Journal of the Association for Research in Otolaryngology

High sensitivity and selectivity of hearing require active cochlea. The cochlear sensory epithelium, the organ of Corti, vibrates due to external and internal excitations. The external stimulation is acoustic pressures mediated by the scala fluids, while the internal excitation is generated by a type of sensory receptor cells (the outer hair cells) in response to the acoustical vibrations. The outer hair cells are cellular actuators that are responsible for cochlear amplification. The organ of Corti is highly structured for transmitting vibrations originating from acoustic pressure and active outer hair cell force to the inner hair cells that synapse on afferent nerves. Understanding how the organ of Corti vibrates due to acoustic pressure and outer hair cell force is critical for explaining cochlear function. In this study, excised cochlear turns were freshly isolated from young gerbils. The organ of Corti in the excised cochlea was subjected to mechanical and electrical stimulation that are analogous to acoustical and cellular stimulation in the natural cochlea. Organ of Corti vibrations including those of individual outer hair cells were measured using optical coherence tomography. Respective vibration patterns due to mechanical and electrical stimulation were characterized. Interactions between the two vibration patterns were investigated by applying the two forms of stimulation simultaneously. Our results show that the interactions could be either constructive or destructive, which implies that the outer hair cells can either amplify or suppress vibrations in the organ of Corti. We discuss a potential consequence of the two interaction modes for cochlear frequency tuning. Statement of SignificanceThe function of the mammalian cochlea is characterized by sharp tuning and high-level of amplification. Both tuning and amplification are achieved mechanically through the action of cellular actuators in the sensory epithelium. According to widely accepted theory, cochlear tuning is achieved by selectively amplifying acoustic vibrations. This study presents a set of data suggesting that the cochlear actuators can both amplify and suppress vibrations to enhance cochlear tuning. Presented results will explain why the actuator cells in the cochlea spend energy in the locations where there is no need for amplification.

HypothesisA custom spectral domain optical coherence tomography (SD-OCT) platform can be used for real-time guidance of a cochlear implant electrode array (EA). BackgroundWith current cochlear implant surgical techniques, placement of the EA is a blind maneuver in which the surgeon relies on tactile feedback as the EA advances through the cochlear lumen. Cochlear implant trauma is a leading factor for poor speech performance outcomes and loss of residual hearing following surgery. Optical coherence tomography (OCT) is a non-invasive imaging modality that provides real-time visualization of tissue microstructure at higher spatial resolutions compared to clinical CT and MRI. Already adopted as standard of care in ophthalmology, OCT has the potential to assist the surgeon in real-time visualization of the EA trajectory. Unlike commercial systems, our custom OCT system allows tailored wavelength, scanning geometry, and real-time processing, which are critical factors for navigating the compact anatomy of the facial recess to image the cochlea. MethodsA custom-built SD-OCT system was used to image cochlear microanatomy in mice and human cadaveric temporal bones. The OCT system was then used to guide a mock EA in human cadaveric temporal bones in real-time using individual B scans that were reviewed sequentially as the EA was being advanced through the round window. ResultsUsing our OCT system, high-resolution (< 5.0 m) images of cochlear microanatomy were obtained in both mice and cadaveric human temporal bones with an image sensitivity of [~]104 dB. Following cochleostomy in cadaveric temporal bones, real-time sequential OCT B-scans were used to reliably guide placement of the EA through the scala tympani. ConclusionOur custom-built SD-OCT platform can generate high-resolution real-time visualization and orientation of mammalian cochlear microanatomy that can be used to assist with real time guidance of a CI EA. This technology has the potential to serve as a real-time surgical image guidance tool to minimize EA trauma and further our understanding of human cochlear pathophysiology.

The rat vestibular system plays a critical role in anti-gravity responses such as the tail-lift reflex and the air-righting reflex. In a previous study in male rats, we obtained evidence that these two reflexes depend on the function of non-identical populations of vestibular sensory hair cells (HC). Here, we caused graded lesions in the vestibular system of female rats by exposing the animals to several different doses of an ototoxic chemical, 3,3-iminodipropionitrile (IDPN). After exposure, we assessed the anti-gravity responses of the rats and then assessed the loss of type I HC (HCI) and type II HC (HCII) in the central and peripheral regions of the crista, utricle and saccule. As expected, we recorded a dose-dependent loss of vestibular function and loss of HCs. The relationship between hair cell loss and functional loss was examined using non-linear models fitted by orthogonal distance regression. The results indicated that both the tail-lift reflex and the air-righting reflexes mostly depend on HCI function. However, a different dependency was found on the epithelium triggering the reflex: while the tail-lift response is sensitive to loss of crista and/or utricle HCIs, the air-righting response rather depends on utricular and/or saccular integrity.

