Recent Developments in Auditory Mechanics

The following sections are included:

• Preface

• Photolegend

• Participants in the conference on RECENT DEVELOPMENTS IN AUDITORY MECHANICS

• Contents

Three anatomical features stand out about the eardrum. First, the eardrum has a pronounced conical shape. Second, the eardrum has a well organized substructure of radial and circular fibers. Third, the superior portion of cat eardrum lies along the ear canal wall while the inferior portion ends the canal at a 50 degree angle. This observation that the superior potion of the eardrum lies along the canal led to the hypothesis that the eardrum acts like an elastic wall of the ear canal. This would have the effect of significantly slowing the acoustic wave speed. Recently Puria and Allen have proposed that the eardrum has a transmission-line like behavior. The available experimental data seems to support this claim. As of yet, no model directly based on the eardrum's structure and geometry has been able to reproduce this type of behavior. The model presented in this paper tests the hypothesis that the eardrum's elasticity coupled with the inclination of the eardrum in the ear canal can explain this behavior. The results show that the eardrum's inclination and elasticity significantly contribute to the impedance response. The model agrees with the experimental data for frequencies up to 9 kHz.

A method is described that allowed for the first time intraoperative scanning laser Doppler interferometry (LDI) in human subjects. As an example how the middle ear can be assessed the study focused on the acoustic function of the posterior incudal ligament. The study was designed to answer the following questions: 1) Is our LDI system practical for taking measurements during surgery? 2) Are the results equal to the findings in temporal bone models? 3) Do the vibration characteristics of the middle ear change after the posterior incudal ligament is detached? Seven patients with profound bilateral hearing loss undergoing cochlear implantation were included in the study. Our measurement system was easily applicable for intraoperative measurements. No major difference of the results from live human subjects and temporal bone models occurred. Sacrificing the posterior incudal ligament had no significant effect on the postoperative hearing result.

The cat middle-ear air cavity is divided into two air spaces by an incomplete bony septum, such that the two spaces are connected by a narrow foramen. Measurements of middle-ear input admittance and cochlear potentials from cats with intact and modified middle-ear air spaces are used to test two hypotheses concerning the function of middle-ear septa. The data are consistent with the notion that septa act to smooth the middle-ear response at high frequencies by effectively reducing the size of the air spaces at frequencies where the impedance of the foramen is large, but do not support the idea that the septum acts to increase the sensitivity of the ear to high-frequency sounds. The former role may be relevant to the use of high-frequency spectral structure in determining the elevation of sound sources.

Volume displacement of the eardrum, and especially of the pars flaccida (PF), is traditionally seen as an important factor in middle ear pressure regulation. In this paper we present an in-vitro study of PF volume displacement as a function of pressure. The deformation was measured in five gerbil ears using an optical shape measuring technique, and volume displacement was determined at small pressure intervals in three sequential pressure cycles, in the range of ±0.4 kPa, ±2 kPa, and again ±0.4 kPa. Volume displacement did not increase for pressures beyond 800 Pa, and the major part of the maximal volume displacement was reached in a very small pressure range of a few hundred Pa. For all ears we found that maximal PF volume displacement was smaller than 0.2% of the ME volume. We also calculated middle ear pressure as a function of pressure in the external ear canal, taking PF volume displacement into account. These calculations were also performed using pars tensa (PT) displacement data obtained in our previous work. Over the entire pressure range, the contribution of the PT in middle ear pressure regulation is much larger than the contribution of the PF, and even the deformation of the entire eardrum only has a limited effect on ME pressure regulation. The contribution of the PF is marginal, and limited to a range of a few cm of water pressure.

The mechanisms of hearing loss in otitis media with effusion (OME), a common clinical condition, were investigated by measuring umbo motion with a laser vibrometer while different fluids were introduced into the middle ear of a human temporal bone preparation. Various amounts of saline (to simulate serous effusions) and glycerin (to simulate more viscous mucoid effusions) contacted part or all of the tympanic membrane (TM) and filled part or all of the middle ear. Reductions in umbo motion matched hearing losses reported with OME within 5 dB. Above 700 Hz, reductions depended mostly on the percentage of the TM contacted by fluid; below 700 Hz reductions depended mostly on the reduction in middle-ear air volume by the fluid. Results also suggested that the effects of glycerin viscosity are small (5–10 dB) and important only above 2 kHz.

Acoustical energy is transmitted from the tympanic membrane to the inner ear by the middle ear ossicles. It is generally accepted that the ossicles rotate around a fixed axis and function as mechanical levers. Measurements of malleus vibration made through the intact ear canal have clearly shown that the malleus motion is not a rotation about a fixed suspension axis but that translation and rotation components in all three dimensions are present and change dramatically over the frequency of hearing. An important question is how this malleus motion at the middle ear input is converted into motion of the stapes at the output where it defines the inner ear input. The motion of the stapes has been difficult to measure in the past because access is limited and only a small portion of the crura can be seen. In order to get a better access to the stapes a novel preparation of the cat temporal bone was utilized. To determine its 3-D motion, the vibration of the stapes was measured with a confocal heterodyne interferometer at three points from different viewing angles. Its geometry was also measured. Assuming that the system behaves as a rigid body, the stapes motion was calculated. Stapes morion calculated by finite-element modeling was also found to be three dimensional, in qualitative agreement with the experimental motion. The question arises of what functional role these 3-D vibrations play in hearing.

The achievement of structure-based volume geometry data of human temporal bones performs a necessary assumption for several applications in modeling and general visualization of the human hearing organ and its components. In consequence of evaluating various physical techniques for high-resolution temporal bone imaging mainly the results of non-invasive X-ray absorption microtomography will be presented here. By that approach many internal structures and components of temporal bone specimens have been imaged with spatial resolution in the 10 micron range and visualized three-dimensionally. The results indicate the high capabilities of that approach and promise further resolution enhancements into the submicron region. Furthermore they have been transferred into individual geometry models for simulation acousto-mechanic sound transfer through middle and inner ear.

Diseased hearing sometimes is repaired by insertion of passive or active implants into the middle ear. Multibody System models (MBS) are used to describe the three-dimensional motion of the normal and the reconstructed middle ear structure and the sound transfer through the middle ear. For the description of the ear drum the Finite Element approach is used. The parameters of the models are derived from different measurements on cadaver specimen and living subjects. Pathological situations are simulated by changing particular parameters and/or the structure of the model. The transfer characteristic of a reconstructed ear depends strongly on the design of the implant itself but also on the technique and the conditions of its insertion as well as on the remaining middle ear structure. The motions of the stapes and the umbo are discussed for a natural middle ear and compared with a pathological situation of a beginning otosclerosis. An active implant is applied to the manubrium or the long process of incus, different directions of excitation are considered. Undesired feed back due to sound radiation from the ear drum may lead to resonance effects.

A one-dimensional model that considers the standing-wave effect was applied to simulation of sound transmission in the external ear. The sound pressure at any location in the auditory canal could be predicted by summating the ingoing acoustic waves and outgoing waves. The calculated values of the sound pressure gain from the free field to the eardrum were similar to the experimental results. The increase of the high-frequency response achieved by using an earmold with a large-diameter bore could be almost completely explained by computer simulation with this model. The impedance of the human eardrum could be estimated by measuring the standing wave patterns. This model is applicable for predicting how the shape of sound transmission tubes can influence the frequency response of a hearing aid.

