Unified cochlear model for low- and high-frequency mammalian hearing.

The spatial variations of the intricate cytoarchitecture, fluid scalae, and mechano-electric transduction in the mammalian cochlea have long been postulated to provide the organ with the ability to perform a real-time, time-frequency processing of sound. However, the precise manner by which this tripartite coupling enables the exquisite cochlear filtering has yet to be articulated in a base-to-apex mathematical model. Moreover, while sound-evoked tuning curves derived from mechanical gains are excellent surrogates for auditory nerve fiber thresholds at the base of the cochlea, this correlation fails at the apex. The key factors influencing the divergence of both mechanical and neural tuning at the apex, as well as the spatial variation of mechanical tuning, are incompletely understood. We develop a model that shows that the mechanical effects arising from the combination of the taper of the cochlear scalae and the spatial variation of the cytoarchitecture of the cochlea provide robust mechanisms that modulate the outer hair cell-mediated active response and provide the basis for the transition of the mechanical gain spectra along the cochlear spiral. Further, the model predicts that the neural tuning at the base is primarily governed by the mechanical filtering of the cochlear partition. At the apex, microscale fluid dynamics and nanoscale channel dynamics must also be invoked to describe the threshold neural tuning for low frequencies. Overall, the model delineates a physiological basis for the difference between basal and apical gain seen in experiments and provides a coherent description of high- and low-frequency cochlear tuning.

Cochlear aqueduct revisited: A histological study using human fetuses.

BACKGROUND AND AIM: The cochlear aqueduct (CA) connects between the perilymphatic space of the cochlea and the subarachnoid space in the posterior cranial fossa. The study aimed to examine 1) whether cavitation of the CA occurs on the subarachnoid side or the cochlear side and 2) the growth and/or degeneration of the CA and its concomitant vein. METHODS: We examined paraffin-embedded histological sections from human fetuses: 15 midterm fetuses (crown-rump length or CRL, 39-115 mm) and 12 near-term fetuses (CRL, 225-328 mm). RESULTS: A linear mesenchymal condensation, i.e., a likely candidate of the CA anlage, was observed without the accompanying vein at 9-10 weeks. The vein appeared until 15 weeks, but it was sometimes distant from the CA. At 10-12 weeks, the subarachnoid space (or the epidural space) near the glossopharyngeal nerve rapidly protruded into the CA anlage and reached the scala tympani, in which cavitation was gradually on-going but without epithelial lining. However, CA cavitation did not to occur in the anlage. At the opening to the scala, the epithelial-like lining of the CA lost its meningeal structure. At near-term, the CA was often narrowed and obliterated. CONCLUSION: The CA develops from meningeal tissues when the cavitation of the scala begins. The latter cavitation seemed to reduce tissue stiffness leading, to meningeal protrusion. The so-called anlage of CA might be a phylogenetic remnant of the glossopharyngeal nerve branch. A course of cochlear veins appears to be determined by a rule different from the CA development.

Communication routes between intracranial spaces and inner ear: function, pathophysiologic importance and relations with inner ear diseases.

OBJECTIVE: There exist 3 communication routes between the intracranial space and the inner ear, the vestibular aqueduct, the cochlear aqueduct, and the internal auditory canal. They possess a key role in inner ear pressure regulation and fluid homeostasis and are related to inner ear diseases. REVIEW METHODS: Relevant literature was reviewed, and the current knowledge of the anatomy, physiologic importance, and relations to inner ear diseases were described. Pathologic communication routes such as semicircular canal dehiscence syndrome were highlighted as well. CONCLUSION: Abnormalities in all 3 communication routes may predispose or be the cause of distinct inner ear pathologic condition and involved in other cochlear and vestibular syndromes, in which their role is not completely clear. The increasing knowledge of the underlying mechanisms encourages promising approaches for possible intervention in the future.

Transmission of infrasonic pressure waves from cerebrospinal to intralabyrinthine fluids through the human cochlear aqueduct: Non-invasive measurements with otoacoustic emissions.

