Microanatomy of the human tunnel of Corti structures and cochlear partition-tonotopic variations and transcellular signaling.

Auditory sensitivity and frequency resolution depend on the optimal transfer of sound-induced vibrations from the basilar membrane (BM) to the inner hair cells (IHCs), the principal auditory receptors. There remains a paucity of information on how this is accomplished along the frequency range in the human cochlea. Most of the current knowledge is derived either from animal experiments or human tissue processed after death, offering limited structural preservation and optical resolution. In our study, we analyzed the cytoarchitecture of the human cochlear partition at different frequency locations using high-resolution microscopy of uniquely preserved normal human tissue. The results may have clinical implications and increase our understanding of how frequency-dependent acoustic vibrations are carried to human IHCs. A 1-micron-thick plastic-embedded section (mid-modiolar) from a normal human cochlea uniquely preserved at lateral skull base surgery was analyzed using light and transmission electron microscopy (LM, TEM). Frequency locations were estimated using synchrotron radiation phase-contrast imaging (SR-PCI). Archival human tissue prepared for scanning electron microscopy (SEM) and super-resolution structured illumination microscopy (SR-SIM) were also used and compared in this study. Microscopy demonstrated great variations in the dimension and architecture of the human cochlear partition along the frequency range. Pillar cell geometry was closely regulated and depended on the reticular lamina slope and tympanic lip angle. A type II collagen-expressing lamina extended medially from the tympanic lip under the inner sulcus, here named "accessory basilar membrane." It was linked to the tympanic lip and inner pillar foot, and it may contribute to the overall compliance of the cochlear partition. Based on the findings, we speculate on the remarkable microanatomic inflections and geometric relationships which relay different sound-induced vibrations to the IHCs, including their relevance for the evolution of human speech reception and electric stimulation with auditory implants. The inner pillar transcellular microtubule/actin system's role of directly converting vibration energy to the IHC cuticular plate and ciliary bundle is highlighted.

Research on sound quality prediction of vehicle interior noise using the human-ear physiological model.

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

Frequency-Selective, Multi-Channel, Self-Powered Artificial Basilar Membrane Sensor with a Spiral Shape and 24 Critical Bands Inspired by the Human Cochlea.

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

Regional differences in cochlear nonlinearity across the basal organ of Corti of gerbil: Regional differences in cochlear nonlinearity.

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 a previous study (Cooper et al., 2018), the region that includes the electro-motile outer hair cells (OHC) and Deiters cells (DC) was observed to move with larger amplitude than the basilar membrane (BM) and surrounding regions and was termed the "hotspot." 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 OHC/DC region was reduced relative to the BM. In this work we further explore the motion of the gerbil basal OCC and find that regions that lack significant sub-BF activity include the BM, the medial and lateral OCC, and the reticular lamina (RL) region. The observation that the RL region does not move actively sub-BF (already observed in Cho and Puria 2022), suggests that hair cell stereocilia are not exposed to sub-BF activity in the cochlear base. The observation that the lateral and RL regions move approximately linearly sub-BF indicates that linear forces dominate non-linear OHC-based forces on these components at sub-BF frequencies. A complex difference analysis was performed to reveal the internal motion of the OHC/DC region and showed that amplitude structure and phase shifts in the directly measured OHC/DC motion emerge due to the internal OHC/DC motion destructively interfering with BM motion.

Asymmetric vibrations in the organ of Corti by outer hair cells measured from excised gerbil cochlea.

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

Measurement of the Mechanical Deformation of Organ of Corti in a Model of Acute Endolymphatic Hydrops / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Endolymphatic hydrops has been considered as an important histologic substrate of Meniere's disease. A permanent displacement of basilar membrane (BM) by increased endolymphatic pressure has been thought to be an explanation for hearing change. Direct observation of histological sections of temporal bones, however, suggested that stereocilia and tectorial membrane decoupling is more associated with pressure induced by mechanical deformation of the organ of Corti rather than with the displacement of BM. METERIALS AND METHOD: 26 cochleae from 13 female pigmented ginea pigs were harvested. One cochlea per each animal was injected with artificial perilymph. The other one was used as control. After fixation, followed by embedding and mid-modiolar sectionning, specimens were observed with a microscope. Morphometric parameters of each row and turn of the organ of Corti were measured and quantified. RESULTS: The average area and height of the organ of Corti were significantly smaller in the apical turn of the experimental group (p<0.05). The lengths of outer hair cell and Deiters cell in the apical turn were also significantly reduced in the experimental group (p<0.05). The angle between the outer hair cell and Deiters cell was smaller in the apex and in the 3rd turn of the experimental group (p<0.05). CONCLUSION: Results show that compression and deformation of the organ of Corti, especially in the apical turn, is a prominent feature in the acute endolymphatic hydrops model. We suggest that the deformation of organ of Corti is the primary cause of hydrops that induce the decoupling of tectorial membrane and stereocilia rather than the displacement of BM.

