to vibrations at frequency-dependent positions along the cochlear duct. We demonstrate that inner ear supporting cells provide a structural framework for transmitting sound energy through the cochlear partition. Humans and mice with mutations in GAS2, encoding a cytoskeletal regulatory protein, exhibit hearing loss due to disorganization and destabilization of microtubule bundles in pillar and Deiters' cells, two types of inner ear supporting cells with unique cytoskeletal specializations. Failure to maintain microtubule bundle integrity reduced supporting cell stiffness, which in turn altered cochlear micromechanics in Gas2 mutants. Vibratory responses to sound were measured in cochleae from live mice, revealing defects in the propagation and amplification of the traveling wave in Gas2 mutants. We propose that the microtubule bundling activity of GAS2 imparts supporting cells with mechanical properties for transmitting sound energy through the cochlea.

The mammalian cochlea achieves its remarkable sensitivity, frequency selectivity, and dynamic range by spatially segregating the different frequency components of sound via nonlinear processes that remain only partially understood. As a consequence of the wave-based nature of cochlear processing, the different frequency components of complex sounds interact spatially and nonlinearly, mutually suppressing one another as they propagate. Because understanding nonlinear wave interactions and their effects on hearing appears to require mathematically complex or computationally intensive models, theories of hearing that do not deal specifically with cochlear mechanics have often neglected the spatial nature of suppression phenomena. Here we describe a simple framework consisting of a nonlinear traveling-wave model whose spatial response properties can be estimated from basilar-membrane (BM) transfer functions. Without invoking jazzy details of organ-of-Corti mechanics, the model accounts well for the peculiar frequency-dependence of suppression found in two-tone suppression experiments. In particular, our analysis shows that near the peak of the traveling wave, the amplitude of the BM response depends primarily on the nonlinear properties of the traveling wave in more basal (high-frequency) regions. The proposed framework provides perhaps the simplest representation of cochlear signal processing that accounts for the spatially distributed effects of nonlinear wave propagation. Shifting the perspective from local filters to non-local, spatially distributed processes not only elucidates the character of cochlear signal processing, but also has important consequences for interpreting psychophysical experiments.

In the current study, we examine how hearing parents use multimodal cuing to establish joint attention with their hearing (N=9) or deaf (N=9) children during a free-play session. The deaf children were all candidates for cochlear implantation who had not yet been implanted, and each hearing child was age-matched to a deaf child. We coded parents' use of auditory, visual, and tactile cues, alone and in different combinations, during both successful and failed bids for children's attention. Although our findings revealed no clear quantitative differences in parents' use of multimodal cues as a function of child hearing status, secondary analyses revealed that hearing parents of deaf children used shorter utterances while initiating joint attention than did hearing parents of hearing children. Hearing parents of deaf children also touched their children twice as often throughout the play session than did hearing parents of hearing children. These findings demonstrate that parents differentially accommodate the specific needs of their hearing and deaf children in subtle ways to establish communicative intent.

Mammalian hearing sensitivity and frequency selectivity depend on a mechanical amplification process mediated by outer hair cells (OHCs). OHCs are situated within the organ of Corti atop the basilar membrane (BM), which supports sound-evoked traveling waves. It is well established that OHCs generate force to selectively amplify BM traveling waves where they peak, and that amplification accumulates from one location to the next over this narrow cochlear region. However, recent measurements demonstrate that traveling waves along the apical surface of the organ of Corti, the reticular lamina (RL), are amplified over a much broader region. Whether OHC forces accumulate along the length of the RL traveling wave to provide a form of “global” cochlear amplification is unclear. Here we examined the spatial accumulation of RL amplification. In mice of either sex, we used tones to suppress amplification from different cochlear regions and examined the effect on RL vibrations near and far from the traveling-wave peak. We found that although OHC forces amplify the entire RL traveling wave, amplification only accumulates near the peak, over the same region where BM motion is amplified. This contradicts the notion that RL motion is involved in a global amplification mechanism and reveals that the mechanical properties of the BM and organ of Corti tune how OHC forces accumulate spatially. Restricting the spatial buildup of amplification enhances frequency selectivity by sharpening the peaks of cochlear traveling waves and constrains the number of OHCs responsible for mechanical sensitivity at each location.SIGNIFICANCE STATEMENTOuter hair cells generate force to amplify traveling waves within the mammalian cochlea. This force generation is critical to the ability to detect and discriminate sounds. Nevertheless, how these forces couple to the motions of the surrounding structures and integrate along the cochlear length remains poorly understood. Here we demonstrate that outer hair cell-generated forces amplify traveling-wave motion on the organ of Corti throughout the wave's extent, but that these forces only accumulate longitudinally over a region near the wave's peak. The longitudinal coupling of outer hair cell-generated forces is therefore spatially tuned, likely by the mechanical properties of the basilar membrane and organ of Corti. Our findings provide new insight into the mechanical processes that underlie sensitive hearing.