The vestibular organs of birds are capable of regenerating sensory hair cells after ototoxic injury, but the regenerative ability of the mammalian vestibular organs is much more limited. The factors that inhibit regeneration in the mammalian inner ear are not known, but it has been proposed that the structure of filamentous actin cables at cell-cell junctions within the sensory epithelium may be an important regulatory influence. Junctional actin cables in the chick utricle are relatively thin, while those in mouse utricle are much thicker. These differences result in differing mechanical properties of the avian vs. mammalian inner ear, which may affect the potential for regenerative proliferation. The present study characterized injury-evoked changes in junctional actin cables in the utricles of mice and chicks. We found that the thickness of junctional cables in the chick utricle was not affected by ototoxic injury, but that injury to the mouse utricle led to the formation of many new junctional actin bands whose thickness was comparable to those in the chick utricle. Thicker actin bands persisted after injury, but were not necessarily associated with cellular junctions. In addition, the relative extent of supporting cell expansion in the injured chick utricle was larger than that in the mouse utricle, which may affect activation of Hippo/YAP signaling in both species. Together, these data point to important differences in actin cable plasticity in the avian vs. mammalian utricle that may partially account for their differing regenerative abilities.

To examine mechanisms responsible for vestibular afferent sensitivity to transient air conducted sounds (ACS) and inter-aural bone conducted vibration (BCV), we performed simultaneous measurements of stimulus-evoked vestibular compound action potentials (vCAPs), utricular macula or stapes velocity, and Vestibular Microphonics (VMs) in the anaesthetized guinea pig. For short duration punctate stimuli (<1ms), the vCAP increases magnitude in close proportion to macular velocity and temporal bone (ear-bar) acceleration, rather than other kinematic variables. For longer duration stimuli, the vCAP magnitude switches from acceleration sensitive to linear jerk sensitive. vCAP input-output (IO) functions suggest primary afferent response generation has the same origins for both BCV and ACS, with similar macular velocity thresholds and IO functions for both stimuli. Frequency tuning curves evoked by tone-burst stimuli also show the vCAP increases magnitude in proportion to macular velocity, while in contrast, the VM increases magnitude in proportion to macular displacement across the entire frequency bandwidth tested. The subset of vestibular afferent neurons responsible for synchronized firing and vCAPs make calyceal synaptic contacts with type I hair cells in the striolar region of the epithelium and have irregularly spaced inter-spike intervals at rest. Present results provide new insight into mechanical and neural mechanisms underlying synchronized action potentials in these sensitive afferents, with clinical relevance for understanding the activation and tuning of neurons responsible for driving rapid compensatory reflex responses. Significant statementCalyx-bearing afferents in the utricle have the remarkable ability to fire an action potential at a precise time following the onset of a transient stimulus and provide temporal information required for compensatory vestibular reflex circuits, but specifically how transient high-frequency stimuli lead to mechanical activation of hair cells and neural responses is poorly understood. Here, we dissect the relative contributions of mechanics, hair cell transduction, and action potential generation on short-latency responses to transient stimuli. Results provide a framework for the interpretation of synchronized vestibular afferent responses, with relevance to understanding origins of myogenic reflex responses commonly used in the clinic to assay vestibular function, and vestibular short latency potentials commonly used for vestibular phenotyping in rodents.

