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Sensorineural deafness is caused by the loss of peripheral neural input to the auditory nerve, which may result from peripheral neural degeneration and/or a loss of inner hair cells. Provided spiral ganglion cells and their central processes are patent, cochlear implants can be used to electrically stimulate the auditory nerve to facilitate hearing in the deaf or severely hard-of-hearing. Neural degeneration is a crucial impediment to the functional success of a cochlear implant. The present, first-of-its-kind two-dimensional finite-element model investigates how the depletion of neural tissues might alter the electrically induced transmembrane potential of spiral ganglion neurons. The study suggests that even as little as 10% of neural tissue degeneration could lead to a disproportionate change in the stimulation profile of the auditory nerve. This result implies that apart from encapsulation layer formation around the cochlear implant electrode, tissue degeneration could also be an essential reason for the apparent inconsistencies in the functionality of cochlear implants.

As a by-product of nonlinear amplification in the cochlea, the inner ear emits sound waves in response to two tones with different frequencies. These sound waves are measurable in the ear canal as distortion-product otoacoustic emissions (DPOAEs). DPOAEs putatively consist of two components emerging at different locations in the cochlea. Wave interference between the two components limits the accuracy of DPOAEs as a noninvasive measure of cochlear function. Using short stimulus pulses instead of continuous stimuli, the two DPOAE components can be separated in the time domain due to their different latencies. The present work utilizes a nonlinear hydrodynamic cochlea model to simulate short-pulse DPOAEs in the time domain. When adding irregularities to the mechanical parameters of the model, the simulated DPOAE signals show two distinguishable components and long-lasting beat tones, similar to band-pass filtered experimental data from normal-hearing human subjects. The model results suggest that the beat tones can occur solely due to interference of the coherent-reflection component with the fading nonlinear-distortion component.

Distortion-product otoacoustic emissions (DPOAEs) arise in the cochlea in response to two tones with frequencies f1 and f2 and mainly consist of two components, a nonlinear-distortion and a coherent-reflection component. Wave interference between these components limits the accuracy of DPOAEs when evaluating the function of the cochlea with conventional continuous stimulus tones. Here, DPOAE components are separated in the time domain from DPOAE signals elicited with short stimulus pulses. The extracted nonlinear-distortion components are used to derive estimated distortion-product thresholds (EDPTs) from semi-logarithmic input-output (I/O) functions for 20 normal-hearing and 21 hearing-impaired subjects. I/O functions were measured with frequency-specific stimulus levels at eight frequencies f2 = 1,…, 8 kHz (f2/f1 = 1.2). For comparison, DPOAEs were also elicited with continuous primary tones. Both acquisition paradigms yielded EDPTs, which significantly correlated with behavioral thresholds (p

The amplitudes of distortion-product otoacoustic emissions (DPOAEs) may abruptly decrease even though the stimulus level is relatively high. These notches observed in the DPOAE input/output functions or distortion-product grams have been hypothesized to be due to destructive interference between wavelets generated by distributed sources of the nonlinear-distortion component of DPOAEs. In this paper, simulations with a smooth cochlear model and its analytical solution support the hypothesis that destructive interference between individual wavelets may lead to the amplitude notches and explain the cause for onset and offset amplitude overshoots in the DPOAE signal measured for intensity pairs in the notches.

Cochlear implantation leads to many structural changes within the cochlea which can impair residual hearing. In patients with preserved low-frequency hearing, a delayed hearing loss can occur weeks-to-years post-implantation. We explore whether stiffening of the basilar membrane (BM) may be a contributory factor in an animal model. Our objective is to map changes in morphology and Young's modulus of basal and apical areas of the BM after cochlear implantation, using quantitative nanomechanical atomic force microscopy (QNM-AFM) after cochlear implant surgery. Cochlear implantation was undertaken in the guinea pig, and the BM was harvested at four time-points: 1 day, 14 days, 28 days and 84 days post-implantation for QNM-AFM analysis. Auditory brainstem response thresholds were determined prior to implantation and termination. BM tissue showed altered morphology and a progressive increase in Young's modulus, mainly in the apex, over time after implantation. BM tissue from the cochlear base demonstrated areas of extreme stiffness which are likely due to micro-calcification on the BM. In conclusion, stiffening of the BM after cochlear implantation occurs over time, even at sites far apical to a cochlear implant.