Optical coherence tomography (OCT) has become an important tool for measuring the vibratory response of the living cochlea. It stands alone in its capacity to measure the intricate motion of the hearing organ through the surrounding otic capsule bone. Nevertheless, as an extension of phase-sensitive OCT, it is only capable of measuring motion along the optical axis. Hence, measurements are 1-D. To overcome this limitation and provide a measure of the 3-D vector of motion in the cochlea, we developed an OCT system with three sample arms in a single interferometer. Taking advantage of the long coherence length of our swept laser, we depth (frequency) encode the three channels. An algorithm to depth decode and coregister the three channels is followed by a coordinate transformation that takes the vibrational data from the experimental coordinate system to Cartesian or spherical polar coordinates. The system was validated using a piezo as a known vibrating element that could be positioned at various angles. The angular measurement on the piezo was shown to have an RMSE of ≤ 0.30° (5.2 mrad) with a standard deviation of the amplitude of ≤ 120 pm. Finally, we demonstrate the system for in vivo imaging by measuring the vector of motion over a volume image in the apex of the mouse cochlea.

One of the tenets of mammalian auditory physiology is that the frequency selectivity at the cochlear base decreases as a function of stimulus level. Changes in frequency selectivity have been shown to be accompanied by changes in response phases as a function of stimulus level. The existence of such nonlinear properties has been revealed by the analysis of either direct or indirect recordings of mechanical vibrations of the cochlea. Direct measurements of cochlear mechanical vibrations, however, have been carried out with success primarily in cochlear regions that are tuned to frequencies >7 kHz, but not in regions sensitive to lower frequencies. In this paper we continue to analyze recently published data from measurements of sound-induced vibrations at four locations near the apex of the intact guinea pig cochlea, in a region encompassing approximately 25% of its total length. Analysis of the responses at all locations reveal level-dependent phase properties that are rather different from those usually reported at the base of the cochlea of laboratory animals such as the chinchilla. Cochlear group delays, for example, increase or remain constant with increasing stimulus. Similarly, frequency selectivity at all the regions increases as a function of stimulus level.

There is indirect evidence that the mammalian cochlea in the low-frequency apical and the more commonly studied high-frequency basal regions function in fundamentally different ways. Here, we directly tested this hypothesis by measuring sound-induced vibrations of the organ of Corti (OoC) at three turns of the gerbil cochlea using volumetric optical coherence tomography vibrometry (VOCTV), an approach that permits noninvasive imaging through the bone. In the apical turn, there was little frequency selectivity, and the displacement-vs.-frequency curves had low-pass filter characteristics with a corner frequency of ~0.5–0.9 kHz. The vibratory magnitudes increased compressively with increasing stimulus intensity at all frequencies. In the middle turn, responses were similar except for a slight peak in the response at ~2.5 kHz. The gain was ~50 dB at the peak and 30–40 dB at lower frequencies. In the basal turn, responses were sharply tuned and compressively nonlinear, consistent with observations in the literature. These data demonstrated that there is a transition of the mechanical response of the OoC along the length of the cochlea such that frequency tuning is sharper in the base than in the apex. Because the responses are fundamentally different, it is not appropriate to simply frequency shift vibratory data measured at one cochlear location to predict the cochlear responses at other locations. Furthermore, this means that the number of hair cells stimulated by sound is larger for low-frequency stimuli and smaller for high-frequency stimuli for the same intensity level. Thus the mechanisms of central processing of sounds must vary with frequency. NEW & NOTEWORTHY A volumetric optical coherence tomography and vibrometry system was used to probe cochlear mechanics within the intact gerbil cochlea. We found a gradual transition of the mechanical response of the organ of Corti along the length of the cochlea such that tuning at the base is dramatically sharper than that at the apex. These data help to explain discrepancies in the literature regarding how the cochlea processes low-frequency sounds.

