Vibration responses of the organ of Corti and the tectorial membrane to electrical stimulation

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 (<15 nm). The experiments provide phase relations between the different structures, which, dependent on frequency range and longitudinal cochlear position, include in-phase transverse motions of the TM, counterphasic transverse motions between the inner hair cell and OHCs, as well as traveling-wave motion of Hensen's cells in the radial direction. Mechanics of sound processing in the cochlea are discussed based on these phase relationships.     

Interaural correlations in normal and traumatized cochleas: length and sensory cell loss

Sizable intraspecies variations have been found in both the length of the organ of Corti (OC) and the amount of damage resulting from exposure to a particular ototraumatic agent. These variations have made it difficult to address certain research questions such as the susceptibility of the previously injured ear to further damage. If intra-animal correlation is high, the variability problem could be circumvented by using the two ears from a given animal for different aspects of the same study. Therefore, correlation coefficients were calculated for OC length and for percentage of missing inner (IHCs) and outer hair cells (OHCs) in a large sample of chinchillas which included controls and animals which had been exposed to noise or treated with ionizing radiation. The correlation coefficients were +0.96 for OC length, +0.93 for IHC loss, and +0.97 for OHC loss.     

Differential electrical excitation of the auditory nerve

The multichannel cochlear prosthesis requires an electrode stimulus configuration which produces a stimulus field spatially localized to each electrode. In this paper, a three-dimensional discrete resistance model of the cochlea was developed which exhibits electrical response properties similar to those observed during electrical stimulation of the cochlea. The model results suggest that the spatial attenuation of current within the cochlea varies greatly in magnitude, depending on the stimulus configuration. In addition, the model suggests that the spatial attenuation of current in both the auditory nerve fiber endings in the organ of Corti and in the myelinated fibers within the cochlear ground paths is different from the voltage attenuation in the scalar fluids. Therefore the efficacy with which a particular stimulus configuration differentially excites local terminal auditory nerve fiber populations cannot be deduced from scalar voltage measurements which have previously been recorded in the literature. Consequently physiological experiments were performed in the cat to measure the current distributions in the terminal nerve fiber region for monopolar and bipolar stimulation of the scala tympani, and also for stimulation between the scala tympani and the scala vestibuli. The mean length constants measured in the basal turn for these stimuli were found to be 12, 3, and 7.5 mm, respectively.     

The accuracy of hair cell counts in determining distance and position along the organ of Corti

The relationship between the density of hair cells (cells/mm) and measured distance along the guinea pig organ of Corti was determined using light microscopy and the surface specimen technique. It was demonstrated that the density of inner hair cells (IHC; mean 92.0 +/- 2.4) and 1st row of outer hair cells (OHC1; mean 118.7 +/- 2.3) did not show significant variation along the organ of Corti except within 0.5-1.0 mm of the apex and base where there was considerable variation between animals in the density of cells. There was a close relationship between the accumulated number of either IHC or OHC1 and distance from the base along the organ of Corti. Distances estimated by hair cell counts were similar to those determined by direct measurement. It is concluded that hair cell counts can be used to reliably estimate distances along the organ of Corti where accurate direct measurement is not possible, such as in scanning electron microscopy.     

Effect of outer hair cell piezoelectricity on high-frequency receptor potentials

The low-pass voltage response of outer hair cells predicted by conventional equivalent circuit analysis would preclude the active force production at high frequencies. We have found that the band pass characteristics can be improved by introducing the piezoelectric properties of the cell wall. In contrast to the conventional analysis, the receptor potential does not tend to zero and at any frequency is greater than a limiting value. In addition, the phase shift between the transduction current and receptor potential tends to zero. The piezoelectric properties cause an additional, strain-dependent, displacement current in the cell wall. The wall strain is estimated on the basis of a model of the cell deformation in the organ of Corti. The limiting value of the receptor potential depends on the ratio of a parameter determined by the piezoelectric coefficients and the strain to the membrane capacitance. In short cells, we have found that for the low-frequency value of about 2-3 mV and the strain level of 0.1% the receptor potential can reach 0.4 mV throughout the whole frequency range. In long cells, we have found that the effect of the piezoelectric properties is much weaker. These results are consistent with major features of the cochlear amplifier.     