Mass and Stiffness Impact on the Middle Ear and the Cochlear Partition

Mass and stiffness affect on the peculiar characteristics of transmission of the middle ear and the distinctive behavior of the cochlear mechanics. Applying the principle of the mass and stiffness, the band-pass characteristic transfer function of the middle ear has been explained. The greatest transfer function of the middle ear, approximately 24-29 dB, is observed at 1-2 kHz in both cat and human species. However, at lower frequencies, the transfer function was disturbed by the stiffness of the middle ear primarily due to middle ear cavity. At higher frequencies, the transfer function was disturbed by the stiffness of the middle ear primarily due to middle ear bones. Several examples, such as an acoustic reflex, otitis media, and otosclerosis are discussed. For understanding the traveling wave of the basilar membrane, different place tuning at certain stimulus frequencies, contrastingly shaped basilar membrane to the cochlear duct, and the structural and physical characteristics of the whole cochlear partition were reviewed in terms of changing width, mass, and stiffness from the base to apex. Being about ten times wider, more massive, and one hundredfold stiffer at the base than the apex, the nature of the cochlear partition to absorb high-frequency energy changes in fluid pressure declines toward the apex. Consequently, at the base of the cochlea, high frequencies stimuli are decoded while low frequencies stimuli are decoded at the apex of the cochlea. Due to these characteristics of the cochlear partition, the direction of the traveling wave was also proved to be in the fashion of base-to-apex always.

Relationship of distortion product in cochlea with cochlear activity revealed by laser interferometry / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the relationship of distortion product in cochlea with cochlear activity and hearing.@*METHOD@#Time variances of distortion product of basilar membrane vibration in vitro guineapig cochlea were observed by laser interferometry.@*RESULT@#Within half hour after a cochlea was isolated from a guineapig, distortion product accompanied with two-tone inhibition in cochlea, can be observed. As time passed, distortion product and two-tone inhibition effect disappeared at the same time. After that, the membrane contiune vibrating in response to the sound stimulus, but the vibration amplitude decreased obviously and continued decreasing until it disappeared completely.@*CONCLUSION@#Distortion product in cochlea is a symbol of cochlear activity which makes the membrane respond in large amplitude vibration to sound stimulus and exhibit two-tone inhibition. The former makes the hearing highly sensitive to sound stimulus, the later makes the hearing perform information abstract well.

A mechanical simulation model of the basilar membrane of the cochlea / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a mechanical simulation model for studying the relationship between the characteristic frequency and feature location of the basilar membrane of the cochlea.</p><p><b>METHODS</b>Macro-mechanical methods were used to simplify the details of the model. With simulation tools, the basilar membrane vibration frequency characteristics were analyzed based on the box model.</p><p><b>RESULTS</b>The basilar membrane had obvious frequency-selective properties, and the basilar membrane from the stapes was sensitive to high frequencies while the farther membrane was sensitive to low frequencies.</p><p><b>CONCLUSION</b>The frequency characteristics of the basilar membrane of the cochlea is mainly a result of the longitudinal variations of the geometric dimensions and material properties and is not related with other structures within the cochlea corti.</p>

Apoptosis Progression in the Hair Cells in the Organ of Corti of GJB2 Conditional Knockout Mice