For many years considerable work has been done on modelling inner ear mechanics with the aim of checking hypotheses on the function of the active amplifier. A preponderant issue has been the replication of the experimentally measured amplitude and phase characteristics of the sharp tuning of basilar membrane motion at low intensities, putting increasing weight on realistic modelling of the micromechanics of the organ of Corti. From the point of view of a one-dimensional approach, it has become evident that more than one solution for the longitudinal distribution of the passive and active point impedance of the basilar membrane exists. Additional criteria for checking underlying hypotheses are the replication of suppression and distortion patterns, feedback stability and the amount of energy, which must be provided by the cochlear feedback system. The aim of the present work is to use the input impedance of the cochlea to investigate experimentally cochlear models in the active and passive intensity ranges. Our computations in the frequency domain follow a formalism first described by Kanis and de Boer [1]. A certain class of nonlinear, locally active models can be treated with this formalism [2]. Depending on the underlying model, we have found a difference in the magnitude of the input impedance between the linear passive and the linear active region of up to 14%, whilst in the compressive region each model showed a characteristic variation. In order to compare the behaviour of the cochlear models with reality, we have measured the input impedance at the tympanic membrane of healthy human subjects using heterodyne laser interferometry. We were able to record the impedance down to sound pressure levels of 50 dB SPL at a stimulus frequency of 3 kHz. Between 50 and 70 dB SPL, which is theoretically within the compression region, we have found an input impedance variation of 20% compared to higher sound pressure levels in the linear passive region. In summary, we have evidence that the intensity dependence of the input impedance of the cochlea can be measured at the tympanic membrane.

In this study, a three-dimensional FEM model of a human middle ear was established, and the antorograde and retrograde pressure gains of the normal and pathologic middle ears were analyzed. Then, the levels of otoacoustic emissions (OAEs) in pathologic cars such as secretory otitis media, otosclerosis and incudo-stapedial joint separation were estimated based on the obtained pressure gains. The OAE frequency characteristics showed distinctive patterns depending on the kind of disorder and its degree.

The effects of lidocaine on basilar membrane (BM) vibration and compound action potential (CAP) were studied in young guinea pigs in order to elucidate the acting site of lidocaine in the cochlea. The BM vibration was measured with a laser doppler vibrometer through an opening made on the bony wall of the scaia tympani at the basal turn. Ten minutes after local administration of lidocaine into the scala tympani, the velocity of BM vibration and CAP amplitude decreased significantly at around the characteristic frequency (CF) of the stimulus sound (p<0.05). The maximum decrease was 4 dB in the velocity of BM vibration and 40 dB in the CAP amplitude. In contrast, such change was not observed after intravenous injection of lidocaine. The present results suggest that lidocaine acts not only on the outer hair cells but also on the cochlear nerve when it is administered into the scala tympani.

Inwardly rectifying K⁺ (Kir) channels play pivotal roles in regulation of excitability of the cells and setting their resting membrane potential in various tissues. However, the expression and function of Kir channels in inner ear have not been fully elucidated. Here we report that a Kir channel, Kir4.1/K_AB-2, is crucial for auditory function in cochlea of inner ear. Using the electrophysiological experiment, RT-PCR method, and immunohistochemistry, we found that Kir4.1 was specifically expressed at the basolateral membrane of marginal cells in stria vascularis and might play the central role in formation of positive endocochlear potential [3]. Furthermore, in satellite cells of cochlear ganglions, we detected the specific localization of Kir4.1 on their myelin sheaths with immunogold electron microscopy, suggesting that Kir4.1 is responsible for regulation of K⁺ ions extruded from the ganglion neurons during excitation [4]. Therefore, Kir 4.1 may be indispensable for proper function of inner ear.

To date, mechanical measurements in chinchilla cochleae are available only for two regions, one at a basal site and the other at the apex (3.5 and 14 mm from the oval window, respectively) We have begun to study basilar-membrane vibrations at the hook region of the chinchilla cochlea, at sites with CF ∼15 kHz located ∼1.7 mm from the stapes. At this time, results are available only from cochleae substantially traumatized by surgical procedures. Nevertheless, these results reveal basilar-membrane response properties qualitatively similar to those of the 3.5-mm site in healthy preparations. At frequencies well below CF, responses to tones are linear. Around CF, responses exhibit nonlinear behavior: vibration magnitudes grow with stimulus intensity at compressive rates and phases display lags and leads, respectively, at frequencies lower and higher than CF. Phase-vs.-frequency curves consist of a low-frequency segment with shallow slope, a steep-slope segment at frequencies near CF, and a plateau at higher frequencies.

Travel times for forward traveling waves were estimated by computing the group delay for the cochlear microphonic (CM) measured with an electrode in scala media and reverse travel times were estimated using electrically-evoked otoacoustic emissions (EEOE) generated using the same electrode. The results from these experiments were compared to each other as well as to round-trip travel times estimated using cubic distortion-product otoacoustic emissions (DPOAE). Our results suggest that, for the middle and basal regions of the cochlea, forward and reverse traveling waves have similar velocity-place profiles. In the cochlear apex, it appears that the traveling-wave mechanics may be more complex.

Experimental observations of sound-evoked vibrations of the cochlear partition are presented. The vibrations are shown to vary widely in amplitude, but little in phase, across the width of the partition. The radial amplitude profile is shown to be asymmetric and stable across a wide range of conditions. The largest vibrations are observed between the midline of the basilar membrane and the feet of the outer pillar cells. Differences between the phase of the vibrations in the arcuate and pectinate zones of the partition are observed under certain conditions, but these rarely exceed 30 degrees in magnitude.

Inner hair cell (IHC) pseudotransducer functions, obtained from cells with best frequencies at ∼1,000 Hz and ∼17,000 Hz [3, 26] reveal differences in asymmetry. The greater asymmetry expressed at the base of the cochlea results in generation of even-order distortion products at near threshold levels. The influence of these harmonic components on response phase may be important in the high frequency region of the cochlea. This is because transmitter release at very low frequencies depends on the difference between nonlinear intracellular and more linear extracellular potentials, i.e., the basolateral membrane potential gradient [25, 4].

A study of the longitudinal coupling within the organ of Corti (OC) was performed in the excised gerbil cochlea. Our data indicate that the coupling in the OC increases from base to apex. The cells of the OC increase the overall coupling exhibited by the basilar membrane (BM). The coupling in the reticular lamina is greater than in the BM. These results were used to estimate parameters for a one-dimensional model with longitudinal coupling. The peak of the predicted traveling wave was then broadened and delayed.

Sealed apical turn of the cochlea in living guinea pigs was viewed with a confocal microscope through the intact Reissner's membrane. Cellular vibration, in response to sound, was measured with a confocal laser heterodyne interferometer. Velocity tuning curves of the outer Hensen's cell and adjacent basilar membrane were measured, before and after sacrificing the animal. Initially the Hensen's cell velocity was 500 times higher than that of the basilar membrane (BM), demonstrating amplification. After sacrifice, BM velocity increased by a factor of 40 and tuning became sharper. This was followed by a decrease in the Hensen's cell velocity by a factor of about 10 and a decrease in tuning. After 250 minutes the ratio of Hensen's cell to BM velocity was reduced to 4. This sequence and the magnitude of changes show that the apical turn has amplification with negative feedback, and after sacrifice the amplification decreases with time.