Distortion product otoacoustic emissions (DPOAEs) are evoked by two stimulus tones with frequency f 1 and f 2 of ratio f 2 / f 1 in the range between approximately 1.05 and 1.4. This study theoretically and experimentally analyzes the cubic 2 f 1 − f 2 DPOAE for different stimulus levels of one of the tones while the other is constant. Simulations for f 2 / f 1 of 1.2 and moderate stimulus levels (30–70 dB sound pressure level) indicate that cubic distortion products are generated along a relatively large length of the basilar membrane, the extent of which increases with stimulus level. However, apical from the place of maximum nonlinear force, the wavelets generated by these distributed sources mutually cancel. Therefore, although the spatial extent of the primary DPOAE sources broadens with increasing stimulus level (up to 1.5 oct), the basilar-membrane region contributing to the DPOAE signal is relatively narrow (0.6 oct) and level independent. The observed dependence of DPOAE amplitude on stimulus level can be well-approximated by a point source at the basilar-membrane place where the largest distortion product (maximum of the nonlinear force) is generated. Onset and offset of the DPOAE signal may contain amplitude overshoots (complexities), which are in most cases asymmetrical. Two-tone suppression was identified as the main cause of these onset and offset complexities. DPOAE measurements in two normal-hearing subjects support the level dependence of the steady-state DPOAE amplitude and the asymmetry in the onset and offset responses predicted by the theoretical analysis.

When referred to baseline measures, serial monitoring of pure-tone behavioral thresholds and distortion-product otoacoustic emissions (DPOAEs) can be used to detect the progression of cochlear damage. Semi-logarithmic DPOAE input-output (I/O) functions enable the computation of estimated distortion-product thresholds (EDPTs) by means of linear regression, a metric that provides a quantitative estimate of hearing loss due to cochlear-amplifier degradation. DPOAE wave interference and a suboptimal choice of stimulus levels limit the accuracy of EDPTs. This work identifies the test-retest reliability of EDPTs derived from short-pulse DPOAE level maps (EDPTLM), a method that circumvents limitations associated with both wave interference and suboptimal choice of stimulus levels. The test-retest reliability was compared to that of EDPTs derived from semi-logarithmic I/O functions (EDPTI/O) and that of behavioral thresholds acquired with pure-tone audiometry (PTA) and modified Bekesy tracking audiometry (TA) to provide a foundation for identifying and interpreting significant threshold shifts. The DPOAE-based auditory thresholds (EDPTLM and EDPTI/O) and behavioral thresholds (PTA and TA) were recorded seven times within three months at 14 frequencies with f2 = 1-14 kHz in 20 ears from ten subjects with normal hearing (4PTA0.5-4kHz < 20 dB HL). To obtain EDPTLM, short-pulse DPOAEs were recorded using 21 L1,L2 pairs. Reconstruction of DPOAE growth behavior as a function of L1 and L2 using nonlinear curve fitting enabled the derivation of EDPTLM for each frequency. Test-retest reliability was determined using three different approaches: 1) centered thresholds, 2) average threshold differences, and 3) average absolute threshold differences, between each possible test session (N = 21). Test-retest reliability based on centered thresholds and average threshold differences showed no statistically significant difference between EDPTLM, EDPTI/O, PTA, and TA for the pooled analysis incorporating all stimulus frequencies. Average absolute threshold differences presented small but significant differences in test-retest reliability with median values of 3.00 dB for PTA, 3.20 dB for TA, 3.34 dB for EDPTLM, and 3.51 dB for EDPTI/O. A considerable frequency dependence of test-retest reliability was found; namely, the highest test-retest reliability was for EDPTLM at f2 = 11 - 14 kHz. Otherwise, at lower frequencies, the highest test-retest reliability was for TA at f2 =1 - 2 kHz. Overall, the test-retest reliability of EDPTLM was better than that of EDPTI/O and was similar to that for behavioral thresholds. Hence, deriving EDPTLM from individual level maps is a promising and sensitive method for objectively monitoring the state of the cochlea. Furthermore, the detection of an equidirectional threshold change at a single frequency in both EDPTLM and TA might allow reducing the threshold shift as indication of a follow-up examination from the clinical standard of 10 dB down to 5 dB. This stricter indicator might be beneficial when monitoring cochlear damage, for example ototoxicity, in the presence of (remnant) cochlear amplification at baseline.

Distortion-product otoacoustic emissions (DPOAEs) arise as byproduct of nonlinear amplification in the cochlea in response to two stimulus tones of different frequencies. They are assumed to comprise mainly two components, a nonlinear-distortion component and a coherent-reflection component, which may cause wave interference in recordings with conventional, continuous stimulus tones, hampering the accuracy of DPOAEs when evaluating cochlear function. Here, DPOAEs are recorded with short stimulus pulses enabling the separation of the two source components in the time domain. Comparison with conventional stimulation endorses the importance of reliable source separation when using DPOAEs in clinical audiometry or research.