Repeated TTS exposures in monkeys: alterations in hearing, cochlear structure, and single-unit thresholds

The findings of a number of studies investigating the effects of excessive sound on hearing have indicated that the correspondence between behavioral, physiological, and histological measures of noise-induced hearing loss may be markedly dependent upon the sensitivity of the particular measure. Recent studies demonstrating significant changes in the responses of single auditory neurons following brief exposures to pure tones suggest that single-unit activity may be a sensitive indicator of physiological insult to the organ of Corti's sensory cells. In addition, the long-lasting nature of the changes in neural responsiveness suggests that each temporary threshold shift (TTS) episode may produce an increment of damage to the ear that eventually contributes to a measurable permanent threshold shift (PTS). A logical extension of this implication is the proposal that repeated episodes of TTS would first affect single-unit thresholds, and that such damage would eventually manifest itself as PTS. A test of this notion was performed by repeatedly exposing monkeys to short-lasting TTS sounds for many months. Behavioral thresholds were monitored using a reaction-time task before and after each inducement of TTS. Two subjects participated in exposure sessions for 18 months, while the remaining monkey was exposed to identical stimuli for 6 months. At the end of behavioral testing, the monkeys were prepared for chronic recording from single cells of the cochlear nucleus. Following the recording period, cochleas were prepared for examination as plastic-embedded whole mounts. Flat preparations of the cochlear duct were made and the position and extent of damage to the organ of Corti and myelinated nerve fibers were determined. No elevations in behavioral threshold were noted for the monkey receiving 6 months of sound-exposure experience, while for both subjects exposed for 18 months, a significant high-frequency hearing loss became apparent during the final months of exposure. For damaged ears, the thresholds of ipsilateral cochlear nucleus units were elevated for characteristic frequencies (CFs) corresponding to the frequency regions where behavioral thresholds were shifted. Thresholds for units with high-frequency CFs in the animal exposed for 6 months also demonstrated a loss in sensitivity. Histological examination of the cochleas of monkeys with permanent hearing losses revealed corresponding damage to the high-frequency region of the organ of Corti. The monkey exposed for 6 months, which demonstrated only elevated unit thresholds, also had high-frequency lesions.(ABSTRACT TRUNCATED AT 400 WORDS)     

A model cochlear partition involving longitudinal elasticity

This paper addresses the issue of longitudinal stiffness within the cochlea. A one-dimensional model of the cochlear partition is presented in which the resonant sections are coupled by longitudinal elastic elements. These elements functionally represent the aggregate mechanical effect of the connective tissue that spans the length of the organ of Corti. With the plate-like morphology of the cochlear partition in mind, the contribution of longitudinal elasticity to partition dynamics is appreciable, though weak and nonlinear. If the elasticity is considered Hookian then the nonlinearity takes a cubic form. Numerical solutions are presented that demonstrate the compressive nature of the partial differential nonlinear equations and their ability to produce realistic cubic distortion product otoacoustic emissions. Within the framework of this model, some speculations can be made regarding the dynamical function of the phalangeal processes, the sharpness of active cochlear mechanics, and the propogation of pathology along the partition.     

Distortion product otoacoustic emissions in hearing-impaired mutant mice

The acoustic intermodulation distortion product (2f1-f2) was recorded in the ear canal of two different types of normally hearing mice and in four different types of hearing-impaired mutant mice. In the normally hearing animals, primary tones at levels of 60- to 100-dB SPL evoked distortion product emissions (DP's) at 20-50 dB below the primary levels. In the hearing-impaired mutants the level was dependent on the particular type of auditory dysfunction associated with the mutation. In both the deafness and the viable dominant spotting mutants, where either the whole organ of Corti or the stria vascularis is affected by the mutation, no DP's could be detected. The quivering mutant has a central auditory dysfunction associated with the nuclei of the superior olivary complex and the lateral lemniscus, with apparently normal cochlear function. DP's at levels and thresholds similar to those in normally hearing animals were recorded in quivering mice. The Bronx Waltzer mutant has a full complement of outer hair cells but only about of 20%-25% inner hair cells. DP's of small amplitude were recorded but the thresholds were raised by about 30 dB. The data suggest that the 2f1-f2 emission can be used as a noninvasive monitor of cochlear function.     