The cochlear aqueduct connecting intralabyrinthine and cerebrospinal fluids (CSF) acts as a low-pass filter that should be able to transmit infrasonic pressure waves from CSF to cochlea. Recent experiments have shown that otoacoustic emissions generated at 1kHz respond to pressure-related stapes impedance changes with a change in phase relative to the generator tones, and provide a non-invasive means of assessing intracochlear pressure changes. In order to characterize the transmission to the cochlea of CSF pressure waves due to respiration, the distortion-product otoacoustic emissions (DPOAE) of 12 subjects were continuously monitored around 1kHz at a rate of 6.25epochs/s, and their phase relative to the stimulus tones was extracted. The subjects breathed normally, in different postures, while thoracic movements were recorded so as to monitor respiration. A correlate of respiration was found in the time variation of DPOAE phase, with an estimated mean amplitude of 10 degrees , i.e. 60mm water, suggesting little attenuation across the aqueduct. Its phase lag relative to thoracic movements varied between 0 degrees and -270 degrees . When fed into a two-compartment model of CSF and labyrinthine spaces, these results suggest that respiration rate at rest is just above the resonance frequency of the CSF compartment, and just below the corner frequency of the cochlear-aqueduct low-pass filter, in line with previous estimates from temporal bone and intracranial measurements. The fact that infrasonic CSF waves can be monitored through the cochlea opens diagnostic possibilities in neurology.

Perilymph Kinetics of FITC-Dextran Reveals Homeostasis Dominated by the Cochlear Aqueduct and Cerebrospinal Fluid.

Understanding how drugs are distributed in perilymph following local applications is important as local drug therapies are increasingly used to treat disorders of the inner ear. The potential contribution of cerebrospinal fluid (CSF) entry to perilymph homeostasis has been controversial for over half a century, largely due to artifactual contamination of collected perilymph samples with CSF. Measures of perilymph flow and of drug distribution following round window niche applications have both suggested a slow, apically directed flow occurs along scala tympani (ST) in the normal, sealed cochlea. In the present study, we have used fluorescein isothiocyanate-dextran as a marker to study perilymph kinetics in guinea pigs. Dextran is lost from perilymph more slowly than other substances so far quantified. Dextran solutions were injected from pipettes sealed into the lateral semicircular canal (SCC), the cochlear apex, or the basal turn of ST. After varying delays, sequential perilymph samples were taken from the cochlear apex or lateral SCC, allowing dextran distribution along the perilymphatic spaces to be quantified. Variability was low and findings were consistent with the injection procedure driving volume flow towards the cochlear aqueduct, and with volume flow during perilymph sampling driven by CSF entry at the aqueduct. The decline of dextran with time in the period between injection and sampling was consistent with both a slow volume influx of CSF (~30 nL/min) entering the basal turn of ST at the cochlear aqueduct and a CSF-perilymph exchange driven by pressure-driven fluid oscillation across the cochlear aqueduct. Sample data also allowed contributions of other processes, such as communications with adjacent compartments, to be quantified. The study demonstrates that drug kinetics in the basal turn of ST is complex and is influenced by a considerable number of interacting processes.

Cochlear aqueduct flow resistance depends on round window membrane position in guinea pigs.

The resistance for fluid flow of the cochlear aqueduct was measured in guinea pigs for different positions of the round window membrane. These different positions were obtained by applying different constant pressures to the middle ear cavity. Fluid flow through the aqueduct was induced by small pressure steps superimposed on these constant pressures. It was found that the resistance for fluid flow through the aqueduct depended on the round window position but not on flow direction. The results can be explained by special fibrous structures that connect the round window with the entrance of the aqueduct. It was also found that the equilibrium inner ear pressure depends on middle ear pressure, indicating that the aqueduct does not connect the inner ear with a cavity with constant pressure.

Cochlear aqueduct flow resistance is not constant during evoked inner ear pressure change in the guinea pig.

Inner ear fluid pressure was measured during 6.25 mHz square wave middle ear pressure manipulation, with a perforated tympanic membrane. After a negative-going middle ear pressure change the calculated flow resistance of the inner ear pressure release routes (mainly the cochlear aqueduct) was approximately constant, with a value of 12 Pa s/nl (averaged over two ears), when values for the inner ear window compliance are taken from the literature. After a positive-going middle ear pressure change the calculated flow resistance changed with round window position and with the pressure difference across the cochlear aqueduct. It reached an average maximum value of 114 Pa s/nl. The change of flow resistance during inner ear pressure variation can be explained by a permeability change of the cochlear aqueduct, caused by a change of structures filling the aqueduct and its entrance in scala tympani.

Circadian and menstrual rhythms in frequency variations of spontaneous otoacoustic emissions from human ears.