Aim: To obtain direct evidence for the cochlear travelling wave in humans by performing electrocochleography from within the cochlea in subjects implanted with an auditory prosthesis. Background: Sound induces a travelling wave that propagates along the basilar membrane, exhibiting cochleotopic tuning with a frequency-dependent phase delay. To date, evoked potentials and psychophysical experiments have supported the presence of the travelling wave in humans, but direct measurements have not been made. Methods: Electrical potentials in response to rarefaction and condensation acoustic tone bursts were recorded from multiple sites along the human cochlea, directly from a cochlear implant electrode during, and immediately after, its insertion. These recordings were made from individuals with residual hearing. Results: Electrocochleography was recorded from 11 intracochlear electrodes in 7 ears from 6 subjects, with detectable responses on all electrodes in 5 ears. Cochleotopic tuning and frequency-dependent phase delay of the cochlear microphonic were demonstrated. The response latencies were slightly shorter than those anticipated which we attribute to the subjects' hearing loss. Conclusions: Direct evidence for the travelling wave was observed. Electrocochleography from cochlear implant electrodes provides site-specific information on hair cell and neural function of the cochlea with potential diagnostic value.

Distortion-product otoacoustic emissions (DPOAEs) emerge when presenting two primary tones with different frequencies f1 and f2 to the cochlea and are commonly used in diagnosis and research to evaluate the functional state of the cochlea. Optimal primary-tone stimulus levels accounting for the different level dependencies of the traveling-wave amplitudes of the two primary tones near the f2-tonotopic place on the basilar membrane are often used to maximize DPOAE amplitudes. However, parameters defining the optimal levels can be affected by wave interference between the nonlinear-distortion and coherent-reflection components of the DPOAE. Here, the components were separated in the time domain using a pulsed stimulus paradigm and optimal levels determined. Based on the amplitude dependence of the nonlinear-distortion components on primary-tone stimulus levels, level parameters yielding maximum DPOAE amplitudes were derived for six normal-hearing adults and compared to data recorded with continuous two-tone stimulation. The level parameters resulting from analysis of the nonlinear-distortion components show dependence on stimulus frequency and small standard deviations. DPOAE input/output functions derived for optimal levels exhibit larger slopes, wider dynamic range and less variability across subjects than those derived for conventional stimulus and analysis conditions, potentially increasing their reliability and sensitivity for assessing cochlea function.

Distortion-product otoacoustic emissions (DPOAEs) are presumed to consist mainly of two components, a nonlinear-distortion component and a coherent-reflection component. Wave interference between these two components reduces the accuracy of DPOAEs when used to evaluate cochlear function. Here, short tone pulses are utilized to record DPOAE signals in normal-hearing subjects. DPOAE components are extracted from recordings at discrete frequencies using two different techniques in the time domain. The extracted DPOAE components are compared to recordings obtained with conventional, continuous primary tones.

The basis of the extraordinary sensitivity and frequency selectivity of the mammalian cochlea is an electromechanical feedback system that amplifies the deflection of the hair cell stereocilia. Electromechanical force is generated by the soma of the outer hair cell and acts against viscous forces. These forces are expected to be particularly large in the narrow subtectorial space between the reticular lamina and the overlying tectorial membrane. Fundamental aspects of this amplifying process are not fully understood. Three main questions are addressed in this chapter. First, given capacitive and inertial characteristics of cellular and acellular cochlear components, how is the electromechanical force coupled to the stereocilia locally, radially, and longitudinally, with correct phase to produce gain rather than attenuation? Second, how is temporal fidelity achieved in the presence of high gain? Third, what is the evidence for power amplification rather than just amplitude amplification? This chapter presents modern experimental approaches that are addressing these issues. Presented in a conceptual framework of experiment and theory, three approaches are highlighted: (1) combined pressure and voltage measurements near the organ of Corti, (2) vibration measurements at the reticular lamina and tectorial membrane, and (3) mechanical and electrokinetic properties of the tectorial membrane. The experimental evidence supports the thesis that average power gain in the region of maximum amplitude response and coupling through the tectorial membrane are both crucial for shaping the frequency response of the cochlear amplifier and, therefore, of stereocilia deflection.

Coupling of somatic electromechanical force from the outer hair cells (OHCs) into the organ of Corti is investigated by measuring transverse vibration patterns of the organ of Cori and tectorial membrane (TM) in response to intracochlear electrical stimulation. Measurement places at the organ of Corti extend from the inner sulcus cells to Hensen’s cells and at the lower (and upper) surface of the TM from the inner sulcus to the OHC region. These locations are in the neighborhood of where electromechanical force is coupled into (1) the mechanoelectrical transducers of the stereocilia and (2) fluids of the organ of Corti. Experiments are conducted in the first, second, and third cochlear turns of an in vitro preparation of the adult guinea pig cochlea. Vibration measurements are made at functionally relevant stimulus frequencies (0.48–68 kHz) and response amplitudes (