Intracochlear pressure and derived quantities from a three-dimensional model

Intracochlear pressure is calculated from a physiologically based, three-dimensional gerbil cochlea model. Olson [J. Acoust. Soc. Am. 103, 3445-3463 (1998); 110, 349-367 (2001)] measured gerbil intracochlear pressure and provided approximations for the following derived quantities: (1) basilar membrane velocity, (2) pressure across the organ of Corti, and (3) partition impedance. The objective of this work is to compare the calculations and measurements for the pressure at points and the derived quantities. The model includes the three-dimensional viscous fluid and the pectinate zone of the elastic orthotropic basilar membrane with dimensional and material property variation along its length. The arrangement of outer hair cell forces within the organ of Corti cytoarchitecture is incorporated by adding the feed-forward approximation to the passive model as done previously. The intracochlear pressure consists of both the compressive fast wave and the slow traveling wave. A Wentzel-Kramers-Brillowin asymptotic and numerical method combined with Fourier series expansions is used to provide an efficient procedure that requires about 1 s to compute the response for a given frequency. Results show reasonably good agreement for the direct pressure and the derived quantities. This confirms the importance of the three-dimensional motion of the fluid for an accurate cochlear model.     

Transfection using hydroxyapatite nanoparticles in the inner ear via an intact round window membrane in chinchilla

Hydroxyapatite nanoparticles (nHAT) are known to have excellent biocompatibility, and have attracted increasing attention as new candidates of non-viral vectors for gene therapy. In our previous studies, nHAT carrying a therapeutic gene and a reporter gene were successfully transfected into the spiral ganglion neurons in the inner ear of guinea pigs in vivo as well as in the cultured cell lines, although the transfection efficiencies were never higher than 30%. In this study, the surface modification of nHAT with polyethylenimine (PEI) was made (PEI–nHAT, diameter = 73.09 ± 27.32 nm) and a recombinant plasmid carrying enhanced green fluorescent protein (EGFP) gene and neurotrophin-3 (NT-3) gene was constructed as pEGFPC2–NT3. The PEI modified nHAT and the recombinant plasmid was then connected to form the nHAT-based vector–gene complex (PEI–nHAT–pEGFPC2–NT3). This complex was then placed onto the intact round window membranes of the chinchillas for inner ear transfection. Auditory brainstem response (ABR) was tested to evaluate auditory function. Green fluorescence of EGFP was observed using confocal microscopy 48 h after administering vector–gene complexes. There was no significant threshold shift in tone burst-evoked ABR at any tested frequency. Abundant, condensed green fluorescence was found in dark cells on both sides of the crista and around the macula of the utricle. Scattered EGFP signals were also detected in vestibular hair cells, some Schwann cells in the cochlear spiral ganglion region, some outer pillar cells in the organ of Corti, and a few cells in the stria vascularis. The density of green fluorescence-marked cells was obviously higher in the vestibular dark cell area than in other areas of the inner ear, suggesting that vestibular dark cells may have the ability to actively engulf the nHAT-based vector–gene complexes. Considering the high transfection efficiency in the vestibular system, PEI–nHAT may be a potential vector for gene therapy of inner ear diseases, especially vestibular disorders, and deserves further study.     