SUMMARY The stereociliary bundles of cochlear hair cells convert mechanical vibrations into the electrical signals required for auditory sensation. While the stiffness of the bundles strongly influences mechanotransduction, its influence on the vibratory response of the cochlear partition is unclear. To assess this, we measured cochlear vibrations in mutant mice with reduced bundle stiffness or with a tectorial membrane (TM) that is detached from the sensory epithelium. We found that reducing bundle stiffness decreased the high-frequency extent and sharpened the tuning of vibratory responses obtained postmortem. Detaching the TM further reduced the high-frequency extent of the vibrations but also lowered the partition’s resonant frequency. Together, these results demonstrate that the bundle’s stiffness and attachment to the TM contribute to passive longitudinal coupling in the cochlea. We conclude that the stereociliary bundles and TM interact to facilitate passive wave propagation to more apical locations, possibly enhancing active wave amplification in vivo., In Brief The mechanical properties of the cochlear partition determine its vibratory response to sound. Dewey et al. demonstrate that the outer hair cell stereociliary bundles’ stiffness and attachment to the tectorial membrane influence the partition’s passive vibratory response. The stereociliary bundles facilitate the propagation of cochlear waves to more apical regions., Graphical Abstract

KEY POINTS A popular conception of mammalian cochlear physiology is that tuned mechanical vibration of the basilar membrane defines the frequency response of the innervating auditory nerve fibres However, the data supporting these concepts come from vibratory measurements at cochlear locations tuned to high frequencies (>7 kHz). Here, we measured the travelling wave in regions of the guinea pig cochlea that respond to low frequencies ( 7 kHz, not in regions sensitive to lower frequencies where human speech is encoded. Here, we overcame historical technical limitations and non-invasively measured sound-induced vibrations at four locations distributed over the apical two turns of the guinea pig cochlea. In turn 3, the responses demonstrated low-pass filter characteristics. In turn 2, the responses were low-pass-like, in that they occasionally did have a slight peak near the corner frequency. The corner frequencies of the responses were tonotopically tuned and ranged from 384 to 668 Hz. Non-linear gain, or amplification of the vibrations in response to low-intensity stimuli, was found both below and above the corner frequencies. Post mortem, cochlear gain disappeared. The non-linear gain was typically 10-30 dB and was broad-band rather than sharply tuned. However, the gain did reach nearly 50 dB in turn 2 for higher stimulus frequencies, nearly the amount of gain found in basal cochlear regions. Thus, our data prove that mechanical responses do not match neural responses and that cochlear amplification does not appreciably sharpen frequency tuning for cochlear regions that respond to frequencies

A 3-D subnanometer vibrometry system based on Optical Coherence Tomography (OCT) is proposed in this work to measure the vector motion of a sample as well as the structure, which cannot be achieved by a current OCT based vibrometry system that measure 1-D vibrations only.