Distortion product otoacoustic emissions (DPOAEs) measured as vibration of the human eardrum have been successfully used to estimate hearing threshold. The estimates have proved more accurate than similar methods using sound-pressure DPOAEs. Nevertheless, the estimation accuracy of the new technique might have been influenced by endogenous noise, such as heart beat, breathing and swallowing. Here, we investigate in an animal model to what extent the accuracy of the threshold estimation technique using velocity-DPOAEs might be improved by reducing noise sources. Velocity-DPOAE I/O functions were measured in normal and hearing-impaired anaesthetized guinea pigs. Hearing loss was either conductive or induced by furosemide injection. The estimated distortion product threshold (EDPT) obtained by extrapolation of the I/O function to the abscissa was found to linearly correlate with the compound action potential threshold at the f(2) frequency, provided that furosemide data were excluded. The standard deviation of the linear regression fit was 6 dB as opposed to 8 dB in humans, suggesting that this accuracy should be achievable in humans with appropriate improvement of signal-to-noise ratio. For the furosemide animals, the CAP threshold relative to the regression line provided an estimate of the functional loss of the inner hair cell system. For mechanical losses in the middle ear and/or cochlear amplifier, DPOAEs measured as velocity of the umbo promise an accuracy of hearing threshold estimation comparable to classical audiometry.

It has previously not been possible to measure eardrum vibration of human subjects in the region of auditory threshold. It is proposed that such measurements should provide information about the status of the mechanical amplifier in the cochlea. It is this amplifier that is responsible for our extraordinary hearing sensitivity. Here, we present results from a laser Doppler vibrometer that we designed to noninvasively probe cochlear mechanics near auditory threshold. This device enables picometer-sized vibration measurements of the human eardrum in vivo . With this sensitivity, we found the eardrum frequency response to be linear down to at least a 20-dB sound pressure level (SPL). Nonlinear cochlear amplification was evaluated with the cubic distortion product of the otoacoustic emissions (DPOAEs) in response to sound stimulation with two tones. DPOAEs originate from mechanical nonlinearity in the cochlea. For stimulus frequencies, f 1 and f 2 , with f 2 / f 1 = 1.2 and f 2 = 4–9.5 kHz, and intensities L 1 and L 2 , with L 1 = 0.4 L 2 + 39 dB and L 2 = 20–65 dB SPL, the DPOAE displacement amplitudes were no more than 8 pm across subjects ( n = 20), with hearing loss up to 16 dB. DPOAE vibration was nonlinearly dependent on vibration at f 2 . The dependence allowed the hearing threshold to be estimated objectively with high accuracy; the standard deviation of the threshold estimate was only 8.6 dB SPL. This device promises to be a powerful tool for differentially characterizing the mechanical condition of the cochlea and middle ear with high accuracy.

INTRODUCTION Active middle-ear implants with floating-mass transducer (FMT) technology are used to treat mild-to-severe sensorineural hearing losses. The standard surgical approach for incus vibroplasty is a mastoidectomy and a posterior tympanotomy, crimping the FMT to the long incus process. An alternative fixation side with less surgical trauma might be the short incus process and incus body.The aim of this study was to develop and test a short incus process coupling device for its functional properties in temporal bone preparations and clinical practice. MATERIALS AND METHODS An extended antrotomy and a posterior tympanotomy were performed in 10 fresh human temporal bones. As a control for normal middle-ear function, the tympanic membrane was stimulated acoustically, and the vibration of the stapes footplate was measured using laser Doppler vibrometry. FMT-induced vibration responses of the stapes were then measured for standard attachment at the long process and for 2 types of couplers designed for attachment at the short process of the incus (SP1 and SP2 coupler). Additionally, the functional outcome in 2 patients provided with an SP2 coupler was assessed postoperatively at 2 weeks, 3 months, and then 11 months, using pure-tone audiometry, auditory thresholds for frequency-modulated (warble) tones, vibroplasty thresholds, and speech audiometry in quiet and noise. RESULTS For the SP2 coupler, velocity-amplitude responses in temporal-bone preparations showed generally similar mean amplitudes as compared with the standard coupling of the FMT to the long process but with clearly increased mean amplitudes between 0.7 and 1.5 kHz and with reduced interindividual variation between 0.5 and 3 kHz. The clinical data of 2 patients with mild-to-severe sensory hearing loss showed good vibroplasty thresholds and convincing results for speech audiometry in quiet (Freiburger monosyllables at 65 dB SPL, 23 ± 31% unaided versus 83 ± 4% aided) and noise (Hochmair-Schulz-Moser-test at 65 dB SPL at 10 dB SNR, 32 ± 45% unaided and 42 ± 29% aided). CONCLUSION The attachment of the FMT to the short incus process with the SP2 coupler leads to good mechanical and functional coupling in an experimental setup and clinical practice.