Cochlear transducer operating point adaptation

The operating point (OP) of outer hair cell (OHC) mechanotransduction can be defined as any shift away from the center position on the transduction function. It is a dc offset that can be described by percentage of the maximum transduction current or as an equivalent dc pressure in the ear canal. The change of OP can be determined from the changes of the second and third harmonics of the cochlear microphonic (CM) following a calibration of its initial value. We found that the initial OP was dependent on sound level and cochlear sensitivity. From CM generated by a lower sound level at 74 dB SPL to avoid saturation and suppression of basal turn cochlear amplification, the OHC OP was at constant 57% of the maximum transduction current (an ear canal pressure of -0.1 Pa). To perturb the OP, a constant force was applied to the bony shell of the cochlea at the 18 kHz best frequency location using a blunt probe. The force applied over the scala tympani induced an OP change as if the organ of Corti moved toward the scala vestibuli (SV) direction. During an application of the constant force, the second harmonic of the CM partially recovered toward the initial level, which could be described by two time constants. Removing the force induced recovery of the second harmonic to its normal level described by a single time constant. The force applied over the SV caused an opposite result. These data indicate an active mechanism for OHC transduction OP.     

Frequency map of the spiral ganglion in the cat

A frequency map of the cat spiral ganglion has been determined on the basis of reconstructed cochleas in which individual spiral ganglion cells were labeled with horseradish peroxidase following determination of their characteristic frequency; the cochleas were the same as those used by Liberman and Oliver [J. Comp. Neurol. 223, 163-176 (1984)]. By matching this map to one previously described for the organ of Corti [M. C. Liberman, J. Acoust. Soc. Am. 72, 1441-1449 (1982)], an estimate of the afferent innervation density of the inner hair cells was derived. Counts of myelinated nerve fibers at the habenula perforata and inner hair cells were also performed and yielded similar results in all but the most basal 10%-15% of the cochlea. Between 0.1 and 20 kHz there is a gradual monotonic increase as a function of frequency in the number of spiral ganglion cells terminating on each inner hair cell, from about eight ganglion cells per inner hair cell to about 30 ganglion cells per inner hair cell. Above 20 kHz, it seems there is a decrease to about ten ganglion cells per inner hair cell. The greatest innervation density is at approximately the region of the basilar membrane with the greatest density of inner hair cells per millimeter.     

Finding the impedance of the organ of Corti

Measurements of the nonlinear response of the basilar membrane to a pure tone are shown to have a simple form for moderate membrane velocities: V(x,f;Vu)/Vu approximately [V(x,f)/Vu]v(x,f), f less than or equal to fc(x), where the response V is the velocity of the membrane at measurement position x, Vu is the umbo velocity, f is the frequency of the stimulus, and fc(x) is the local characteristic frequency. The frequency dependence of the functions v(x,f) and V(x,f) is determined from the data, and v(x,f) and ln V(x,f) are shown to be analytic functions in the lower half of the complex frequency plane, with Re [v(x,f)] a monotonically increasing function of f at fixed x. The linear limit of basilar membrane motion is characterized by a transfer function T(x,f) = (V/V1)v/(1-v), estimated by extrapolating V(x,f;Vu)/Vu to a small membrane velocity V1.T(x,f) and ln T(x,f) are shown to be analytic functions in the lower half of the complex frequency plane. The inverse of the amplitude of the transfer function, which has both a deep dip at f approximately fc(x) and a broad shoulder at lower frequencies, bears a striking resemblance to the neural threshold tuning curve. The functional form of T(x,f) is used to deduce the equation governing the motion of a section of the organ of Corti. Each section acts like a negatively damped harmonic oscillator stabilized at time t by a feedback force proportional to the velocity at the previous time t-tau. The time delay tau is proportional to the oscillator period [tau approximately 1.75/fc(x)]. Like a laser, the organ of Corti pumps energy into harmonic traveling waves. Unlike the laser, the direction of energy flow abruptly reverses as the traveling wave approaches the point of maximum membrane velocity [fc(x) approximately f]. All accumulated wave energy is then pumped back into a small section of the organ of Corti where transduction presumably occurs. Outer hair cells are conjectured to be active elements contributing to the negative damping and feedback of the cochlear amplifier.     