Inner ear hair cells are mechanoreceptors critical for hearing and balance. Damage to vestibular hair cells causes balance impairment, yet it is unclear whether hair cell loss correlates with vestibular dysfunction. In this study, we ablated hair cells in Pou4f3DTR/+ mice with diphtheria toxin (DT), and found a dose-dependent decrease in hair cell survival in both the macula and crista ampullaris, including loss of type I and II hair cells in the striolar/central and extrastriolar/peripheral regions. Responses to linear acceleration, measured by the translational vestibulo-ocular reflex (tVOR) and vestibular sensory evoked potential (VsEP), were intact with 25% or more hair cell survival in the macula, and diminished only when hair cell survival decreased further. By contrast, rotational vestibulo-ocular reflex (rVOR) responses were significantly reduced with [~]31% hair cell survival in the cristae. Further, single-unit recordings of vestibular afferents from cristae and maculae showed more irregular and reduced firing rates, but only those corresponding to cristae displayed reduced sensitivity to head rotation. Limited hair cell regeneration was observed in the extrastriolar/peripheral regions of both maculae and cristae 6 months post ablation, although no significant recovery of the VORs was observed. Thus, the adult mouse vestibular end organs display different degrees of redundancy, demonstrating robust responses to head rotation and linear acceleration despite loss of most hair cells.

Aging and noise over-exposure lead to complex mixtures of cochlear degradation that impair the structure and function of outer hair cells, inner hair cells (IHCs), and the cochlear nerve. However, IHC damage and cochlear synaptopathy (CS) remain pathologies "hidden" from the audiogram. This study aimed to identify and differentiate the physiological signatures of these two distinct pathologies using promising non-invasive assays: Envelope Following Responses (EFRs), Auditory Brainstem Response (ABRs), Wideband middle-ear reflexes (WB-MEMRs), and Distortion Product Otoacoustic Emissions (DPOAEs). We utilized chinchilla models of carboplatin-induced (CA) IHC damage (N = 4) and temporary threshold shift (TTS) noise-induced CS (N = 4) to compare the physiological signatures of each pathology. While both groups showed unchanged ABR thresholds two weeks after exposure, EFRs, ABR Wave V/I ratios, and MEMRs showed distinct effects of exposure. Despite non-elevated ABR-derived audiometric thresholds after exposure, both CA and TTS exposure resulted in severe in EFR "peakiness", particularly for sharp, short-duty-cycle stimuli and significant elevations in ABR Wave V/I ratios. However, these findings were less-pronounced in the TTS-exposed animals. WB-MEMR amplitudes were decreased with elevated thresholds in both groups; this effect was more pronounced in the TTS group. Opposite trends in DPOAE amplitudes indicated that while both IHC damage and CS result in similar suprathreshold temporal coding deficits, effects on outer-hair-cell integrity and auditory efferent physiology may differ between the two pathologies. Future work and novel diagnostics should aim to distinguish these specific cochlear pathologies in clinical populations, or at the very least consider their overlap. HighlightsO_LIA multi-metric diagnostic approach was used with chinchilla models of inner-hair-cell (IHC) damage and cochlear synaptopathy (CS). C_LIO_LIIHC damage and synaptopathy both cause suprathreshold deficits "hidden" from the audiogram. C_LIO_LIIHC damage results in more severe temporal envelope coding degradation than does synaptopathy. C_LIO_LIA combination of EFR "peakiness", ABR Wave V/I ratio, and Wideband Middle Ear Muscle Reflex (WB-MEMR) appear to be useful measures for profiling IHC damage and CS. C_LI

GABAergic neurons in the inferior colliculus (IC) play a crucial role in auditory processing by extracting specific features of sounds (Ono et al., 2005). The Gad67-GFP mouse model developed by Tamamaki et al. in 2003 on a Swiss background facilitates studying these neurons by using a green fluorescent protein that is expressed endogenously via the GAD67 promoter. Unfortunately, this mouse suffers from accelerated aging-related hearing loss, limiting its utility in studying the auditory system. Here, we report the results of an 8-generation backcross of this line onto CBA/CaJ mice, which produces mice with stable low-threshold hearing while retaining GFP expression in GAD+ neurons. Additionally, this study investigates mechanisms that underlie hearing loss in the Gad67-GFP mouse model by focusing specifically on cochlear hair cells (HCs) and ribbon synapses, which may contribute to both model-specific hearing loss and clinical disorders like presbycusis. Findings revealed the newly generated F1 mouse model that resulted from the Gad67-GFP x CBA/CaJ backcross maintained better hearing thresholds when compared to ABR data for Gad67 and Swiss mice and very closely resembled those of the CBA/CaJ mice, mirroring progression of presbycusis in humans. Additionally, all morphological changes observed in cochlear structure correlated to ABR thresholds. F1 mice continued maintained expression of the GAD67 promoter in the IC via immunostaining.