This paper reports hourly and daily monitoring of the frequencies of spontaneous otoacoustic emissions. Regular circadian variations in frequency were found in two of three subjects. Consistent monthly variations, in step with the menstrual cycle, were seen in three of four women. The circadian cycle typically showed a rise in frequency of 0.6-1% while asleep and a similar fall while awake. The monthly cycle typically saw frequencies rise and fall by 0.4-0.6%, reaching a minimum near the onset of menstruation, and rising to a peak close to ovulation. A review of the literature revealed that certain cardiovascular parameters such as arterial blood pressure follow, over both daily and menstrual cycles, a broadly similar time course to SOAE frequency. Further experiments produced data supporting a relationship between blood pressure and SOAE frequency, and it is therefore suggested that much of the circadian-linked, menstrual-linked, and background variation in SOAE frequency may arise from cardiovascular changes. A likely causal mechanism, involving cerebrospinal fluid, is discussed.

Electrically evoked otoacoustic emissions from apical and basal perilymphatic electrode positions in the guinea pig cochlea.

Stimulation of the cochlea with sinusoidal current results in the production of an otoacoustic emission at the primary frequency of the stimulus current. In this study we test the hypothesis that the wide frequency response from round window (RW) stimulation is due to the involvement of a relatively large spatial segment of the organ of Corti. Tonotopically organized group delays would be evident from perilymphatic electrode locations that restrict the spatial extent of hair cell stimulation. Monopolar and bipolar-paired stimulus electrodes were placed in perilymphatic areas of the first or third cochlear turns and the electrically evoked otoacoustic emissions (EEOAE) produced by these electrodes were compared to that from the RW monopolar electrode in the anesthetized guinea pig. Current stimuli of 35 microA RMS were swept across the frequency range between 60 Hz and 100 kHz. The EEOAE was measured using a microphone coupled to the ear canal. It was found that the bandwidth of EEOAEs from RW stimulation extended to at least 40 kHz and was a relatively insensitive to electrode location on the RW. The group delay of the EEOAE from stimulation at the RW membrane (corrected to stapes motion) was about 53 micros. First and third turn stimulations from electrode placements in perilymph near the bony wall of cochlea yielded narrower band EEOAE magnitude spectra but which had the same short group delays as for RW stimulation. A confined current (from a bipolar electrode pair) applied close to the basilar membrane (BM) in the first turn produced the narrowest frequency-band magnitude emissions and a mean corrected group delay of 176 micros for a location approximately 3 mm from the high frequency end of the BM (corresponding to about the 18 kHz best frequency location). Bipolar electrodes in the third turn scala tympani produced low pass EEOAE magnitude functions with corrected group delays ranging between approximately 0.3 and 1 ms. The average phase slopes did not change with altered cochlear sensitivity and postmortem. These data indicate that the EEOAE from RW stimulation is the summed response from a wide-tonotopic distribution of outer hair cells. A preliminary model study indicates that short time delayed emissions are the result of a large spatial distribution of current applied to perilymphatic locations possibly giving rise to "wave-fixed" emissions.

Notes on the comparative mechanics of hearing. II. On cochlear shunts in birds.

Birds differ in cochlear shunts of acoustic volume flow. One can distinguish three types of shunt: peri-, intra- and intercochlear. The functional significance of shunts is discussed.

Anatomy of the normal human cochlear aqueduct with functional implications.

There is great variation in published descriptions of the shape, size, and patency of the human cochlear aqueduct. The first part of this paper describes the anatomy of the normal human cochlear aqueduct as determined from a study of 101 temporal bones. Nineteen bones aged 0-1 years and approximately 10 bones per decade of life until age 100 years were examined. The aqueduct was found to have a funnel shaped aperture at the cranial end with a dural sheath extending into it for a varying distance. The rest of the aqueduct was filled with a meshwork of loose connective tissue, often with a central lumen within it. Four types of patencies were noted: central lumen patent throughout length of aqueduct (34%), lumen filled with loose connective tissue (59%), lumen occluded by bone (4%), and obliteration of the aqueduct (3%). The mean value (+/- SD) of the narrowest portion was 138 (+/- 58) microns which occurred 200-300 microns from the cochlear end of the aqueduct. There was no correlation between age and narrowest diameter, or between age and category of patency. In the second part of this paper, we propose quantitative models of aqueduct function, based on measurements of ductal dimensions and known acoustical properties of the inner ear. Our model analyses suggest that in normal ears, the aqueduct (1) cannot support fluid flows large enough to explain stapedectomy gushers, (2) does filter out cardiac- and respiration-induced pulses in CSF and prevents them from affecting cochlear function, and (3) has little effect on normal ossicular transmission of sound for frequencies above 20 Hz. In pathological ears, such as those with ossicular disruption or after a type IV tympanoplasty, a patent aqueduct might affect hearing for frequencies below 150 Hz.