OBJECTIVES: Apoptosis may play an important role in the mechanism underlying the GJB2 gene conditional knockout (cCx26) mice cochlear cell death. The objective of this study was to explore the the damage mode of the outer hair cells (OHCs) and its real time point of apoptosis and provide information to further explore the role of apoptosis in the happening of hearing loss in cCx26 mice. METHODS: Cochleae from mice at various developmental stages (P8, P12, and P21) were dissected out and first used to be observed under the scanning electron microscope (SEM). Basilar membranes from mice at P8, P14, P18, and P21 were stained by fluorescein isothiocyanate-conjugated phalloidin and propidium iodide (PI) and examined under confocal microscope. RESULTS: The loss of OHCs of cCx26 knockout mice was first set between P12 and P21 under SEM. Whole mount phalloidin and PI staining revealed that obvious apoptotic appearance of the OHCs surface morphology was observed at P18. CONCLUSION: Typical apoptotic morphology was found in the OHCs in the organ of Corti of the cCx26 mice at P18. This may provide information to further study the role of apoptosis in the occurrence of hearing loss of cCx26 mice.

Mechanisms and Treatment of Blast Induced Hearing Loss

The main objective of this study is to provide an overview of the basic mechanisms of blast induced hearing loss and review pharmacological treatments or interventions that can reduce or inhibit blast induced hearing loss. The mechanisms of blast induced hearing loss have been studied in experimental animal models mimicking features of damage or injury seen in human. Blast induced hearing loss is characterized by perforation and rupture of the tympanic membrane, ossicular damage, basilar membrane damage, inner and outer hair cell loss, rupture of round window, changes in chemical components of cochlear fluid, vasospasm, ischemia, oxidative stress, excitotoxicity, hematoma, and hemorrhage in both animals and humans. These histopathological consequences of blast exposure can induce hearing loss, tinnitus, dizziness, and headache. The pharmacological approaches to block or inhibit some of the auditory pathological consequences caused by blast exposure have been developed with antioxidant drugs such as 2,4-disulfonyl alpha-phenyl tertiary butyl nitrone (HXY-059, now called HPN-07) and N-acetylcysteine (NAC). A combination of antioxidant drugs (HPN-07 and NAC) was administered to reduce blast induced cochlear damage and hearing loss. The combination of the antioxidant drugs can prevent or treat blast induced hearing loss by reducing damage to the mechanical and neural component of the auditory system. Although information of the underlying mechanisms and treatment of blast induced hearing loss are provided, further and deep research should be achieved due to the limited and controversial knowledge.

Mechanisms and Treatment of Blast Induced Hearing Loss

The main objective of this study is to provide an overview of the basic mechanisms of blast induced hearing loss and review pharmacological treatments or interventions that can reduce or inhibit blast induced hearing loss. The mechanisms of blast induced hearing loss have been studied in experimental animal models mimicking features of damage or injury seen in human. Blast induced hearing loss is characterized by perforation and rupture of the tympanic membrane, ossicular damage, basilar membrane damage, inner and outer hair cell loss, rupture of round window, changes in chemical components of cochlear fluid, vasospasm, ischemia, oxidative stress, excitotoxicity, hematoma, and hemorrhage in both animals and humans. These histopathological consequences of blast exposure can induce hearing loss, tinnitus, dizziness, and headache. The pharmacological approaches to block or inhibit some of the auditory pathological consequences caused by blast exposure have been developed with antioxidant drugs such as 2,4-disulfonyl alpha-phenyl tertiary butyl nitrone (HXY-059, now called HPN-07) and N-acetylcysteine (NAC). A combination of antioxidant drugs (HPN-07 and NAC) was administered to reduce blast induced cochlear damage and hearing loss. The combination of the antioxidant drugs can prevent or treat blast induced hearing loss by reducing damage to the mechanical and neural component of the auditory system. Although information of the underlying mechanisms and treatment of blast induced hearing loss are provided, further and deep research should be achieved due to the limited and controversial knowledge.

Aneurismas de bifurcación basilar: vía óptico-carotídea / Basilar bifurcacion aneurysms: via optic-carotid

Los aneurismas de la bifurcación basilar abordados a través de una vía pterional pueden ser accesados a través del espacio óptico-carotídeo. Pueden considerarse otros espacios de acceso hacia la bifurcación basilar: el retrocarotídeo medial, el lateral y el de la supra-bifurcación. En este artículo presento la técnica de la vía a través del espacio óptico-carotídeo, formado por estructuras neuro-vasculares importantes.