In this paper we would like to make three key points. First, neural two tone suppression (2TS), by low frequency suppressors on high frequency probes, and the upward spread of masking (USM) are alternate measures of the same nonlinear cochlear mechanism. The two have similar (i.e., essentially equal) thresholds and growth rates. Second, the thresholds of neural 2TS, and of the USM, as a function of the probe frequency, are nearly independent of frequency, and are close to 65 dB SPL. Third, we discuss and model the level dependence of 2TS and the USM, which experimentally has previously been found to be about 2.4 dB/dB in both cat and human…

The ratio of the pressure across the organ of Corti to the velocity of the basilar membrane (b.m.) is the impedance of the organ of Corti (o.c), representing it's fundamental macromechanical properties. The purpose of this study was to examine the impedance for resonance and negative resistance. The presence of a resonance in the o.c. impedance is widely accepted as the basis for many characteristics of b.m. motion. [3] Our results support its existence. In contrast, the existence of negative resistance is the subject of active debate. Here we present data from two experiments which showed strong nonlinearity. In a strict sense, both of these experiments provide evidence for negative resistance: over a restricted range of frequencies below the characteristic frequency the phase of the b.m. velocity led the phase of the pressure across the organ of Corti by more than 90°. A broader view of the data indicates that in a nonlinear cochlea, the distortion of the moving o.c. might depend on stimulus level.

Electrically induced length changes of outer hair cells (OHC) of the mammalian cochlea are thought to be the main energy source for cochlear amplification. While vibration measurements on isolated outer hair cells of the guinea pig have shown that OHCs can produce constant force and displacement over the entire hearing range, it is not clear if OHCs in vivo, embedded in the Organ of Corti (OC), can still produce enough force to enhance mechanical tuning up to high frequencies. Therefore, we further investigated the role of cochlear OHCs in vivo by measuring the mechanical impedance, the electromechanical force and the displacement of the OC using an in vitro preparation. Our data clearly show that OHCs in situ are able to generate mechanical forces over the entire hearing range with almost constant displacement amplitudes up to 20 kHz. Amplitude values seem to be sufficiently large to account for the role of the OHCs as electromechanical elements in a cochlear amplifier. The displacement data with and without tectorial membrane support the view that underlying the exquisite sensitivity and frequency selectivity of the cochlea, is a complex radial vibration pattern of the OC with different vibration modes.

We had found in the past that deplarization of the OHCs and related depolarization of Hensen's cells did not necessarily occur during basilar membrane displacement toward scala vestibuli, as prescribed by the classical model of hair cell stimulation, but changed the response phase with sound frequency and intensity by as much as 180o. It is shown here with the help of network model analysis that the changes can be accounted for in detail almost entirely by variation of the mechanical resistance values of the tectorial membrane and the stereocilia, which may be produced by the active feedback. Above 80 dB SPL, the effective stiffness of the stereocilia also appears to change.

Previously, the only model that supported multiple propagation modes and had been shown to mimic cochlear mechanical data was the TWAmp [6,7,8]. We have formulated a three-compartment model that also allows multiple propagation modes. The model represents fluid flow in the organ of Corti, active and passive outer hair cell force production, the reticular lamina and basilar membrane, and the cochlear scalae. We found that this model also produces cochlea-like responses using realistic parameters and parameter settings.

Two simplifying assumptions were made in a frequency-domain formulation of two 1 − D transmission-line cochlear models: (1) the parallel impedance is a series LRC circuit whose resonant frequency varies exponentially with the distance x from the stapes; and (2) the characteristic impedance Z₀(s) with the complex angular frequency s is independent of x. When Z₀(s) is real (respectively, complex), we can get an integrable passive (respectively, active) model. In this paper, we first review a class of transmission-line models with the constant characteristic impedance. Secondly, we give a cascaded transmission-line model consisting of two active sections and one passive one and make it clear that such a model gives a solution to the the cochlear compromise problem and sharp maximum vs. wave reflection paradox and provides a computational model for simulating Kemp echo.

A nonlinear time-domain version of a previously published “feed-forward” model of the cat cochlea [4] was developed. The only nonlinear elements in the new version are saturating outer-hair-cell motile forces. Model responses to pure tones showed strongly compressed responses for characteristic-frequency (CF) tones. When a CF tone was presented along with a “low-side” suppressor tone, the responses produced by the CF tone were reduced, both tonically and, within a 2-kHz frequency limit, phasically. Suppression of CF-tone responses was also produced with “high-side” suppressors. Where available, two-tone suppression data measured experimentally on the basilar membrane in the basal region are very similar to the corresponding output of the model, thereby providing good support for the latter.

This study presents an implementation of our basic ideas about a time-domain nonlinear model of the cochlea. The time-domain approach is considered necessary because it allows implementation of nonlinearity in general and of a proper temporal analysis of natural transient responses in particular. It should be considered a useful step towards a realistic biophysical model of the cochlea, which so far has been claimed by several colleagues, but in my opinion is still far from being accomplished. Several very different approaches are worked out separately, but convergence to a general solution remains to be achieved, as is also clear from a number of presentations at this conference. In this paper I will briefly mention some of the problems of current state of the art approaches. Unfortunately I will not be able to give all the solutions. I will focus on the general structure of a useful as well as promising model.

Recently we developed a helicoidal box model of the cochlea [1] to address the hypothesis that coiling may have a functional significance. In that study we introduced nonorthogonal helicoidal coordinates, and introduced the WKB expansion to treat wave propagation in a slowly-varying geometry, and then numerically computed the fluid motion in a plane containing the modiolar axis using finite differences. We showed that coiling reduces the inertial impedance to fluid motion induced by the traveling wave. Since the effect was greatest at the apex, we suggested that the characteristic snaillike shape of the mammalian cochlea could increase the low frequency response of the cochlear partition. Here we study a simplified model where radial derivatives are neglected, which is a helicoidal version of what de Boer refers to as a “two dimensional classical model” of cochlear mechanics [2]. The eikonal equation, which determines the local wavenumber, and the transport equation, which determines the amplitude of the wave, can be analytically obtained for our simplified system. We find that spiraling inward from base to apex geometrically amplifies the wave in proportion to the inverse of the square root of the distance from the modiolar axis to the basilar membrane center line.

A detailed electromechanical model of the OHC was developed to simulate a wide variety of physiological experiments. All model parameters were biophysically based. The feedback model simulations were found to replicate the experimental data closely. Therefore this model is a useful quantitative tool for the interpretation of the effects of various experimental manipulations.

Simple models of the cochlea that represent the partition using a few degrees of freedom at each cross-section are able to simulate the measured gain of the real cochlear amplifier. However, validation of the assumptions inherent in the formulation of these models is hindered by difficulties associated with obtaining experimental data in vivo. This paper presents data from a more complex model that contains a cochlear partition with more than one hundred degrees of freedom at each cross-section. The model includes the organ of Corti as a three-dimensional structure sitting on top of the basilar membrane, and embeds the organ within the cochlear fluids. In the model, the effect of outer hair cell motility on the basilar membrane response is non-monotonic, explaining the apparently paradoxical effects of acetylcholine observed experimentally. Furthermore, the model exhibits fundamentally different behaviour under different stimulus conditions. Models that possess sophisticated representations of the cochlear partition may aid research into the operation of the cochlear amplifier.

The debate about whether we hear through a mechanism involving a bank of bandpass filters or through a traveling-wave mechanism was settled by Bekesy in favor of traveling waves. Experience gained in the engineering design and analysis of a silicon cochlea suggests why we may have evolved a traveling-wave mechanism for hearing: Distributed traveling-wave amplification is a vastly more efficient way of constructing a wide-dynamic-range frequency analyzer than is a bank of bandpass filters. Traveling-wave mechanisms are however, more susceptible to parameter variations and noise. Collective gain control and an exponentially tapering set of filters can solve both of these problems; the biological cochlea implements both of these solutions. These engineering studies suggest that the biological cochlea, which is capable of sensing sounds over 12 orders of magnitude in intensity while dissipating only a few microwatts, is an extremely well-designed sensing instrument. We illustrate the engineering principles in the cochlea by demonstrating a 117-stage adaptive silicon cochlea that operates over six orders of magnitude in intensity over a 100Hz–10kHz frequency range while only consuming 0.5mW of power. This artificial cochlea with automatic gain control and a low-noise traveling-wave amplifier architecture has the widest dynamic range of any artificial cochlea built to date.