A principal tool for the visual inspection of the middle ear in the hearing clinic is the surgical stereo-microscope. We have developed a compact accessory for the surgical microscope that enables volumetric optical coherence tomography (OCT) imaging of the middle ear as well as functional vibratory imaging with subnanometer sensitivity. The sensitivity to vibration is achieved by careful engineering of the microscope attachment and frequency-domain processing. The microscope attachment integrates the entire OCT interferometer onto a custom aluminum base that mounts directly to the accessory area at the foot of most surgical microscopes. This approach is effective at removing high-frequency phase-noise, thus enabling near shot-noise limited sensitivity above ~2 kHz even though the OCT system is suspended above the patient by a boom arm. We analyze the vibratory response in the frequency domain, hence our ability to measure vibrations in the tympanic membrane and ossicles is near the shot-noise limit. As a demonstration of this system we have recorded in vivo volumetric images of a healthy human patient as well as the vibratory response at the tympanic membrane down to the hearing threshold. We also show that it is possible to use time averaging to drive the noise floor down below 2 pm which allowed us to make the first measure of distortion product otoacoustic emissions (DPOAE) using OCT. Finally, the system can easily be taken on and off of the surgical microscope and when in use does not impinge on the normal view through the surgical microscope.

We have developed a highly phase stable optical coherence tomography and vibrometry system that attaches directly to the accessory area of a surgical microscope common to both the otology clinic and operating room. Careful attention to minimizing sources of phase noise has enabled a system capable of measuring vibrations of the middle ear with a sensitivity of < 5 pm in an awake human patient. The system is shown to be capable of collecting a wide range of information on the morphology and function of the ear in live subjects, including frequency tuning curves below the hearing threshold, maps of tympanic membrane vibrational modes and thickness, and measures of distortion products due to the nonlinearities in the cochlear amplifier.

We describe an optical coherence tomography and vibrometry system designed for portable hand-held usage in the otology clinic on awake patients. The system provides clinically relevant point-of-care morphological imaging with 14-44 µm resolution and functional vibratory measures with sub-nanometer sensitivity. We evaluated various new approaches for extracting functional information including a multi-tone stimulus, a continuous chirp stimulus, and alternating air and bone stimulus. We also explored the vibratory response over an area of the tympanic membrane (TM) and generated TM thickness maps. Our results suggest that the system can provide real-time in vivo imaging and vibrometry of the ear and could prove useful for investigating otologic pathology in the clinic setting.

Neuroplastin (Nptn) is a member of the Ig superfamily and is expressed in two isoforms, Np55 and Np65. Np65 regulates synaptic transmission but the function of Np55 is unknown. In an N-ethyl-N-nitrosaurea mutagenesis screen, we have now generated a mouse line with an Nptn mutation that causes deafness. We show that Np55 is expressed in stereocilia of outer hair cells (OHCs) but not inner hair cells and affects interactions of stereocilia with the tectorial membrane. In vivo vibrometry demonstrates that cochlear amplification is absent in Nptn mutant mice, which is consistent with the failure of OHC stereocilia to maintain stable interactions with the tectorial membrane. Hair bundles show morphological defects as the mutant mice age and while mechanotransduction currents can be evoked in early postnatal hair cells, cochlea microphonics recordings indicate that mechanontransduction is affected as the mutant mice age. We thus conclude that differential splicing leads to functional diversification of Nptn, where Np55 is essential for OHC function, while Np65 is implicated in the regulation of synaptic function. SIGNIFICANCE STATEMENT Amplification of input sound signals, which is needed for the auditory sense organ to detect sounds over a wide intensity range, depends on mechanical coupling of outer hair cells to the tectorial membrane. The current study shows that neuroplastin, a member of the Ig superfamily, which has previously been linked to the regulation of synaptic plasticity, is critical to maintain a stable mechanical link of outer hair cells with the tectorial membrane. In vivo recordings demonstrate that neuroplastin is essential for sound amplification and that mutation in neuroplastin leads to auditory impairment in mice.