Prediction of the characteristics of two types of pressure waves in the cochlea: theoretical considerations

The aim of this study was to predict the characteristics of two types of cochlear pressure waves, so-called fast and slow waves. A two-dimensional finite-element model of the organ of Corti (OC), including fluid-structure interaction with the surrounding lymph fluid, was constructed. The geometry of the OC at the basal turn was determined from morphological measurements of others in the gerbil hemicochlea. As far as mechanical properties of the materials within the OC are concerned, previously determined mechanical properties of portions within the OC were adopted, and unknown mechanical features were determined from the published measurements of static stiffness. Time advance of the fluid-structure scheme was achieved by a staggered approach. Using the model, the magnitude and phase of the fast and slow waves were predicted so as to fit the numerically obtained pressure distribution in the scala tympani with what is known about intracochlear pressure measurement. When the predicted pressure waves were applied to the model, the numerical result of the velocity of the basilar membrane showed good agreement with the experimentally obtained velocity of the basilar membrane documented by others. Thus, the predicted pressure waves appeared to be reliable. Moreover, it was found that the fluid-structure interaction considerably influences the dynamic behavior of the OC at frequencies near the characteristic frequency.     

A symmetry suppresses the cochlear catastrophe

When the independent spatial variable is defined appropriately, the empirical finding that the phase of the cochlear input impedance is small [Lynch et al., J. Acoust. Soc. Am. 72, 108-130 (1982)] is shown to imply that the wavelength of the pressure wave in the cochlea changes slowly with position near the stapes. As a result, waves traveling in either direction through the basal turn undergo little reflection, and the transfer of energy between the middle and inner ears remains efficient at low frequencies. The slow variation of the wavelength implies that the series impedance Z and shunt admittance Y of the cochlear transmission line are approximately proportional at low frequencies and thus requires that the width of the basilar membrane and the cross-sectional areas of the cochlear scalae taper in opposite directions. Maintenance of the symmetry between Z and Y is both necessary and sufficient to ensure that the spatial derivative of the wavelength, and hence the phase of the cochlear input impedance, remains small. Although introduced in another context, the model of Zweig ["Finding the impedance of the organ of Corti," J. Acoust. Soc. Am. 89, 1229-1254 (1991)] manifests the symmetry between Z and Y. In other transmission-line models of cochlear mechanics, however, that symmetry is absent, and the spatial derivative of the wavelength diverges at low frequencies--the "cochlear catastrophe." Those models therefore contradict the impedance measurements and predict little transfer of energy between the middle and inner ears.     

The mechanical waveform of the basilar membrane. IV. Tone and noise stimuli

Analysis of mechanical cochlear responses to wide bands of random noise clarifies many effects of cochlear nonlinearity. The previous paper [de Boer and Nuttall, J. Acoust. Soc. Am. 107, 1497-1507 (2000)] illustrates how closely results of computations in a nonlinear cochlear model agree with responses from physiological experiments. In the present paper results for tone stimuli are reported. It was found that the measured frequency response for pure tones differs little from the frequency response associated with a noise signal. For strong stimuli, well into the nonlinear region, tones have to be presented at a specific level with respect to the noise for this to be true. In this report the nonlinear cochlear model originally developed for noise analysis was modified to accommodate pure tones. For this purpose the efficiency with which outer hair cells modify the basilar-membrane response was made into a function of cochlear location based on local excitation. For each experiment, the modified model is able to account for the experimental findings, within 1 or 2 dB. Therefore, the model explains why the type of filtering that tones undergo in the cochlea is essentially the same as that for noise signals (provided the tones are presented at the appropriate level).     

A cochlear model for acoustic emissions

Variability in cochlear emission properties among different species, particularly humans and small mammals, and within individuals in the same species, is modeled by a cochlear nonlinear transmission line. The difference between humans and animals is largely explained by a lower cochlear input impedance in human ears than in cats, gerbils, or chinchillas. Inconstancy in emission properties among individual human or animal subjects is related to structural variability among ears, which can be the result of a nonuniform connection between the outer hair cells cilia and the tectorial membrane. These structural differences are modeled by a nonuniform cochlear partition resistance along the cochlear length. The model predicts that an ear which has a uniform cochlear partition resistance and an adequate cochlear input impedance will emit acoustic distortion products (ADP), but not spontaneous acoustic emission (SAE), nor click-evoked emission (CE). Only a nonuniform cochlea emits SAE and CE in addition to enhanced ADPs. The model predictions agree quantitatively with cochlear emission data from humans and animals.     