Diagnostic Value of Cochlear Hydrops Analysis Masking Procedure in Meniere's Disease / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The diagnosis of Meniere's disease is based on audiological test and clinical symptoms. Cochlear Hydrops Analysis Masking Procedure (CHAMP) was introduced as a test for detecting changes in physical characteristics of basilar membrane by hydrops of endolympahtic system. The aim of this study is to evaluate the diagnostic value and usefulness of CHAMP tests for detection of endolymphatic hydrops. SUBJECTS AND METHOD: This study was performed on 11 cases of Meniere's disease and 10 cases of vestibular neuritis who visited ENT outpatient clinic and 25 cases of normal healthy volunteers. We defined the positive value as being less than 0.3 ms in latency delay (0.5 kHz HPN-click alone) and less than 0.95 nV in compound amplitude ratio (click alone 0.5 kHz HPN/ click alone) regardless of age or sex. RESULTS: There were significant latency delays in the Meniere's disease group compared with the vestibular neuritis and normal control group. The amplitude ratio gave significant differences between the Meniere's disease group and the normal group but there were no differences between the Meniere's disease group and the vestibular neuritis group. Without assuming the test failure, the sensitivity and specificity of latency delay was 81% and 100%, respectively, and the sensitivity and specificity of amplitude ratio was 100% and 84%, respectively. In 8 of 54 cases (14.8%), we couldn't get interpretable wave. CONCLUSION: CHAMP test is a clinically useful method that can detect endolymphatic hydrops and it can be used as an objective test for the diagonosis of Meniere's disease.

Construction of recombinant adenoviral vector to coexpress human neurotrophin3 and EGFP gene and its conduction efficiency to rat cochlea in vitro / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To construct an adenoviral vector that codes for both human NT3 and EGFP, to confirm the transduction efficiency in rat cochlear cultures and to assess the protection of NT3 on SGNs survival.@*METHOD@#PAdeasy-1 and pAdTrack CMV were used to constructed Ad/NT3 adenovirus and then to transfer postnatal day 3 rat cochlear cultures. The transduction efficiency was determined by microscope observation. The amounts of SGNs were counted to evaluated protection of Ad/NT3 on SGNs survival.@*RESULT@#EGFP positive cells were observed in all cochlear turns. There was approximately 49% in outer sulcus cells and 27% in the interdental cells; less than 2% of the hair cells and SGN. The amounts of SGN of treated Ad/NT3 adenovirus are more than cochlea SGN only Ad/EGFP adenovirus after cultured for 15 days.@*CONCLUSION@#Ad/NT3 adenovirus could transduce EGFP and NT3 in large number of supporting cells, but few hair cells or SGNs. The putative release of NT3 from these supporting cells could enhance cell survival and promote neurite outgrowth from SGNs.

The Effect of Acetylcholine on the Potassium Currents and Length of Outer Hair Cell / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Inner hair cells (IHCs) of the organ of Corti change the external sound stimulus into the electrical signal and transmit this signal to the auditory cortex through afferent nerve fibers. Outer hair cells (OHCs) control the sound transmission function of IHC. OHCs respond with a somatic shape change to alterations in their membrane potential and this electromotile response is believed to provide mechanical feedback to the basilar membrane. Efferent nerve fibers which arise from the superior olivary nucleus in the midbrain and transmit to OHCs through medial olivocochlear bundle use acetylcholine (ACh) as a neurotransmitter. The cholinergic response of OHCs' alpha-9 nicotinic ACh receptor increase the Ca2+ influx, which control OHCs' electromotility by changing a membrane potential. In this research, the effect of ACh on the K+ current in OHC of guinea pig was studied, and the change of OHC length by ACh was studied. MATERIALS AND METHODS: Using the extracted OHC from a guinea pig potassium currents induced by ACh were recorded using the whole-cell patch clamp technique. The change of OHC length when ACh was applied was observed. RESULTS: 1) ACh increases voltage-dependent K+ current in OHC. 2) In the condition, which Ca2+-dependent K+ current is blocked by removing Ca2+ from intra-cellular fluid, ACh has no effect on K+ current in OHC. 3) ACh increases OHC length. CONCLUSION: These experimental results show that ACh from the medial olivocochlear efferent system regulates mobility of OHC, increases the Ca2+-dependent K+ currents in OHC.