The stereocilia of the cochlear inner hair cells (IHCs) transduce vibrations into the sensory receptor current. Until now, mechanisms for deflecting these stereocilia have not been identified experimentally. Here, we identify a mechanism by using the electromechanical properties of the soma of the outer hair cell to produce an intracochlear, mechanical force stimulus. It is known that the soma of this cell generates mechanical force in response to a change of its transmembrane potential. In the present experiments, the force was induced by intracochlear electrical stimulation at frequencies that covered the entire functionally relevant range of 50 kHz. Vibration responses were measured in the transverse direction with a laser Doppler vibrometer. For frequencies up to approximately 3 kHz in the first three turns of the guinea-pig cochlea, the apical surface of the IHC and the opposing surface of the tectorial membrane were found to vibrate with similar amplitudes but opposite phases. At high frequencies, there was little relative motion between these surfaces in the transverse direction. The counterphasic motion up to approximately 3 kHz results in a pulsatile motion of the fluid surrounding the stereocilia of the IHCs. Based on physical principles of fluid flow between narrowly spaced elastic plates, we show that radial fluid motion is amplified relative to transverse membrane motion and that the radial motion is capable of bending the stereocilia. In conclusion, for frequencies up to at least 3 kHz, there appears to be direct fluid coupling between outer hair cells and IHCs.

Electromechanical force derived from the soma of the outer hair cell has long been postulated as the basis of the exquisite sensitivity of the cochlea. The problem with this postulate is that the electrical source and mechanical load for the electromechanical outer hair cell might be severely attenuated and phase-shifted by the electrical impedance of the cell and the mechanical impedance of the organ of Corti, respectively. Until now, it has not been possible to experimentally derive the high-frequency electrically induced force at the reticular lamina when the cells are embedded within the organ of Corti. In the study reported here, we succeeded in determining the frequency spectrum of the force up to 50 kHz. This was achieved by measuring both the electrically induced velocity and the mechanical impedance at different radial positions on the reticular lamina without tectorial membrane and with clamped basilar membrane. Velocity was measured with a laser interferometer and impedance, with a magnetically driven atomic force cantilever. The electromechanical force, normalized to the electric current density, exhibited a broad amplitude maximum at 7–20 kHz with a quality factor, Q 3dB , of 0.6 - 0.8. The displacement response was independent of frequency up to 10–20 kHz. The force response compensates for the viscoelastic impedance of the organ of Corti, extending the amplitude response of the organ to high frequencies. It is proposed that the electrical phase response of the cell is compensated with Zwislocki's original mechanism of a parallel resonance in the tectorial membrane–stereocilia complex.

Measurement of contralateral suppression or ipsilateral adaptation of DPOAE due to the medial olivocochlear reflex (MOCR) in humans has so far been complicated by interference between the two major contributors to a DPOAE signal, namely, the nonlinear and the reflection-source components. For instance, while the MOCR has been shown to act inhibitory to the cochlear amplifier, a considerable share of the measured responses has been reported to be of the excitatory type (e.g. 22% for contralateral adaptation in [11]), and it has been shown that the magnitudes of ipsilateral adaptation as well as contralateral suppression depend on the precise frequency choice relative to the position of dips in the DPOAE fine structure [3, 8]. To separate MOCR effects on both source components, we developed a paradigm consisting of five short f2 pulses presented during a 0.35 s on-period of the f1 primary within blocks of 1.35 s length. The responses at f1 and f2 were cancelled using the primary-tone phase variation techniq...

Cochlear outer hair cells (OHCs) are responsible for the exquisite sensitivity, dynamic range, and frequency-resolving capacity of the mammalian hearing organ. These unique cells respond to an electrical stimulus with a cycle-by-cycle change in cell length that is mediated by molecular motors in the cells' basolateral membrane. Recent work identified prestin, a protein with similarity to pendrin-related anion transporters, as the OHC motor molecule. Here we show that heterologously expressed prestin from rat OHCs (rprestin) exhibits reciprocal electromechanical properties as known for the OHC motor protein. Upon electrical stimulation in the microchamber configuration, rprestin generates mechanical force with constant amplitude and phase up to a stimulus frequency of at least 20 kHz. Mechanical stimulation of rprestin in excised outside-out patches shifts the voltage dependence of the nonlinear capacitance characterizing the electrical properties of the molecule. The results indicate that rprestin is a molecular motor that displays reciprocal electromechanical properties over the entire frequency range relevant for mammalian hearing.

Hearing loss is most often the result of hair-cell degeneration due to genetic abnormalities or ototoxic and traumatic insults. In the postembryonic and adult mammalian auditory sensory epithelium, the organ of Corti, no hair-cell regeneration has ever been observed. However, nonmammalian hair-cell epithelia are capable of regenerating sensory hair cells as a consequence of nonsensory supporting-cell proliferation. The supporting cells of the organ of Corti are highly specialized, terminally differentiated cell types that apparently are incapable of proliferation. At the molecular level terminally differentiated cells have been shown to express high levels of cell-cycle inhibitors, in particular, cyclin-dependent kinase inhibitors [Parker, S. B., et al . (1995) Science 267, 1024–1027], which are thought to be responsible for preventing these cells from reentering the cell cycle. Here we report that the cyclin-dependent kinase inhibitor p27 Kip1 is selectively expressed in the supporting-cell population of the organ of Corti. Effects of p27 Kip1 -gene disruption include ongoing cell proliferation in postnatal and adult mouse organ of Corti at time points well after mitosis normally has ceased during embryonic development. This suggests that release from p27 Kip1 -induced cell-cycle arrest is sufficient to allow supporting-cell proliferation to occur. This finding may provide an important pathway for inducing hair-cell regeneration in the mammalian hearing organ.