The representation of steady-state vowel sounds in the temporal discharge patterns of the guinea pig cochlear nerve and primarylike cochlear nucleus neurons

We have recorded the responses of fibers in the cochlear nerve and cells in the cochlear nucleus of the anesthetized guinea pig to synthetic vowels [i], [a], and [u] at 60 and 80 dB SPL. Histograms synchronized to the pitch period of the vowel were constructed, and locking of the discharge to individual harmonics was estimated from these by Fourier transformation. In cochlear nerve fibers from the guinea pig, the responses were similar in all respects to those previously described for the cat. In particular, the average-localized-synchronized-rate functions (ALSR), computed from pooled data, had well-defined peaks corresponding to the formant frequencies of the three vowels at both sound levels. Analysis of the components dominating the discharge could also be used to determine the voice pitch and the frequency of the first formants. We have computed similar population measures over a sample of primarylike cochlear nucleus neurons. In these primarylike cochlear nucleus cell responses, the locking to the higher-frequency formants of the vowels is weaker than in the nerve. This results in a severe degradation of the peaks in the ALSR function at the second and third formant frequencies at least for [i] and [u]. This result is somewhat surprising in light of the reports that primarylike cochlear nucleus cells phaselock, as well as do cochlear nerve fibers.     

Intracochlear pressure measurements related to cochlear tuning

Pressure in turn one of the scala tympani (s.t.) was measured close to the basilar membrane (b.m.) and at additional positions as the pressure sensor approached and/or withdrew from the b.m. The s.t. pressure measured within about 100 microm of the b.m. varied rapidly in space at frequencies around the region's best frequency. Very close to the b.m. the s.t. pressure was tuned and scaled nonlinearly with sound level. The scala vestibuli (s.v.) pressure was measured at one position close to the stapes within seconds of the s.t. pressure and served primarily as a reference pressure. The driving pressure across the organ of Corti and the b.m. velocity were derived from the pressure data. Both were tuned and nonlinear. Therefore, their ratio, the specific acoustic impedance of the organ of Corti complex, was relatively untuned, and only subtly nonlinear. The impedance was inspected specifically for negative resistance (amplification) and resonance. Both were detected in some instances; taken as a whole, the current results constrain the possibilities for these qualities.     

A cochlear frequency-position function for several species--29 years later

Accurate cochlear frequency-position functions based on physiological data would facilitate the interpretation of physiological and psychoacoustic data within and across species. Such functions might aid in developing cochlear models, and cochlear coordinates could provide potentially useful spectral transforms of speech and other acoustic signals. In 1961, an almost-exponential function was developed (Greenwood, 1961b, 1974) by integrating an exponential function fitted to a subset of frequency resolution-integration estimates (critical bandwidths). The resulting frequency-position function was found to fit cochlear observations on human cadaver ears quite well and, with changes of constants, those on elephant, cow, guinea pig, rat, mouse, and chicken (Békésy, 1960), as well as in vivo (behavioral-anatomical) data on cats (Schucknecht, 1953). Since 1961, new mechanical and other physiological data have appeared on the human, cat, guinea pig, chinchilla, monkey, and gerbil. It is shown here that the newer extended data on human cadaver ears and from living animal preparations are quite well fit by the same basic function. The function essentially requires only empirical adjustment of a single parameter to set an upper frequency limit, while a "slope" parameter can be left constant if cochlear partition length is normalized to 1 or scaled if distance is specified in physical units. Constancy of slope and form in dead and living ears and across species increases the probability that the function fitting human cadaver data may apply as well to the living human ear. This prospect increases the function's value in plotting auditory data and in modeling concerned with speech and other bioacoustic signals, since it fits the available physiological data well and, consequently (if those data are correct), remains independent of, and an appropriate means to examine, psychoacoustic data and assumptions.