A preliminary life-sized physical model of the cochlea is built. The model consists of a tapered polyimide basilar membrane bonded on a silicon wafer substrate and enclosed in two fluid-filled chambers. Measurements of the membrane responses compare roughly with mathematical simulations. The mathematical model used in the simulation takes into account the three-dimensional viscous fluid effects, the exact geometry and material properties in the physical model. Phase accumulation in the responses indicates the presence of a traveling wave. Due to the isotropy of the membrane, a broad tuning in the amplitude is obtained. The response can be sharpened by etching ribs into the membrane making it orthotropic, like the real biological membrane. The model can be extended to a more realistic model in the future, by adding details to the basilar membrane structure (like the spiral osseous, and the arcuate and pectinate zones) and active actuators emulating the outer hair cells.

Recently, the gammachirp function was proposed as an auditory filter for explaining psychoacoustical masking data [7]. It can also account for some basic physiological observations such as the frequency glide in basilar membrane motion (BMM), but it cannot readily account for other observations such as the nonlinear compressive relationship between signal level and BMM. In this paper, the gammachirp filter is extended to include an extra stage of filtering as suggested by the NonLinear Resonant Tectorial Membrane (NL-RTM) hypothesis [1,2]. The extra filter was initially proposed for an IIR implementation of the gammachirp [8]. The new gammachirp filter provides excellent fits to human masking data, and it enables us to unify physiological and psychoacoustical data within a common modelling framework.

A one-dimensional cochlear model is made active by incorporating feedback forces from outer hair cells (OHC). The mechanics of this model are nonlinear because the OHC force is limited by a saturating mechano-electric transduction stage. Distortion products in this model, measured in the acoustic pressure at the eardrum, demonstrate compressive growth at moderate levels and more rapid growth at the lower and higher levels. The compressive growth is primarily due to saturation of the OHC force. Loudness is estimated in this model from the simulated neural spike-discharge rate, which is integrated across all inner hair cells and across time. Log-loudness shows more rapid growth at low-levels and compressive growth at moderate levels, due to saturation of the OHC feedback force. Results from this cochlear model are compared with measurements of DPOAE and loudness growth in humans.

A model of cochlear micromechanics is proposed in which the tectorial membrane is driven by the fluid of the cochlea directly instead of the stereocilia of outer hair cells. It assumes that the tectorial membrane has almost the same acoustic resistance as the surrounding fluid, so that it can easily be driven by the fluid. Three-dimensional analysis of a macromechanical block model reveals a substantial radial flow that can drive the tectorial membrane. When it is combined with the block model, it has vibration of the tectorial membrane caused by the fluid and consequently it can produce satisfactory excitation curves of the basilar membrane while it simulates the phase of outer hair cell membrane potential.

The cochlear partition is considered as a system of two long elastic plates connected by a raw of springs — outer hair cells. The theory of multi-degree-of-freedom systems is applied to study the free and forced vibrations of a cross section of such a system. The model supposes that the fast oscillations of the outer hair cell are forced with the collective vibrations of the components of cochlear partition, while the slow motility appears to be an externally applied variation of mass and stiffness of the cell — the coupling agent between the basilar and tectorial membranes. The results of numerical computations submitted in the present paper support essentially the theoretical consideration of such a problem [2]. The simplified study of forced vibrations of a cross section demonstrates widening, lowering, and splitting of the tuning curve. The similar experimental findings and the alternative models have been widely discussed in literature.

Salicylate (SAL) is a member of an amphipath family that bends membranes outward while chlorpromazine (CPZ) belongs to an amphipath family that bends membranes inward. Two of the outer hair cell lateral wall's three layers are direct targets for amphipathic drugs because they are composed of membranes. Since SAL and CPZ are known to alter membrane-curvature, mechanics, and fluidity, we have measured the effect of these drugs on the passive mechanical properties of the outer hair cell lateral wall. The lateral wall was deformed using either micropipette aspiration or by applying a micropipette applied fluid jet and the resulting change in cell shape is measured. Both amphipaths result in an increase in the cell's diameter following the plasma membrane vesiculation that accompanies aspiration. CPZ significantly decreases the pressure required for vesiculation and the mean time for vesicle formation while SAL has no effect. Both agents decrease plasma membrane water permeability. It is perplexing that SAL reversibly blocks electromotility and causes a reversible hearing loss while CPZ has no obvious effect on either electromotility or hearing.

When a static deflection is superimposed on a sinusoidal displacement of the hair bundle, abolition of the phasic receptor current is observed. Simultaneously, the total current was maximized or minimized depending on the direction of stimulation. In response to negative, inhibitory displacements, some cells exhibited not only a reduction of the phasic receptor current but an additional reduction of current. This indicates the existence of mechanosensitive channels, being only sensitive to these extremely slow hair-bundle displacements. This so-called DC-shift appears to be very similar to the DC-shift that was described in response to application of dihydrostreptomycin (DHSM). In addition to this finding, many isolated OHCs did not react to sinusoidal mechanical stimulation, but showed modulated current flow when stereocilia were statically deflected. If both the pharmacological block by DHSM and the tonic mechanosensitivity are the responses of transducer channels, having lost their tip links during the isolation procedure, this indicates the presence of tip-link independent gating of hair-cell transduction channels.

The mechanism of voltage-dependent motility of the outer hair cell appears unique among biological motility in that it depends on electrical energy. Here we provide evidence that charge transfer measured as nonlinear capacitance and area changes of the outer hair cell membrane are tightly coupled. We digested the interior of the hair cell with trypsin and inflated the cell into a sphere with a patch pipette. If the cell is fully inflated, a membrane area constraint can be imposed on the cell by applying a short voltage waveform not to allow volume changes. This condition significantly reduced the nonlinear capacitance of the cell, indicating reduced charge transfer. By reducing pressure applied to the pipette, the nonlinear capacitance recovered. Increasing the duration of the waveform and thereby allowing changes in the cell volume also increased the nonlinear capacitance. Thus membrane area constraint and reduction in charge transfer are tightly linked. Since the cells we examined were internally digested, our results also show that the motile element likely resides in the plasma membrane.

Rapid changes in intracellular free Ca²⁺ concentration ([Ca²⁺]_i) were evoked by focal applications of extracellullar ATP to the hair bundle of outer hair cells (OHCs). Simultaneous recordings of the whole-cell current and Ca²⁺ signal showed a two-component increase in [Ca²⁺]_i. After an initial entry of Ca²⁺ through the apical membrane, a second and larger, InsP₃-gated, [Ca²⁺]_i, surge occurred at the base of the hair bundle. Electron microscopy of this intracellular Ca²⁺ release site showed that it coincides with the localization of the Hensen's body. We showed that InsP₃ receptors share this location. We also determined that an isoform of G proteins is present in the stereocilia. The ATP-evoked [Ca²⁺]_i rise did not interfere with the OHC electromotility mechanism. This second messenger signaling mechanism bypasses the Ca²⁺-clearance power of the stereocilia and transiently elevates [Ca²⁺]_i at the base of the hair bundle, where it can potentially modulate the action of unconventional myosin isozymes involved in maintaining the hair bundle integrity and thus influence mechano-transduction.