A complete battery of audiometric methods is required for the differential diagnosis of different hearing disabilities (including puretone audiometry, impedance, stapes reflex, speech audiometry, brainstam evoked response audiometry, otoacoustic emissions, etc.). In many cases, a comprehensive diagnosis is not possible. Here we describe a new technique based on a laser-Doppler vibrometer that has the potential for non-invasive diagnosis not only middle ear disease but also cochlear pathologies. Disturbance of cochlear function can be ascertained because the input impedance of the cochlea acts as a mechanical load on the middle ear and therefore influences motion of the umbo. In the present study vibration of the umbo and eardrum were measured with a commercially available laser-Doppler vibrometer coupled directly into a standard surgical microscope. The use of the microscope allowed non-invasive measurements of vibrations without having to introduce reflecting material onto the tympanic membrane. Sound pressure was measured with a calibrated probe microphone placed near the tympanic membrane. The displacement response and the specific acoustic impedance of the umbo were calculated from the velocity and sound pressure measured. For normal hearing subjects, the amplitude of the umbo's displacement for frequencies from 0.1 kHz to 1 kHz was 1 nm at 60 dB SPL and decreased with a slope of 6 dB/octave for frequencies between 1 and 5 kHz. A strong correlation was found between the specific acoustic impedance of the umbo and hearing thresholds for hearing-impaired subjects (having otosclerosis or sensorineural hearing losses). The frequency response of the umbo proved to be a means for evaluating the function of both the middle ear and the cochlea under pathological conditions. The measurement technique described is also suitable for intraoperative investigation of the frequency response of the opened middle ear, as well as for the in situ frequency response of partial and total ossicular replacement prostheses.

To test the hypothesis that the tip-links of hair-cell stereocilia are essential for mechanoelectrical transduction, tip-links of isolated outer hair cells (OHCs) of the guinea-pig cochlea were eliminated with a proteolytic enzyme, elastase, and the influence on the receptor potential measured with the whole-cell patch-clamp technique. Within 45 s of immersion of the hair bundle in 20 IU/ml elastase, the receptor potential in response to direct deflection of the hair bundle was irreversibly abolished. The electrical input impedance of the cell remained unchanged, implying that the channels of the basolateral membrane were not affected by elastase. The effect of elastase on the receptor potential was comparable to changes seen after mechanically induced hair-bundle damage. As a further control, a putative transduction-channel blocker, dihydrostreptomycin (68 microM), which does not affect tip-links, was applied to the hair bundle. Although the receptor potential was also blocked by dihydrostreptomycin, the effect was reversible. The results suggest that tip-links are required for mechanoelectrical transduction of mammalian OHCs.

Sound-induced displacement responses in the plane of the organ of Corti were studied in the apical turn in the isolated temporal-bone preparation of the guinea-pig cochlea. Swept sinusoidal sound stimuli (100-500 Hz) were delivered closed-field to the external auditory meatus. The surface of the organ of Corti was continuously monitored using a CCD video camera. Displacement responses in the plane of the organ of Corti were determined by analyzing the change of the location of the cells (pixel-by-pixel) within the visual field of the microscope. Displacement responses followed the stimulus amplitude and were observable at Hensen's cells, three rows of outer hair cells and inner hair cells. The most prominent displacement responses were over the outer hair cells; the maximum amplitude was 0.6-1.7 microns at 100 dB SPL. Tuned displacement responses were found; the Q10 dB was 1.3 +/- 0.6. The best frequency was tonotopically organized, decreasing toward the apex with a space constant of 0.4-0.9 mm/oct. The motion was directed either strial-apically or strial-basally in a frequency dependent manner. With the aid of laser interferometric measurements of the transverse displacement, it was concluded that sound stimulation does not induce slow DC motion in the organ of Corti for the isolated temporal-bone preparation.

Estimation of the function of the cochlea in human is possible only by deduction from indirect measurements, which may be subjective or objective. Therefore, for basic research as well as diagnostic purposes, it is important to develop methods to deduce and analyse error sources of cochlear‐state estimation techniques. Here, we present a model of technical and physiologic error sources contributing to the estimation accuracy of hearing threshold and the state of the cochlear amplifier and deduce from measurements of human that the estimated standard deviation can be considerably below 6 dB. Experimental evidence is drawn from two partly independent objective estimation techniques for the auditory signal chain based on measurements of otoacoustic emissions.