Auditory sensation is based in nanoscale vibration of the sensory tissue of the cochlea, the organ of Corti complex (OCC). Motion within the OCC is now observable due to optical coherence tomography. In the cochlear base, in response to sound stimulation, the region that includes the electro-motile outer hair cells (OHC) was observed to move with larger amplitude than the basilar membrane (BM) and surrounding regions. The intense motion is based in active cell mechanics, and the region was termed the "hotspot" (Cooper et al., 2018, Nature comm). In addition to this quantitative distinction, the hotspot moved qualitatively differently than the BM, in that its motion scaled nonlinearly with stimulus level at all frequencies, evincing sub-BF activity. Sub-BF activity enhances non-BF motion; thus the frequency tuning of the hotspot was reduced relative to the BM. Regions that did not exhibit sub-BF activity are here defined as the OCC "frame". By this definition the frame includes the BM, the medial and lateral OCC, and most significantly, the reticular lamina (RL). The frame concept groups the majority OCC as a structure that is largely shielded from sub-BF activity. This shielding, and how it is achieved, are key to the active frequency tuning of the cochlea. The observation that the RL does not move actively sub-BF indicates that hair cell stereocilia are not exposed to sub-BF activity. A complex difference analysis reveals the motion of the hotspot relative to the frame.

Age-related hearing loss is characterized by a progressive loss of threshold sensitivity, especially at high frequencies. There is increasing evidence that the loss of cilia in the inner and outer hair cells is the dominant cause of hearing loss. We present a framework for calculating the human auditory threshold based on a non-linear time-domain cochlear model that incorporates hair cell damage along the cochlear partition. We successfully predicted the audiogram measured prior to death by substituting the postmortem percentage of surviving hair cells, using data from Wu et al. (Wu et al., 2020). We also present an algorithm for estimating the percentage of hair cells from a measured audiogram. Comparison with the data from Wu et al. revealed that the algorithm accurately predicted the surviving inner hair cells along the entire cochlear partition and the outer hair cells at the basal part of the cochlea.

Vestibular schwannomas (VS) cause vestibular function loss by mechanisms still poorly understood. We evaluated the vestibulo-ocular reflex by the video-assisted Head Impulse Test (vHIT) in patients with planned tumour resection by a trans-labyrinthine approach. The vestibular sensory epithelia were collected and processed by immunofluorescent labelling for confocal microscopy analysis of sensory hair cell subtypes (type I, HCI, and type II, HCII), calyx endings of the pure-calyx afferents, and the calyceal junction normally found between HCI and the calyx (n=23). Comparing Normofunction and Hypofunction patients, we concluded that worse vestibular function associates with decreased HCI and HCII counts in the sensory epithelia and with increased proportion of damaged calyces. A decrease in the number of HCI and calyx endings of the pure-calyx afferents was recorded to associate with age increase. Partial least squares regression (PLSR) models indicated that VS and age had independent, additive effects on vestibular function. Correlation analyses indicated that lower vHIT gains associate with lower numbers of HCI and increased percentages of damaged calyces. These data support the hypothesis that the deleterious effect of VS on vestibular function is mediated, at least in part, by its damaging impact on the vestibular sensory epithelium. They also provide further evidence for the dependency of the vestibulo-ocular reflex on HCI function and for the calyceal junction pathology as a common response of the sensory epithelium to HC stress.

Vestibular dysfunction constitutes a major medical concern, and regeneration of hair cells (HC) is a primary target of gene therapy aimed at restoring vestibular functions. Thus far, therapeutic trials in animal models targeting vestibular loss associated with genetic diseases have yielded variable and partial results, and the functional identity and quantity of HCs required to restore minimal or normal vestibular function remain undefined. Indeed, direct comparisons between structural pathology and quantitative assessments of vestibular dysfunctions are lacking in humans and are rather limited in animal models, representing a significant gap in current knowledge. Here, we present an innovative methodology to bridge the gap between HC integrity and functional vestibular loss in individuals. Gradual vestibular deficits were induced through a dose-dependent ototoxic lesion, quantified with canal or utricular-specific vestibulo-ocular reflex tests, and were then correlated in all individuals with the loss of type I and type II HCs in different regions of ampulla and macula. Our findings reveal that the structure-function relationship is nonlinear, with lower bound of approximately 50% of HCs necessary to retain minimal vestibular function, and threshold exceeding 80% to preserve normal function, thus shedding light on population coding mechanisms for vestibular response. Our data further support the decisive role of type I, rather than type II, HC in the tested VOR functions.