The outer hair cell (OHC) differs from other hair cells in that: it is a cylindrical, cellular-hydrostat; it exhibits electromotility (voltage-driven length changes); and it has an intracellular structure known as the subsurface cisterna (SSC). The cylindrical OHC is approximately 9μm in diameter and 20-80μm in length. The OHC has a concentric cylindrical geometry comprised of an inner compartment (the axial core) located inside the SSC and a narrow (30nm) annular compartment (the extracisternal space) between the SSC and the plasma membrane (PM). A previous study, using static ionic concentrations, predicts that the primary path of longitudinal current flow may be the narrow and highly resistive extracisternal space, indicating that the PM cannot be effectively space-clamped (Halter et al., 1997). In this paper we employ a new electrodiffusion model to explore the influence of ion concentration dynamics on the electrical properties of the OHC.

The mechanism of outer hair cell (OHC) electromotility is associated with the lateral wall. Understanding the interplay between the cytoskeleton and the plasma membrane is the key to understanding electromotile force generation and transmission. We sought to investigate the lipid-protein interactions associated with the motor complex by measuring the fluidity of the phospholipid bilayer as a function of membrane potential. Guinea pig OHCs were isolated and stained with a fluorescent membrane lipid (di-8-ANEPPS). The lateral diffusion of di-8-ANEPPS in the plasma membrane was measured using the technique of fluorescence recovery after photobleaching (FRAP). Voltage-clamping the OHCs in the whole-cell mode controlled the potential across the plasma membrane. Additionally, drugs known to alter membrane curvature in red blood cells (chlorpromazine and salicylate) were used to modify OHC membrane architecture. The fluidity of the plasma membrane has a voltage dependence resembling that of electromotility. Depolarizing the OHC decreased the lateral diffusion of intramembrane lipids by about 50%. Application of either chlorpromazine or salicylate alone also reduced the diffusion coefficient of the OHC plasma membrane by about 50%, while application of them together caused no significant change in the diffusion coefficient from controls. One potential explanation of the voltage- and drug-dependence of lateral diffusion in the OHC is that tension within the membrane in response to cell length changes or drug application creates bending of the plasma membrane. The bending is organized by the cytoskeleton into circumferential nanoscale ripples.

The composition of the cross links between stereocilia has been investigated to provide clues to their possible mechanical properties. The association of the links with keratan sulphate proteoglycans, their sensitivity to elastase (an enzyme that degrades a range of proteins), and their lack of immunoreactivity to elastin itself, suggests that they may contain a different extracellular matrix protein, such as a collagen-like molecule. We have therefore attempted determine whether the links contain collagen. Post-embedding immunogold labelling of the cochlea with an antibody to collagen IV produces labelling of the basilar membrane, as expected, but also of the hair bundle. Preadsorption with pure collagen IV reduces this labelling selectively. In addition, the enzyme MMP-2, which is more selective against collagen IV than against most other matrix proteins, degrades both tip and lateral links in utricular hair bundles. These data suggest that a collagen IV-like molecule may be a component of the links between stereocilia.

A computational model of the outer hair cell cytoskeleton as a domain-structure composite with narrow bands of an intermediate material between the domains is proposed. The random microstructural parameters of the domains are introduced. The effective moduli of the anisotropic cytoskeleton are computed and presented in the form of histograms. An unusual pattern of the cytoskeleton circumferential deformation caused by the high stiffness of the filaments within the domain compared to that for the connective molecule between the domains is discovered.

Two models of cochlear outer hair cell voltage-dependent length and stiffness are presented. While numerous models have been published to represent length changes, stiffness change is a newly discovered phenomenon. A parsimonious approach is to represent both voltage-dependent variables by a single mechanism. One of our models envisions a motor molecule undergoing conformational change and thereby representing two different lengths and stiffnesses. Stochastic summation of the effects of the individual molecules provides overall length and stiffness variation of the cell. The other model assumes no dimensional change, only stiffness change. In conjunction with pre-shortening of the cell, this model also provides overall length and stiffness change.

In this study, OHCs are stimulated by 5.0Hz and 105.3Hz sinusoidal voltage, and the local displacements along the cell axis are measured using microspheres attached on the cell lateral wall. When the cells are stimulated by 5.0Hz sinusoidal voltage, the displacement values are constant in the basal and apical regions, and the amount of the displacements varies almost linearly in the middle region of the cell. This suggests that there are no motors in the basal and apical regions of the cell and the motors are distributed equally in the middle region, if the effects of the mechanical properties of the cell lateral wall and the internal pressure are ignored. When the cells are stimulated by 105.3Hz sinusoidal voltage, the basal and apical regions of the cells elongate locally, and the phase differences among the measurement points are noticeable. This would be caused by the inertia and damping effects of the cell.

The distribution of long-chain carbocyanine dyes in the plasma membrane of living guinea pig outer hair cells (OHCs) was investigated by confocal microscopy, patch-clamp and image analysis techniques. Anionic carbocyanines labeled discrete patches on the lateral plasma membrane of OHCs, but not in supporting cells. Electrical stimulation through a patch-clamp pipette induced OHC motility and, simultaneously, lateral displacement of the fluorescent probes. Displacements were inhibited by microinjection of the cells with salicylate, a blocker of OHC motility. In turn, changes in the cortical cytoskeleton induced by cell microinjection either with trypsin or Toxin B from Clostridium difficile, did not inhibit the lateral displacement of the fluorescent probes, but changed its pattern. Together, these results suggest that the electrically-induced lateral displacement of fluorescent probes in the OHC plasma membrane is driven by the force-generator mechanism, and that it is very sensitive to the integrity of the cytoskeleton.

It has been shown that the membrane motor of the outer hair cell uses energy obtained by transfer of charge across the membrane. To study the kinetics of motor associated charge transfer across the membrane, we observed the power spectrum of current noise and the frequency dependence of the membrane capacitance from giant patches formed on the lateral membrane of the outer hair cell. The noise spectrum was inverse Lorentzian and the capacitance had Lorentzian frequency dependence as theoretically expected. The characteristic frequency for the capacitance was about 10 kHz and the one for current noise was somewhat higher. The magnitudes of noise, however, was larger than the theoretical prediction based on the capacitance data. This result appears to indicate that different mechanical constraints affected the two quantities monitored.

We propose a new mechanism for outer hair cell electromotility based on the physics of liquid crystals. In this “orientational motor model”, the plasma membrane of the outer hair cell contains a high density of molecular dipoles capable of orienting in an applied electric field. The molecular reorientation results in a membrane curvature change. This well-documented phenomenon is termed the “flexoelectric effect.” The fraction of dipoles oriented in the direction of the applied field is described by the Langevin function. We develop a formal nonlinear theory of outer hair cell electromotility from a thermodynamic potential function and show that the resulting constitutive equation is able to predict outer hair cell voltage-dependent motility. The nonlinear capacitance of the outer hair cell will also be described by a Langevin function and we discuss the evidence in support of this. The orientational motor model is consistent with both protein and lipid based molecular mechanisms of motility and provides an explanation for the effect of salicylate and diamide on electromotility. In addition, the model suggests that voltage-dependent lateral diffusion of fluorescent probes in the lateral wall plasma membrane is a reflection of the altered orientation of membrane dipoles.