The exquisite sensitivity and frequency discrimination of mammalian hearing underlie the ability to understand complex speech in noise. This requires force generation by cochlear outer hair cells (OHCs) to amplify the basilar membrane traveling wave; however, it is unclear how amplification is achieved with sharp frequency tuning. Here we investigated the origin of tuning by measuring sound-induced 2-D vibrations within the mouse organ of Corti in vivo . Our goal was to determine the transfer function relating the radial shear between the structures that deflect the OHC bundle, the tectorial membrane and reticular lamina, to the transverse motion of the basilar membrane. We found that, after normalizing their responses to the vibration of the basilar membrane, the radial vibrations of the tectorial membrane and reticular lamina were tuned. The radial tuning peaked at a higher frequency than transverse basilar membrane tuning in the passive, postmortem condition. The radial tuning was similar in dead mice, indicating that this reflected passive, not active, mechanics. These findings were exaggerated in TectaC1509G/C1509G mice, where the tectorial membrane is detached from OHC stereocilia, arguing that the tuning of radial vibrations within the hair cell epithelium is distinct from tectorial membrane tuning. Together, these results reveal a passive, frequency-dependent contribution to cochlear filtering that is independent of basilar membrane filtering. These data argue that passive mechanics within the organ of Corti sharpen frequency selectivity by defining which OHCs enhance the vibration of the basilar membrane, thereby tuning the gain of cochlear amplification. SIGNIFICANCE STATEMENT Outer hair cells amplify the traveling wave within the mammalian cochlea. The resultant gain and frequency sharpening are necessary for speech discrimination, particularly in the presence of background noise. Here we measured the 2-D motion of the organ of Corti in mice and found that the structures that stimulate the outer hair cell stereocilia, the tectorial membrane and reticular lamina, were sharply tuned in the radial direction. Radial tuning was similar in dead mice and in mice lacking a tectorial membrane. This suggests that radial tuning comes from passive mechanics within the hair cell epithelium, and that these mechanics, at least in part, may tune the gain of cochlear amplification.

Functional neuroimaging can provide insight into the neurobiological factors that contribute to the variations in individual hearing outcomes following cochlear implantation. To date, measuring neural activity within the auditory cortex of cochlear implant (CI) recipients has been challenging, primarily because the use of traditional neuroimaging techniques is limited in people with CIs. Functional near-infrared spectroscopy (fNIRS) is an emerging technology that offers benefits in this population because it is non-invasive, compatible with CI devices, and not subject to electrical artifacts. However, there are important considerations to be made when using fNIRS to maximize the signal to noise ratio and to best identify meaningful cortical responses. This review considers these issues, the current data, and future directions for using fNIRS as a clinical application in individuals with CIs. This article is part of a Special Issue entitledAnnual Reviews 2016.

Hearing loss is the most common sensory disorder in the USA. The diagnosis of congenital hearing loss starts with newborn hearing screening, which is best performed with auditory brainstem evoked responses in order to avoid the risk of missing auditory neuropathy spectrum disorder. A careful history and physical exam can occasionally help reveal the etiology for congenital hearing loss. Imaging studies, either CT temporal bones or MRI of the internal auditory canals without gadolinium, and genetic testing, in particular for connexin 26, connexin 30, and Pendred syndrome, are the most useful diagnostic tests. Management of congenital hearing loss involves early fitting of amplification. Early cochlear implantation, preferably before 2 years of age, should be strongly considered for children with bilateral severe hearing loss.

Sensory hair cells, the mechanoreceptors of the auditory and vestibular system, harbor two specialized organelles, the hair bundle and the cuticular plate. Both subcellular structures have adapted to facilitate the remarkable sensitivity and speed of hair cell mechanotransduction. While the mechanosensory hair bundle is extensively studied, the molecules and mechanisms mediating the development and function of the cuticular plate are poorly understood. The cuticular plate is believed to provide a rigid foundation for stereociliar pivot movements, but specifics about its function, especially the significance of its integrity for long-term maintenance of hair cell mechanotransduction, are not known. In this study, we describe the discovery of a hair cell protein called LIM only protein 7 (LMO7). In the hair cell, LMO7 is specifically localized in the cuticular plate.Lmo7 KOmice suffer multiple deficiencies in the cuticular plate, including reduced filamentous actin density and abnormal length and distribution of stereociliar rootlets. In addition to the cuticular plate defects, olderLmo7 KOmice develop abnormalities in inner hair cell stereocilia. Together, these defects affect cochlear tuning and sensitivity and give rise to late-onset progressive hearing loss.