The Latency of Distortion Product Otoacoustic Emissions in Normal Ears / 대한이비인후과학회지

Distortion-Product Otoacoustic Emissions(DPOAEs) are thought to be generated from the cochlear outer hair cells. DPOAEs can be measured in the external ear canal twofold:amplitude and latency. However, most DPOAE studies deal with amplitude aspects. If DPOAE latency is related to the progression of the traveling wave along the basilar membrane, it may also reflect the cochlear function. The purpose of this study was to investigate if the latency measurement could be used as a clinical test of hearing. For this purpose, DPOAE latency measures were examined as a function of frequency from 1 to 8 kHz in 38 normal ears from 19 adults(7 females and 12 males). Results showed that the latency decreased as frequency increased up to 6 kHz. Test/retest reliability was relatively high in 4-6 kHz and the lowest at 1 kHz. There was no gender effect for all test frequencies. The results suggest that the measurement of DPOAE latency has a clinical potential, but more data be obtained before it can be clinically used.

Apical Turn Vibratory Response Changes Following Cisplatin Application in the Living Guinea Pig Cochlea / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Cisplatin (cis-diamminodichloroplatinum) exercises its ototoxic effect by damaging hair cells of the inner ear. The effect of cisplatin on the vibratory response of the inner ear was investigated in the apical turn of the cochlea in 11 living guinea pigs. MATERIALS AND METHODS: The exposed turn was sealed and fluid coupled to the objective lens of a slit confocal microscope. Individual cells were identified with the microscope and the vibration was measured with a confocal heterodyne interferometer. The vibration was made in response to tones applied to the ear canalat at selected locations such as the reticular lamina (Hensen cells and outer hair cells), and the basilar membrane adjacent to the outer Hensen cell edge. Vibration measurements were made before and after intravenous injections of cisplatin (16 mg/kg). RESULTS: The drug effect took place approximately 35 minutes after administering cisplatin. The vibration amplitude changes produced by cisplatin were not reversible with time. At the level of the reticular lamina, cisplatin reduced the vibration amplitude at almost all frequencies. However, these effects were small. In contrast to the reticular lamina response, at the basilar membrane, the vibration amplitude increased following cisplatin application. CONCLUSION: These experiments show that damage to the hair cells in the apical turn of the cochlea leads to an increase in the basilar membrane vibration. These observations support the concept of negative Feedback in the apical turn of the cochlea.

Expression of Tonicity-Responsive Enhancer Binding Protein (TonEBP) in the Rat Cochlea: An Immunohistochemical Study / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The inner ear is an organ used for hearing and balance. For its normal function, the inner ear fluid homeostasis is required. There has been controversy over the regulatory mechanisms of maintaining inner ear fluid balance, and they have not yet been clearly defined. TonEBP is the protein that binds tonicity-responsive enhancer elements in the osmoprotective gene, which elevates the compatible osmolytes, which in turn induces cell survival in hypertonic condition. The aim of this study was to elucidate if there is an osmoregulatory mechanism in cochlea. Material and Method: The localization of TonEBP in the cochlea of male Sprague-Dawley rats was studied by immunohistochemistry with an anti rabbit polyclonal anti-rat TonEBP antibody. RESULTS: TonEBP was expressed at outer hair cells, Deiter cells, spiral ligaments, sprial limbus connective tissues, and epithelial lining of basilar membrane facing scala tympani. CONCLUSION: TonEBP in cochlea is one of the proteins involved in elucidating cell survival in changed tonicity during inner ear homeostasis.

Frequency tuning of mechanical responses in the mammalian cochlea

The search for mechanisms responsible for the high sensitivity and sharp frequency tuning of first-order auditory neurons has produced surprising results. The cochlea, the mammalian auditory receptor, responds to acoustic stimuli with a sharply frequency tuned, nonlinear vibration that enhances low level stimuli, but generates appreciable distortion. This highly sensitive mechanical response is achieved by an electro-mechanical feedback process in which outer hair cells reinforce cochlear motion at low stimulus intensities