Laserinterferometrically measured distortion product otoacoustic emissions provide a means of assessing hearing threshold with high accuracy. It is shown that together with the measurement of the vibration response of the tympanic membrane to sound, a model of the middle ear can be fitted automatically to a forward and a reverse transfer function. The model can be used to estimate the complete transfer function of the middle ear and thus provides a potential means for differential diagnosis of middle- and inner-ear pathologies.

The outer hair cells are responsible for the exquisite sensitivity, frequency selectivity and dynamic range of the cochlea. These cells are part of a mechanical feedback system involving the basilar membrane and tectorial membrane. Transverse displacement of the basilar membrane results in relative motion between the tectorial membrane and the reticular lamina, causing deflection of the stereocilia and modulation of the open probability of their transduction channels. The resulting current causes a change of membrane potential, which in turn produces mechanical force, that is fed back into the motion of the basilar membrane. Experiments were conducted to address mechanical transduction mechanisms in both the stereocilia and the basolateral cell membrane, as well as modes of coupling of the outer hair cell force to the organ of Corti.

Epidemiological and experimental studies suggest that hypercholesterolemia promotes the development of sensorineural hearing loss; however, the underlying cellular pathomechanism remains obscure. In the present study, 20 healthy subjects and 20 patients with familial hypercholesterolemia were compared with respect to their hearing function. None of the 40 persons reported any history of hearing disorder. In accordance with this subjective impression, mean hearing thresholds were within the normal, age-dependent ranges in both groups. In contrast, the single-generator distortion product otoacoustic emissions (sgDPOAE) were reduced at and above 4 kHz. Input-output functions of DPOAE could be subdivided into three groups: (i) normal, with unity slope at low intensities and slope less than unity (0.24+/-0.07 dB/dB at higher intensities; (ii) pathologic, described by a single straight line; (iii) ill-defined, with data usually indistinguishable from the background noise level. The ill-defined DPOAE behavior was only found in patients with hypercholesterolemia; namely, for 25% of patients at f(2)=1.5 kHz and for 50% at f(2)=4 kHz. Patients belonging to the pathologic and ill-defined DPOAE groups had significantly (P0.05) higher total serum cholesterol and LDL-cholesterol levels compared with subjects from the normal DPOAE group. While hearing thresholds of patients with ill-defined growth functions were not statistically different from those of normal subjects, speech scores were significantly reduced in these cases. The data imply that nonlinear mechanical processes in the cochlea are compromised in hypercholesterolemic patients.

This study provides a detailed quantitative description of the acoustically evoked vibration responses in the low-frequency region of the in vitro guinea-pig cochlea. Responses of the basilar membrane, the reticular lamina and Hensen cells were measured with a laser Doppler vibrometer, without the need for introducing artificial light reflectors. The apex of the cochlea was opened, leaving the helicotrema intact. Two response components were detected: a ‘fast’ component, which was probably caused by the hole in the cochlea, and a ‘slow’ component, which shared the features of a classical travelling wave. The velocity response of the ‘slow’ component exhibited a relatively flat low-frequency slope (15 dB/oct) and a much steeper high-frequency roll-off (third turn: −47 dB/oct; fourth turn: −35 dB/oct). The group delay was dependent on the characteristic frequency. In the fourth turn, the sharpness of the velocity tuning curves ( Q 10 dB : 1.0) was similar to those of in vivo mechanical and neural recordings, whereas in the third turn the tuning ( Q 10 dB : 1.1) was much less than for in vivo recordings. The results indicate that cochlear amplification, which is responsible for the high sensitivity and sharp tuning in the basal part of the cochlea, is much less pronounced in the apical turn of the cochlea.

The transverse vibration response of the organ of Corti near the apical end of the guinea-pig cochlea was measured in vivo. For cochleae in good physiological condition, as ascertained with threshold compound action potentials and the endocochlear potential, increasing amounts of attenuation and phase lag were found as the intensity was decreased below 80 dB SPL. These nonlinear phenomena disappeared post mortem. The data suggest that an active, nonlinear damping mechanism exists at low intensities at the apex of the cochlea. The phase nonlinearity, evident at all frequencies except at the best frequency (BF), was limited to a total phase change of 0.25 cycles, implying negative feedback of electromechanical force from the outer hair cells into a compliant organ of Corti. The amplitude nonlinearity was largest above BF, possibly due to interaction with a second vibration mode. The high-frequency flank of the amplitude response curve was shifted to lower frequencies by as much as 0.6 octave (oct) for a 50-dB reduction of sound intensity; the reduction of BF was 0.3 oct, but there was no change of relative bandwidth (Q(10 dB)). Detailed frequency responses measured at 60 dB SPL were consistent with non-dispersive, travelling-wave motion: travel time to the place of BF (400 Hz at 60 dB SPL) was 2.9 ms, Q(10 dB) was 1.0; standing-wave motion occurred above 600 Hz. Based on comparison with neural and mechanical data from the base of the cochlea, amplitudes at the apex appear to be sufficient to yield behavioural thresholds. It is concluded that active negative feedback may be a hallmark of the entire cochlea at low stimulus frequencies and that, in contrast to the base, the apex does not require active amplification.