Relationships of labyrinthine fluid pressures and blood flow.

Control of labyrinthine blood flow analogous to the autoregulation of cerebral blood flow has been suggested but not experimentally demonstrated. This study concerns the influence of systemic arterial pressure changes on the perilymph and CSF pressures in cats with the cochlear aqueduct (CA) blocked. No direct correlation was found between changes in arterial and CSF pressure. This seemed to be due to the efficient autoregulation of the global cerebral blood flow--a main factor for CSF pressure regulation. The CSF and central venous pressures induced little and much delayed influence on the perilymph pressure when the CA was blocked. However, there was a direct correlation between changes in systemic arterial pressure and the perilymph pressure. This relationship seemed to be mediated via changes in local labyrinthine blood flow. The study indicated a lack of autoregulation of labyrinthine blood flow and a direct correlation between labyrinthine fluid pressure and blood flow when the CA was obstructed.

Pressure gradients affecting the labyrinth during hypobaric pressure. Experimental study.

Hypobaric effects on the perilymph pressure were investigated in 18 cats. The perilymph, tympanic cavity, cerebrospinal fluid, and systemic and ambient pressure changes were continuously recorded relative to the atmospheric pressure. The pressure equilibration of the eustachian tube and the cochlear aqueduct was studied, as well as the effects of blocking these channels. During ascent, the physiologic opening of the eustachian tube reduced the pressure gradients across the tympanic membrane. The patent cochlear aqueduct equilibrated perilymph pressure to cerebrospinal fluid compartment levels with a considerable pressure gradient across the oval and round windows. With the aqueduct blocked, the pressure decrease within the labyrinth and tympanic cavities was limited, resulting in large pressure gradients toward the chamber and the cerebrospinal fluid compartments, respectively. We conclude that closed cavities with limited pressure release capacities are the cause of the pressure gradients. The strain exerted by these pressure gradients is potentially harmful to the ear.

Functional patency of the cochlear aqueduct.

The perilymphatic (PP) and cerebrospinal fluid (PCSF) pressures were investigated in relation to pressure variations in the ear canal, middle ear and intracranial compartment before and after occlusion of the cochlear aqueduct (CA). Experiments using intracranial infusion showed that the CA was responsible for a perfect hydrodynamic balance between the CSF and the perilymph. There are indications of additional pressure release factors but their capacities were not sufficient to prevent the appearance of a longstanding and substantial pressure gradient following occlusion of the CA. A gradual PP build-up, from zero to its original level after the CA was opened and occluded, indicated perilymph production within the labyrinth. Investigation of pressure transfer from the ear canal and middle ear to the perilymph showed that the CA was the major pressure release route from the cochlea. Occlusion of the CA reduced the compliance of the inner ear and severely reduced the pressure release capacity. In such a situation the inner ear is almost incapable of equilibrating ambient pressure changes.

Clinical implications of experiments on alteration of the labyrinthine fluid pressures.

Hearing is affected by changes in hydrostatic pressure of the perilymph, but very high pressures are required to produce a significant loss. Among the observed findings in cats are a rapidly reversible decrease in the sensitivity of the cochlear microphonic that is greater for low frequencies, harmonic distortion and reduction of dynamic range as measured by the input-output function for the cochlear microphonic, and a change in the summating potential from negative to positive. These changes are attributed to a temporary reduction in the size of the cochlear duct due to a shift of water molecules out of the cochlear duct into the blood until the resulting increase in osmotic pressure balances the increase in hydrostatic pressure. Consequently, the organ of Corti is biased "upward" away from the scala tympani. Increasing the hydrostatic pressure of the endolymph produces a "downward" biasing of the organ of Corti and has an opposite effect upon the summating potential. Presumably this is what happens in Meniere's disease. Because of the presence of the perilymphatic canaliculi, the locus of the hydrostatic pressure effect is assumed to be in the region of the reticular lamina. A theory has been developed to explain why cochlear function is very sensitive to relative differences between the hydrostatic pressures of the perilymph and the endolymph but is resistant to large variations in the absolute magnitudes of those pressures. Some of the clinical implications of this theory are discussed.