The study of temporal aspects of otoacoustic emissions (OAEs) provides useful information concerning the sources of the emissions and helps to test and constrain cochlear emission models. A unified model, which successfully describes many of the characteristics of the various types of spontaneous and evoked otoaocoustic emissions and the related microstructure of the hearing threshold, has been recently formulated [1]. The model is based upon wave reflections via distributed spatial inhomogeneities and tall and broad cochlear activity patterns, as suggested by Zweig and Shera [2]. The model may be used to explore a number of issues relating to the temporal properties of OAEs. For example, in the case of the 2f₁ – f₂ distortion product OAE (DPOAE), in which one of the primaries is on continuously and the other is pulsed on and off, the data can be interpreted in terms of approximate analytic time-domain solutions, which clearly exhibit the various characteristic latencies [3] as well as the level dependencies of cochlear wave reflections. It is also shown that when the higher frequency (f₂) primary is pulsed on, the latency of the earliest DPOAE component is significantly different from the f₂-sweep group delay which is inferred from DPOAE phase data for steady state primaries [e.g., Bowman et al. [4]]. The model also allows an investigation of the so-called “filter build-up time” contribution [4] to the f₂-sweep group delay. It is shown that this contribution is small, and that the substantial difference between the f₂-sweep and f₁-sweep group delays, which has been attributed to the cochlear filter, may be largely accounted for by the implications of the approximate scale invariance of cochlear mechanics.

Group delays of the DPOAEs with frequencies 2f₁ − f₂, 3f₁ − 2f₂, 4f₁ − 3f₂, and 2f₂ − f₁ were measured in the guinea pig with the phase gradient method. Differences between the f₁- and f₂-sweep paradigm were investigated for the four DPOAEs. The f₂-sweep paradigm yielded larger group delays than the f₁-sweep, but only for the lower sideband DPOAEs (with f_dp < f₁, f₂). The experiments were simulated with a previously developed one-dimensional cochlea model. For the lower sideband DPOAEs, the differences in group delay both across sweep paradigm and across DPOAE components were reproduced by the model. In order to explain the influence of the sweep paradigm on group delay two hypotheses, based on how the DPOAE generation site is affected by the changing primary: the place- and the wave-fixed model, were further developed. The frequency shift invariance of the phase distribution along the basilar membrane was used. The experimental f₁- versus f₂-sweep group delay ratios for the lower sideband DPOAEs appear to be consistent with this theoretical analysis for the wave-fixed hypothesis.

The spacing of threshold microstructure, spontaneous and evoked otoacoustic emissions, reveal characterstics of human cochlear function. Computer models reveal that all these aspects stem from the filtering of a small amount of random variation in the place frequency map of the cochlea. Is this cochlear fine structure unique to humans or is it characteristic of all mammalian ears? This paper presents evidence for cochlear fine structure in chinchillas having spontaneous otoacoustic emissions (SOAEs) in at least one ear. Chinchilla SOAEs are less stable than SOAEs in most human ears, and occur at higher frequecies. The minimal spacing between independent adjacent SOAEs expressed in the distance on the basilar membrane is smaller than humans. DPOAE in chinchillas and kangaroo rats also show fine structure. The spacing is greater than in humans consistent with estimates of shorter round trip travel time in animals with a shorter basilar membrane. This pattern is cosistent with pulsed DPOAE estimates that reveal the response to both components to be shorter than is found in humans. The chinchilla DPOAE measurements are consistent with the predictions of the two source model of DPOAE fine structure. The maxima and minima of the fine structure occurs at the same frequencies for all DPOAEs lower in frequencies than the primaries and is mostly eliminated when the DPOAE frequency is fixed. Group delays of DPOAE obtained with a fixed ratio is modulated by the fine structure in a way consistent with our models and indicate that, in both chinchillas and humans, the component from the dp place can be larger than the component from the generator region.

The medial olivocochlear efferent bundle is the key element of a bilateral efferent reflex activated by sound in either ear and acting directly on cochlear outer hair cells via numerous cholinergic synapses. It may contribute to regulating the mechanical activity of the cochlea. Otoacoustic emissions, being sounds emitted by the cochlea as a reflection of its activity and suppressed by efferent activation, are increasingly considered to be the privileged tool for a noninvasive assessment of the efferent reflex. However, confounding effects on otoacoustic emissions may occur, possibly due to middle-ear muscle reflex activation that shares common features with the efferent one. We report a systematic comparison of the effects on human otoacoustic emissions of efferent activation (by low-level noise in the contralateral ear) vs. various middle-ear manipulations (reflex contractions of the stapedius muscle induced by high-level contralateral noise; moderate middle-ear pressure changes). The profiles of level and phase changes of otoacoustic emissions as a function of frequency proved to be highly specific of the effect at their origin. The changes induced by middle-ear manipulations matched the predictions computed from the standard lumped-element middle-ear model of Zwislocki, with one or two peaks around the resonance frequency(ies) of the involved subsystem, stapes or tympanic membrane. In contrast, the efferent effect was completely different, exhibiting a broadband level suppression associated with a small phase lead. We propose that a careful vector analysis of otoacoustic emission modifications should always enable to identify without ambiguity the contribution of the efferent reflex even when mixed to middle-ear effects, thereby making it more reliable to use otoacoustic emissions as noninvasive probes of efferent olivocochlear function.

Measurements of stimulus-frequency-emission group delay in cats, guinea pigs, and humans provide strong support for the theory of coherent reflection filtering. Application of the theory raises important questions about cochlear tuning and its variation with characteristic frequency and species.

Our previous studies of human interference-response areas (IRAs), from which INFpression tuning curves (STCs) can be extracted, have shown that, for geometric-mean (GM) frequencies of 1 kHz, most ears exhibit considerable enhancement of the 2f₁-f₂ DPOAE above f₂ for L₁/L₂ = 65/55 dB SPL. In contrast, a substantial INFpression above f₂, for a GM of 2 kHz, with L₁=L₂=80 dB SPL, can also be shown. Both these findings imply that important sources of DPOAE generation are located at basilar membrane places located basal to the primary-tone region. However, the classical method used to derive IRAs is not very sensitive to the phases of the multiple sources that contribute to the DPOAE signal. The present study first obtained routine IRAs from 14 normal-hearing humans at these two frequency/level combinations by sweeping the INFpressor or interference tone (IT), i.e., f₃, across the primary-tone space, without regard to phase. The results obtained by this traditional method were compared to IRAs generated by the same two test frequencies and levels based on a phase-sensitive residual technique. In the latter approach, the primary tones were alternatively rotated in phase by 180°, and the f₃ IT by 90°, with the IT being present on every other trial. Such phase rotations resulted in essentially complete cancellation of the primary tones, the IT, and all DPOAEs in the ear-canal signal when n=8 successive trials were averaged. Because the IT was present for one-half the time, when the IT removed a DPOAE source, a residual in the form of a DPOAE signal appeared. Together, these results showed that the shapes of the IRAs were somewhat similar when measured with the traditional versus the residual procedure. However, the phase-sensitive method uncovered larger contributing DPOAE components basal to f₂, as well as the previously documented constituent at the DPOAE place, thus, corroborating other evidence that an additional generation source, basal to f₂ makes a significant contribution to the 2f₁-f₂ DPOAE measured remotely from the ear canal.

Relation between stimulus intensity and 2f1-f2 DPOAE phase was measured. DPOAE phase lag increased when f1 (lower stimulus frequency) was below f2/1.22(f2 means higher stimulus frequency), and DPOAE phase gain increased when f1 was above f2/1.22 as L1 (intensity of f1 tone) increased. This characteristic is similar to that found in the basilar membrane vibration known as “phase-nonlinearity”. This indicates that DPOAE phase reflects the relative phase change of the traveling wave of f1 tone at the DPOAE generator.

Transient evoked otoacoustic emissions, as first reported by D.Kemp in 1978, were simulated in the time domain by a numeric implementation of a realistic model of the human cochlea endowed with forward and reverse middle-ear (ME) impedance. The phenomenon appeared to be not caused by wave reflections at putative basilar membrane (BM) discontinuities, as was often suggested, but to depend rather critically on certain nonlinear properties of cochlear dynamics.