Traumatic noise causes hearing loss by damaging sensory hair cells and their auditory synapses. There are no treatments. Here, we investigated mice exposed to a blast wave approximating a roadside bomb. In vivo cochlear imaging revealed an increase in the volume of endolymph, the fluid within scala media, termed endolymphatic hydrops. Endolymphatic hydrops, hair cell loss, and cochlear synaptopathy were initiated by trauma to the mechanosensitive hair cell stereocilia and were K+-dependent. Increasing the osmolality of the adjacent perilymph treated endolymphatic hydrops and prevented synaptopathy, but did not prevent hair cell loss. Conversely, inducing endolymphatic hydrops in control mice by lowering perilymph osmolality caused cochlear synaptopathy that was glutamate-dependent, but did not cause hair cell loss. Thus, endolymphatic hydrops is a surrogate marker for synaptic bouton swelling after hair cells release excitotoxic levels of glutamate. Because osmotic stabilization prevents neural damage, it is a potential treatment to reduce hearing loss after noise exposure.

A highly-phase stable hand-held endoscopic system has been developed for optical coherence tomography and vibrometry. Designed to transit the ear canal to the middle ear space and peer through the round window, it is capable of imaging the vibratory function of the cochlear soft tissues with subnanometer scale sensitivity. A side-looking, 9 cm long rigid endoscope with a distal diameter of 1.2 mm, was able to fit within the round window niche and provide imaging access. The phase stability was achieved in part by fully integrating a Michelson interferometer into the hand-held device. Ex vivo imaging of a domestic pig demonstrated the system’s ability for functional vibratory imaging of the cochlea via the round window.

The mammalian cochlea has three rows of outer hair cells (OHCs) that amplify the basilar membrane (BM) traveling wave with high gain and exquisite sharpness. However, it is unclear why three rows of OHCs are needed to achieve this. We used a novel transgenic mouse with the diphtheria toxin receptor in Lgr5-positive cells (Lgr5DTR-EGFP/+ mouse) that allowed us to ablate the third row of OHCs and Deiters cells (D) in adulthood via DT injection, after normal cochlear function had developed. We then used volumetric optical coherence tomography (VOCTV) to investigate the impacts of this manipulation of cochlear amplification in the apical turn. As expected, Lgr5DTR-EGFP/+ control mice had sharply-tuned vibratory responses. However, Lgr5DTR-EGFP/+ mice had broad tuning with a 20 dB increase in vibratory thresholds. The Q10dB was ∼1 in Lgr5DTR-EGFP/+ mice, whereas it was ∼3 in control mice. The characteristic frequency was lower in Lgr5DTR-EGFP/+ mice compared to controls (7.5 vs. 9.0 kHz). The gain of cochlear amplification was substantially lower in Lgr5DTR-EGFP/+ mice compared to controls (22 vs. 50). In the post-mortem period, the vibratory responses in Lgr5DTR-EGFP/+ mice were identical to controls. Together, these results demonstrate the substantial importance of the third row of OHCs and Deiters cells to normal cochlear amplification.The mammalian cochlea has three rows of outer hair cells (OHCs) that amplify the basilar membrane (BM) traveling wave with high gain and exquisite sharpness. However, it is unclear why three rows of OHCs are needed to achieve this. We used a novel transgenic mouse with the diphtheria toxin receptor in Lgr5-positive cells (Lgr5DTR-EGFP/+ mouse) that allowed us to ablate the third row of OHCs and Deiters cells (D) in adulthood via DT injection, after normal cochlear function had developed. We then used volumetric optical coherence tomography (VOCTV) to investigate the impacts of this manipulation of cochlear amplification in the apical turn. As expected, Lgr5DTR-EGFP/+ control mice had sharply-tuned vibratory responses. However, Lgr5DTR-EGFP/+ mice had broad tuning with a 20 dB increase in vibratory thresholds. The Q10dB was ∼1 in Lgr5DTR-EGFP/+ mice, whereas it was ∼3 in control mice. The characteristic frequency was lower in Lgr5DTR-EGFP/+ mice compared to controls (7.5 vs. 9.0 kHz). The gain of cochlear ...