The basilar membrane (BM) is connected to the reticular lamina (RL) through three rows of Y-shaped structures consisting of an outer hair cell (OHC) and a Deiters cell (DC) with a phalangeal process (PhP) that forms part of the RL mosaic surface. Morphological differences in the anatomy of the Y-shaped structures across the three OHC rows suggest differences in motion across the rows. Here we report OoC transverse motions measured across several radial locations for the gerbil basal region corresponding to ~45 kHz. Cross-sectional imaging and vibrometry measurements were made using a high-resolution (2.23 um axially in water) spectral-domain optical-coherence-tomography (SD-OCT) system. The stimuli were pure tones (2-63 kHz) at ear-canal sound pressure levels (SPLs) of 30-95 dB SPL in anesthetized gerbils (N=9) with healthy cochleae. We report displacements at the RL regions of OHC rows 1-3 (RL1-3), at the OHC-DC junctions of OHC rows 1-3 (OHC-DC-junction1-3), and at the arcuate zone, arcuate-pectinate junction, and pectinate zone of the BM (BMAZ, BMAPJ, and BMPZ, respectively). The in vivo BM displacements showed classic compressive nonlinearity and traveling-wave delays. The RL gain was similar to the BM gain at low frequencies (<20 kHz), but increased with frequency. Near the best frequency (BF), the RL gain was greater than the high-level BM gain by 40 {+/-}5 dB (mean{+/-}std), and had greater compressive nonlinearity. RL motion varied radially, and the RL3 gain was significantly greater than that of RL1 by 10 {+/-}1 dB (p<0.001). In contrast, the OHC-DC-junction gain varied little radially across OHCs. At low frequencies the OHC-DC-junction gain was constant across SPLs, and 14 {+/-} 3 dB greater than the BM gain. As the frequency increased, the OHC-DC-junction gain decreased to a level similar to the BM gain at BF. The RL2, 3 phase was advanced by 0.25-0.375 cycles relative to the BM phase at low frequencies, but the RL2, 3 phase lead decreased as the frequency increased, became similar to the BM phase at BF, and lagged behind the BM phase by 0.25-0.5 cycles above BF. The OHC-DC-junction phases were mostly similar to the BM phase at low frequencies, but became delayed relative to the BM as the frequency increased, typically by 0.25-0.5 cycles near BF and by up to 1 cycle above BF. Our results show the most detailed picture of motion around the three OHC rows yet published, indicating that RL motion varied radially. Surprisingly, there was little motion difference across the three OHC rows in the OHC-DC-junction region, indicating that the tops of the DCs move in unison. Our data show a rich array of OoC amplitude and phase variations that are not explained by current theories.

Because it is difficult to directly observe the morphology of the living cochlea, our ability to infer the mechanical functioning of the living ear has been limited. Nearly all of our knowledge about cochlear morphology comes from postmortem tissue that was fixed and processed using procedures that possibly distort the structures and fluid spaces of the organ of Corti. In this study, optical coherence tomography was employed to obtain in vivo and postmortem micron-scale volumetric images of the high-frequency hook region of the gerbil cochlea through the round-window membrane. The anatomical structures and fluid spaces of the organ of Corti were segmented and quantified in vivo and over a 90-minute postmortem period. The results show that some aspects of the organ of Corti are significantly altered over the course of death, such as the volumes of the fluid spaces, whereas the dimensions of other features change very little. We postulate that the fluid space of the outer tunnel and its surrounding tectal cells form a resonant structure that can affect the motion of the reticular lamina and thereby have a profound effect on outer-hair-cell transduction and thus cochlear amplification. In addition, the in vivo fluid pressure of the inner spiral sulcus is postulated to effectively inflate the connected sub-tectorial gap between the tectorial membrane and the reticular lamina. This gap height decreases after death, which is hypothesized to reduce and disrupt hair-cell transduction