A method is presented to study the generation of intermodulation distortion products (IDPs) in a nonlinear model of the human cochlea in detail. The model used is a simple one-dimensional (long wave) transmission line model, using a simple mass-stiffness-damping combination for the local cochlear partition mechanics. Nonlinearity is introduced in the damping term, causing the generation of IDPs. First it is shown that these IDPs have properties in common with experimental data, measured both psychophysically and in otoacoustic emissions. Although there are clear (quantitative) differences with the experimental data, some of the (qualitative) behavior is similar. The method presented here for studying the generation process in more detail assumes that the total excitation at any section of the model and at a certain (IDP) frequency can be regarded as the sum of contributions from all model sections where distortion generation takes place. The resulting patterns of generated distortion and of contributions to emission and excitation at the characteristic position (DP-place) of the 2f₁-f₂ component explain some of the behavior of this IDP component. It is shown that the generation at the DP-place is influenced by reflection of energy at the stapes boundary, whereas in the case of the emission the phase differences of contributions from the main generation region play a crucial role.

The ability of Wiener series to predict the time course of instantaneous spike rate (as given by the PSTH) in response to a novel stimulus of arbitrary complexity demonstrates that they provide faithful descriptive models of individual auditory nerve fibers–embodying, among other things, the essence of sprectro-temporal filtering. When such models comprise the first three terms of the Wiener series, then background spike rate is represented by the 0^th-order term, linear AC response is represented by the 1^st-order term, and nonlinear AC and DC responses are represented by the 2^nd-order term. Singular-value decomposition can be used to separate the various components of the 2^nd-order term, and to divide its DC response into an excitatory component and an inhibitory component. The inhibitory component typically comprises well-tuned subcomponents that seem clearly to correspond to the phenomena conventionally labeled suppression and adaptation. Both yield negative DC shifts in the instantaneous spike rate. The AC component of the 2^nd-order term imposes even-order nonlinearity on the overall AC response. When combined with the 1^st-order term, it approximates clipping at zero spikes per second when the background spike rate is low, and it embodies the tendency of positive excursions of AC response to be greater than negative excursions even when the background spike rate is sufficient to prevent clipping. For units with best excitatory frequencies that are high, the AC component of instantaneous spike rate becomes vanishingly small. For such units, the 2^nd-order term in the Wiener series embodies the essence of spectro-temporal filtering, both for excitation and for suppression.

We studied cat single auditory-nerve-fiber responses to clicks. Near-threshold responses followed the classic picture of a single resonant system with temporal jitter reducing high-frequency synchrony. At moderate and high levels, there were two separate level-vs-latency regions of non-classic features and phase reversals, each of which is most simply explained as due to two interacting excitation drives. These data indicate that auditory-nerve fibers are excited by the combination, at some stage in the cochlea, of at least three excitation drives that are derived from the acoustic stimulus. One interpretation of these data is that the organ-of-Corti complex vibrates in resonant modes with each mode producing one excitation drive and the mix of modes varying with sound level.

Rate-intensity (RI) functions of single auditory-nerve fibres in the barn owl were well fit by a two-component model which was previously shown to account for the typical features of mammalian RI-functions. All units revealed a compressive nonlinear response component that was restricted to frequencies near the characteristic frequency (CF) and similar to the basilar-membrane characteristic in mammals. It is argued that this provides further evidence for an amplification mechanism increasing sensitivity at low sound levels in birds. A striking difference to mammalian data was that the compressive nonlinearity was not the same for fibres of closely-similar CF in the same individual, but varied with the sensitivity of the fibres. This suggests a more individual, localised amplification effect instead of a global feedback loop uniformly driving all hair cells within a narrow range of CFs.

Action potential generation by the coincidence of bilateral EPSPs or by combination of depolarizing current injection and a unilateral EPSP in nucleus laminaris (NL) neurons was studied in a brainstem slice preparation of chick embryos (E15-20) using the whole cell patch clamp technique. NL neurons are third order auditory neurons and are proposed to behave as coincident detectors concerned with interaural timing discrimination. Coincident or near coincident bilateral excitatory inputs increased the probability of action potential generation (response probability). Local application of GABA (10 μM) reduced the amplitude of EPSPs and shortened the EPSP decay time constant by shunting conductance of postsynaptic GABA_A receptors. Moreover, GABA sharpened the coincidence detection. These results suggest that GABAergic inputs to NL neurons may serve to improve coincidence detection of the bilateral EPSPs through an increase in membrane conductance.

Non-human animals have been reported to posses pitch perception as humans do. We have investigated extraction mechanisms of sequential pitch change in the Japanese monkey (Macaca fuscata). First, neural correlates for the missing fundamental perception were studied in the primary auditory cortex (AI) because previous human data showed that the area around AI appeared to play an essential role in the missing fundamental perception. We found that the AI neurons responded very well to a combination of successive higher harmonics of the fundamental frequency (f0) without f0 itself. However, these AI neurons did not or little responded to each partial of the harmonics. The neurophysiological data basically agreed well with the human psychoacousucal results. Our findings suggested that the pitch perception originated from spectral information and the one created by time information were integrated at or below AI. Next, we stepped into experiments to behaviorally investigate perception of dynamic pitch sequence which is related to music perception and speech communication. The water deprived monkey was trained to discriminate the direction of change in frequency or pitch, rising or falling. Tone bursts and/or complex tone bursts were sequentially presented. After the training, a transfer from sequential tone burst discrimination to sequential pitch discrimination with complex tones was found. The data suggest that the monkey may have a perception for rising pitch and falling pitch similar to humans including the missing fundamental.

Plastic changes in the auditory cortex after deafness were studied in young guinea pigs. Under pentobarbital anesthesia, guinea pigs (150-200 g) were deafened unilaterally or bilaterally by kanamycin (KM). One to 4 months after KM treatment, neural activities of the auditory cortex in response to electrical cochlear stimulation and sound stimulation were measured using optical recording equipment with a 12 × 12 photodiode array and a voltage-sensitive dye (RH795). After 2-4 months of KM treatment, the tonotopic organization became obscure. The distance between active bands in the auditory cortex in response to the 1st- and 2nd-tum stimulation was 710±110μm(n=5) in intact animals, but it was reduced to 120±20 μm (n=3) after 2 months, and 180±110 μm (n=3) after 4 months. The responses to ipsilateral stimuli were augmented after 2-4 months.

Strong SOAEs may be interpreted as sources of internal subthreshold noise. In an earlier study, ears with strong evoked otoacoustic emissions (EOAEs) and SOAEs exhibited higher detection thresholds for empty gaps in low-level wide-band signals than did ears with weak EOAEs and no SOAEs suggesting that internal noise created by the SOAEs masked the gap. The hypothesis of this study was that suppression of internal noise, introduced by filling the gap with a low-level signal, would enhance gap detection in subjects with strong EOAEs. Brief decrements in low-pass (0.1-4 kHz) noise stimuli presented at 10 and 20 dB SL were placed at the stimulus midpoint and their duration was varied adaptively Empty gaps were defined by a period of complete silence. For partially filled gaps, decrement depths of 6 or 10 dB, and 6, 10, or 20 dB were used for the 10-dB and 20-dB SL presentation levels, respectively. Subjects with either strong SOAEs and EOAEs or with no SOAEs and weak EOAEs participated For the empty gaps, the subjects with strong emissions exhibited higher mean gap detection thresholds than did subjects with weak emissions for both presentation levels. Individual data for the empty gaps were compared to those for partially filled gaps with the decrement depth equal to the presentation level. The ears with strong emissions exhibited lower thresholds for the partially filled gaps than for the empty ones; whereas, subjects with weak emissions performed poorer with filled than with empty gaps. The results suggest that strong SOAE activity creates an internal noise that affects the detection of empty gaps in a signal presented near the hearing threshold. When the gap is filled with a low-level signal, SOAEs are suppressed, resulting in improved detection of a brief decrement.