The tectorial membrane has long been postulated as playing a role in the exquisite sensitivity of the cochlea. In particular, it has been proposed that the tectorial membrane provides a second resonant system, in addition to that of the basilar membrane, which contributes to the amplification of the motion of the cochlear partition. Until now, technical difficulties had prevented vibration measurements of the tectorial membrane and, therefore, precluded direct evidence of a mechanical resonance. In the study reported here, the vibration of the tectorial membrane was measured in two orthogonal directions by using a novel method of combining laser interferometry with a photodiode technique. It is shown experimentally that the motion of the tectorial membrane is resonant at a frequency of 0.5 octave (oct) below the resonant frequency of the basilar membrane and polarized parallel to the reticular lamina. It is concluded that the resonant motion of the tectorial membrane is due to a parallel resonance between the mass of the tectorial membrane and the compliance of the stereocilia of the outer hair cells. Moreover, in combination with the contractile force of outer hair cells, it is proposed that inertial motion of the tectorial membrane provides the necessary conditions to allow positive feedback of mechanical energy into the cochlear partition, thereby amplifying and tuning the cochlear response.

The sound-induced travelling wave in the mammalian cochlea is believed to be enhanced and sharpened by a positive-feedback mechanism, causing the passive, linear growth function of the basilar membrane (BM) to become nonlinear. Based on direct measurements of the receptor potential of isolated outer hair cells, it is shown here how nonlinear BM motion might be due predominantly to the nonlinear growth function of the receptor potential. Since intensity coding in the inner ear is supposed to depend on an interaction of nonlinear BM motion with afferent fibres of different synaptic thresholds, intensity coding is expected to be directly dependent on the mechanoelectrical transduction of outer hair cells (OHC). According to the present experimental data and the feedback concept of outer hair cell action, disruption of the mechanoelectrical transduction of OHC leads to both a reduction of gain and linearizing of the response; that is, to both hearing loss and loudness recruitment.

Recent advances in optical techniques for vibration measurement have made it feasible to purchase commercially available laser Doppler velocimeters that, in combination with a light microscope, are capable of detecting velocities of poorly reflecting biological materials down to fractions of a micrometers s-1. Thus, in our particular application, the aim is to understand the micromechanics of the inner ear, particularly in the nanometer region where the ear is first able to detect sound. With currently available devices, it is now possible to make the necessary vibration measurements without need of introducing reflecting materials onto the object of interest. This not only avoids inertial loading, but also allows focusing through cellular layers onto otherwise inaccessible structures. Here we present the results of micromechanical experiments for the in vitro inner ear of the guinea pig, the most commonly used model in auditory physiology. Our experiments concentrate on the third and fourth cochlear turns because in this region the different cellular structures of the organ of Corti are optically accessible with present technology. The mechanical responses of all examined structures, including the basilar membrane, were equally frequency selective, but linear below 90 dB SPL, suggesting that active mechanical tuning is not as pronounced in the apex as in the base of the cochlea. This has important consequences for signal processing in the inner ear.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Hypothesis In situ evaluation of the vibration performance of a hybrid system for intracochlear fluid stimulation, constructed from a floating mass transducer (FMT) coupled to an electric acoustic stimulation (EAS) cochlea implant (CI) electrode. Background EAS uses both CI technology to restore severe-to-profound hearing loss at high frequencies and acoustic amplification for mild-to-moderate hearing loss in the low-to-mid frequency range. More patients with residual hearing are becoming candidates for EAS surgery because of the improved techniques for hearing preservation. Most patients with partial deafness fulfill the audiological criteria at low and mid-frequencies for the active middle-ear implant with FMT (VSB). The FMT of the VSB is a potential device for acoustical stimulation in EAS. Methods In seven fresh human temporal bones, stapes amplitude responses for fixation of a FMT to the long incus process (standard coupling) was compared with those for FMT fixation to a 20-mm inserted standard cochlea electrode array (31.5 mm) via the round window (Vibro-EAS). Vibration of the stapes footplate was measured by laser Doppler vibrometry. Results For 0.316 Vrms drive voltage, stimulation of the intracochlear fluid using a FMT-driven CI electrode (Vibro-EAS) yielded stapes amplitude responses comparable to those for acoustic stimulation with 84 dB SPL. These amplitude responses are 30 to 42 dB lower at frequencies up to 4 kHz than those for VSB standard coupling. Conclusion Intracochlear combined electrical and mechanical stimulation may be a viable technique for electroacoustic stimulation. A reliable technique for attachment or integration of the FMT to the cochlea electrode array has yet to be developed.