Bilateral cochlear implant (CI) patients exhibit significant limitations in spatial hearing. Their ability to process interaural time differences (ITDs) is often impaired, while their ability to process interaural level differences (ILDs) remains comparatively good. Clinical studies aiming to identify the causes of these limitations are often plagued by confounds and ethical limitations. Recent behavioral work suggests that rats may be a good animal model for studying binaural hearing under neuroprosthetic stimulation, as rats develop excellent ITD sensitivity when provided with suitable CI stimulation. However, their ability to use ILDs has not yet been characterized. Objective of this study is to address this knowledge gap. Neontally deafened rats were bilaterally fitted with CIs, and trained to lateralize binaural stimuli according to ILD. Their behavioral ILD thresholds were measured at pulse rates from 50 to 2400 pps. CI rats exhibited high sensitivity to ILDs with thresholds of a few dB at all tested pulse rates. We conclude that early deafened rats develop good sensitivity, not only to ITDs but also to ILDs, if provided with appropriate CI stimulation. Their generally good performance, in line with expectations from other mammalian species, validates rats as an excellent model for research on binaural auditory prostheses.

IntroductionThe functional evaluation of auditory-nerve activity in spontaneous conditions has remained elusive in humans. In animals, the frequency analysis of the round-window electrical noise recorded by means of electrocochleography yields a frequency peak at around 900 to 1000 Hz, which has been proposed to reflect auditory-nerve spontaneous activity. Here, we studied the spectral components of the electrical noise obtained from cochlear implant electrocochleography in humans. MethodsWe recruited adult cochlear implant recipients from the Clinical Hospital of the Universidad de Chile, between the years 2021 and 2022. We used the AIM System from Advanced Bionics(R) to obtain single trial electrocochleography signals from the most apical electrode in cochlear implant users. We performed a protocol to study spontaneous activity and auditory responses to 0.5 and 2 kHz tones ResultsTwenty subjects including 12 females, with a mean age of 57.9 {+/-} 12.6 years (range between 36 and 78 years) were recruited. The electrical noise of the single trial cochlear implant electrocochleography signal yielded a reliable peak at 3.1 kHz in 55% of the cases (11 out of 20 subjects), while an oscillatory pattern that masked the spectrum was observed in seven cases. In the other two cases, the single-trial noise was not classifiable. Auditory stimulation at 0.5 kHz and 2.0 kHz did not change the amplitude of the 3.1 kHz frequency peak. ConclusionWe found two main types of noise patterns in the frequency analysis of the single-trial noise from cochlear implant electrocochleography, including a peak at 3.1 kHz that might reflect auditory-nerve spontaneous activity, while the oscillatory pattern probably corresponds to an artifact.

The mammalian hearing organ, the cochlea, contains an active amplifier to boost the vibrational response to low level sounds. Hallmarks of this active process are sharp location-dependent frequency tuning and compressive nonlinearity over a wide stimulus range. The amplifier relies on outer hair cell (OHC) generated forces driven in part by the endocochlear potential (EP), the ~ +80 mV potential maintained in scala media, generated by the stria vascularis. We transiently eliminated the EP in vivo by an intravenous injection of furosemide and measured the vibrations of different layers in the cochleas organ of Corti using optical coherence tomography. Distortion product otoacoustic emissions (DPOAE) were monitored at the same times. Following the injection, the vibrations of the basilar membrane lost the best frequency (BF) peak and showed broad tuning similar to a passive cochlea. The intra-organ of Corti vibrations measured in the region of the OHCs lost their BF peak and showed low-pass responses, but retained nonlinearity, indicating that OHC electromotility was still operational. Thus, while electromotility is presumably necessary for amplification, its presence is not sufficient for amplification. The BF peak recovered nearly fully within 2 hours, along with a non-monotonic DPOAE recovery that suggests that physical shifts in operating condition are a final step in the recovery process. SIGNIFICANCEThe endocochlear potential, the +80 mV potential difference across the fluid filled compartments of the cochlea, is essential for normal mechanoelectrical transduction, which leads to receptor potentials in the sensory hair cells when they vibrate in response to sound. Intracochlear vibrations are boosted tremendously by an active nonlinear feedback process that endows the cochlea with its healthy sensitivity and frequency resolution. When the endocochlear potential was reduced by an injection of furosemide, the basilar membrane vibrations resembled those of a passive cochlea, with broad tuning and linear scaling. The vibrations in the region of the outer hair cells also lost the tuned peak, but retained nonlinearity at frequencies below the peak, and these sub-BF responses recovered fairly rapidly. Vibration responses at the peak recovered nearly fully over 2 hours. The staged vibration recovery and a similarly staged DPOAE recovery suggests that physical shifts in operating condition are a final step in the process of cochlear recovery.