The physiological significance of cochlear efferent system was evaluated by measuring distortion product otoacoustic emissions (DPOAE) and auditory brainstem response (ABR) in guinea pigs. To produce a dysfunction of the cochlear efferent system, we have applied cholinotoxin etylcholine mustard aziridinium ion (AF64-A) into a tiny hole made on the bulla. Animals treated with AF64-A at 100 μM showed a significant decrease in the DPOAE power, while they did not show any statistical differences in the ABR threshold. These results suggest that AF64-A could selectively produce the cochlear efferent dysfunction by irreversibly blocking the choline uptake from the efferent termini without affecting the hair cell - afferent system.

Cisplatin is known to damage the 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. The drug effect took place approximately 25 minutes after intravenous injection of Cisplatin. At the level of reticular lamina, Cisplatin decreased the vibration amplitude around the characteristic frequency. In contrast, the basilar membrane response increased and the tuning became sharper. These changes support the presence of negative feedback in the apical turn of cochlea.

This paper introduces a functional model of auditory sound localization based on the interaural time difference (ITD). The signals in the nervous system such as action potentials and synaptic transmission are modeled computationally and these applied to a coincidence detector circuit model to detect ITD. Then impulse trains fluctuating in time are used as input. The incorporated model outputs a spike histogram of which the peak of the envelope will indicate the ITD. The simulation results show that a peak indication the ITD in the azimuth clearly sharpens when using impulses fluctuating in time as input. This suggests that impulse fluctuation does not behave like noise and it can contribute to the detection of ITDs in the temporally redundant process and the nonlinear output mechanism.

Effect of the basilar membrane (BM) nonlinearities on fine representation of vowel formants of chopper units in the anteroventral cochlear nucleus (AVCN) is investigated using its computational model. A functional model of ventral cochlear nucleus (VCN) units is proposed and evaluated by comparing responses of the model with the physiological data. Rate-place representation of the models to the vowel /ɛ/ is recorded for a wide range of characteristic frequencies (CFs) at both low and high sound levels. Evaluation shows that the model is able to simulate shape of post-stimulus time histogram to short-tone bursts, discharge regularity and phase locking properties of actual chopper units. Simulation using vowel /ɛ/ as stimulus shows that inhibitory inputs from the AN model have effectively suppressed firing rate of the model of VCN units having CF between the first and the second formant of the vowel /ɛ/ at high sound revel only. This results from change of frequency selectivity of the nonlinear BM model related sound level. This rate-place representation is similar to that of actual chopper units in the AVCN. The simulated results suggest that BM-nonlinearities-related sound level play an important role for fine representation of vowel formants of the chopper units in the AVCN. This modeling approach can effectively be applied for a clear representation of speech in the auditory pathway.

There is a general tendency in the literature to assume that the cochlear amplifier only exists in mammals. Although even early data from non-mammalian species show clear evidence of physiological vulnerability of tuning, etc., these phenomena have not been coupled to the existence of a cochlear amplifier. Recent studies of amphibians, reptiles and birds, however, have provided a wealth of evidence that those phenomena in mammals that are attributed to the presence of a cochlear amplifier also exist - usually with identical characteristics - in non-mammals. Thus there is no longer any reason to doubt the importance of cochlear amplification in all land vertebrates.

An estimate of an auditory fiber's time course of instantaneous spike rate (ISR) in response to a novel sound stimulus is given by the peristimulus-time histogram (PSTH) taken over many repetitions of the stimulus. In this paper we address a bullfrog amphibian-papillar (AP) fiber with intermediate BEF. In such units, the PSTH includes both AC and DC responses. We show that the PSTH is predicted by the first three terms of the Wiener series. The first-order term is a component of predicted ISR that is phase locked to the filtered waveform (the output of a linear filter, f₁, whose input was the repeated input waveform). The second-order term yields three subcomponents of predicted ISR: (i) a positive (excitatory) subcomponent that is phase locked to the square of the output of f₁, (ii) a positive subcomponent that is phase locked to the square of the envelope of the output of f₁, and (iii) a negative (inhibitory) subcomponent that is phase locked to the output of another linear filter, f₂, which has a best frequency 250Hz higher than that of f₁. The zero-order term is the background spike rate-a constant. AP fibers exhibit one- and two-tone suppression. The inhibitory subcomponent of the second-order term can be interpreted as describing the effects of such suppression. The first-order term of the Wiener series represents the unclipped AC ISR response to the output of f₁. The first excitatory subcomponent of the second-order term tends to cancel the negative excursions of the first-order term and can be taken to represent clipping of the AC response to the output of f₁ (at zero spike rate). The second excitatory subcomponent represents the DC response to the output of f₁.

Although the frequency separation between the response peaks of the amphibian papilla (AP) and the basilar papilla (BP) in the frog inner ear has been well-documented, the mechanism responsible for such separation remains unclear. While electrical tuning of the hair cells could play a significant role in developing the frequency selectivity displayed by these two organs, the papillar morphologies suggest the existence of some type of mechanical filter that provides the first stage of frequency selectivity. The inner ear morphology dictates that all the energy flowing through each of these organs must pass through its respective contact membrane (CM). Using laser vibrometry we have measured the relative velocity amplitudes of the two CMs as a function of frequency. These measurements show that the APCM velocity is larger than that of the BPCM by more than 15 dB for frequencies below 500 Hz. Above this frequency the velocity of the BPCM increases while the velocity of the APCM decreases creating differences at 1500 Hz of over 10 dB between the two organs. This provides strong evidence supporting the idea of a mechanically-based mechanism underlying energy distribution in the frog inner ear.

Minimum amount of mechanical energy necessary to cause a neuronal spike in the wind receptor cell of cricket is determined at the order of kT (4×10⁻²¹ J at 300°K). The insect mechanoreceptors are therefore facing to the thermal noise of Brownian motion, when working near threshold. The evolution however has achieved a paradoxical solution for sensory signal transmission under the noise problem. Here we show the determination of mechanical energy and the information theoretic analysis on sensory spike trains of the insect mechanoreceptor.

The estimation of the mechanical energy is based on three measurements, deflection sensitivity, sensory threshold, and mechanical resistance of hair support. The deflection sensitivity to air motion was measured by laser-Doppler velocimetry and Gaussian white noise analysis. The mechanical parameters, i.e. the moment of inertia of hair shaft, the spring stiffness of hair support, and the torsional resistance within the support were estimated by applying Stokes' theory for viscous force. Mechanical energy consumed by the resistance provides the maximum estimates of energy available to the receptor cell for stimulus transduction. The energy threshold of the mechanoreceptor is far below that of single photon quantum of visible light (ca. 3×10⁻¹⁹ J). The mechano-receptor is 100 times more sensitive than photoreceptors.

Spike train of the wind receptor cell fluctuates in timing, when responding to weak stimuli near threshold. Simultaneous double recording from two cells revealed that the fluctuations are non-correlated between cells. The receptor array has utilized the cell-intrinsic noise for stochastic sampling of weak sub-threshold signals, and paradoxically improved the detection of signals under the inevitable thermal noise.

The following sections are included:

• Author Index