Cochlear implant (CI) surgery is one of the most utilized treatments for severe hearing loss. However, the effects of a successful scala tympani insertion on the mechanics of hearing are not yet fully understood. This paper presents a finite element (FE) model of the chinchilla inner ear for studying the interrelationship between the mechanical function and the insertion angle of a CI electrode. This FE model includes a three-chambered cochlea and full vestibular system, accomplished using -MRI and -CT scanning technology. This models first application found minimal loss of residual hearing due to insertion angle after CI surgery and indicates that it is a reliable and helpful tool for future application in CI design, surgical planning, and stimuli setup.

Cochlear implants (CIs) are by far the optimal option to partially restore hearing for the patients of sensorineural hearing impairment (HI) by electrically stimulating spiral ganglion neurons (SGNs). However, wide current spread from each electrode constitute an interface which restricts precision and quality of the electrical CIs. Recently, optogenetic stimulation of the cochlea has been proved as a more optimized approach via adeno-associated virus (AAV) carrying the gene encoding the light-sensitive channelrhodopsin-2. Here, we focus on summarizing recent work on stable and accurate ChR2 expression and compare the electrophysiological recording of optogenetic and acoustic stimulation in adult guinea pigs. Light stimulation generated auditory responses that was similar to that of acoustic stimulation. Moreover, normal hearing adult guinea pigs responded with a rise in amplitudes with increasing light intensity. In conclusion, optogenetic cochlear stimulation achieved good spectral selectivity of artificial sound encoding in a new adult rodent model, suggesting that the capabilities of optogenetics might be applied to improve cochlear implants in the future.

Human temporal bones suggest a steady decline of cochlear synapses with age and greater synapse loss in adults with a history of military or occupational noise exposure. However, there is currently no validated method of diagnosing this type of cochlear deafferentation in living humans. Animal models indicate that cochlear synaptopathy is associated with reduced auditory brainstem response (ABR) wave 1 amplitude and envelope following response (EFR) magnitude for a sinusoidally amplitude modulated (SAM) tone. However, translating the SAM EFR to humans is complicated because it is difficult to obtain this measurement in humans using the same modulation frequency that showed the strongest relationship with synaptopathy in mice (1000 Hz). Computational modeling suggests that EFR magnitude measured with a rectangular amplitude modulated (RAM) tone may be a more sensitive measure of synaptopathy than the SAM EFR. In addition, because synaptopathy likely co-occurs with outer hair cell dysfunction, a diagnostic assay for synaptopathy needs to be robust even when auditory thresholds are abnormal. This study compared the relative ability of the ABR, SAM EFR, and RAM EFR to predict synapse numbers in mice with a large range of auditory thresholds and degrees of synaptopathy. The results indicate that the RAM EFR modulated at 1000 Hz is the single best predictor of synapse number when there is a broad loss of synapses across frequency, while combining RAM EFR and ABR further improves synapse prediction. In contrast, focal synaptopathy is best predicted by ABR wave 1 amplitude. Significance StatementThis study assessed the relative ability of two auditory evoked potentials to identify cochlear synaptopathy, a type of cochlear deafferentation that occurs with age and noise exposure, in mice. Performance of these measures in the presence of outer hair cell (OHC) damage was also evaluated because synaptopathy is expected to often co-occur with OHC dysfunction. Concrete recommendations of measurements to use for non-invasive diagnosis of synaptopathy in humans are provided. This represents a significant advance toward diagnosis of a condition that is thought to have a high prevalence in humans. The ability to identify individuals with cochlear synaptopathy is vital for furthering our understanding of how this auditory deficit impairs auditory perception and the future development of treatment options.