Dynamics of inner ear pressure change caused by intracranial pressure manipulation in the guinea pig.

Previous studies have shown that pressure changes in the cerebrospinal fluid compartment are transmitted to the inner ear. The main route for pressure transfer is the cochlear aqueduct. about which little is known with regard to its dynamic properties. In the present study, sudden intracranial pressure changes (square waves and short pulses) were created in guinea pigs by means of an electronically controlled infusion system. Simultaneously with pressure manipulation, hydrostatic pressure was monitored in both the peridural space and the perilymphatic compartment of the inner ear. The onset of an inner ear pressure change following manipulation of intracranial pressure was immediate. Inner ear pressure increased or decreased without a measurable time lag, and equalized within a few seconds. During square wave intracranial pressure manipulation, inner ear pressure equalized somewhat more slowly after pressure increase than after pressure decrease. To a first approximation, the pressure equalization curves for the inner ear could be fitted with a single exponential function, rising or falling with a time constant in the range 1-3 s, and the system can be described as a low-pass filter composed of a constant compliance and a constant flow resistance. Detailed analysis, however, showed small deviations from a purely exponential recovery process. With a more complicated (non-linear) model, almost perfect fits to the inner ear pressure equalization curves could be obtained. This non-linearity may be a consequence of the dependence of the compliance and, or flow resistance on pressure.

Direct measurement flow resistance of cochlear aqueduct in guinea pigs.

OBJECTIVE: The cochlear aqueduct connects the scala tympani to the subarachnoid space and is the main pressure equalization canal for the inner ear. Increases in inner ear volume and pressure are thought to cause clinical symptoms such as vertigo, tinnitus and fluctuating hearing loss. In this study the flow resistance of the cochlear aqueduct was determined and its relation with inner ear pressure was studied. MATERIAL AND METHODS: Inner ear pressure was measured in the scala tympani through the round window using a micropipette. Through a second micropipette, artificial perilymph was infused into, or withdrawn from, the scala tympani at various constant rates. From the infusion rate and the change in perilymphatic pressure during infusion the flow resistance of the cochlear aqueduct was calculated. RESULTS: The flow resistance was found not to be constant but to depend on the position of the round window membrane and possibly on the magnitude and direction of fluid flow through the aqueduct. Measured flow resistance values were in the range 11-45 Pa s/nl. For very small flow values the flow resistance averaged over 6 animals was 21 Pa s/nl. CONCLUSIONS: The flow resistance of the cochlear aqueduct is not a constant value. The cochlear aqueduct is a canal with dynamic properties and may play a role in the complicated process of inner ear pressure regulation.

Effects of hypobaric pressure on the labyrinth. Cochlear aqueduct patent.

Cats with the cochlear aqueduct patent were placed in a pressure chamber and exposed for 10 min to hypobaric pressures of 5.1 and 6.8 kPa relative to atmospheric pressure. The experiments were designed according to a program used for treatment of Meniere's disease. The perilymph, middle ear, cerebrospinal fluid (CSF), venous, arterial and chamber pressures were recorded. The results demonstrated that hypobaric effects on the labyrinth were mediated via pressure changes in the middle ear and not via a systemic vascular or CSF influence. A reduction in chamber pressure induced a relative increase in middle ear pressure. It was the rate of the hypobaric change as well as the patency of the cochlear aqueduct and the Eustachian tube function that determined the magnitude of the initial perilymph peak pressure and the duration of this pressure increase. A rapid versus a slow rate induced an initial perilymph increase of 3.4 and 2.2 kPa, respectively. This relative pressure increase was eliminated within 1 min via the patent aqueduct. Thus, neither did a longstanding perilymph pressure increase occur during the hypobaric exposure, nor did a prolonged significant reduction in perilymph pressure occur after atmospheric pressure was restored.

Transmission of complex pressure waves through the perilymphatic fluid in cats.

The response of the perilymphatic fluid to complex pressure waves, composed of low-frequency sine waves superimposed on square-wave pressure pulses of varying amplitude was studied. In cats with a patent cochlear aqueduct a pronounced positive pressure change could be induced in the perilymphatic fluid when complex pressure waves were used. The time constants associated with the stabilization of the perilymphatic pressure after the application of pressure complexes were longer than those associated with square-wave pulses alone. The results indicate that the functional patency of the cochlear aqueduct could be influenced by the transmission of complex pressure waves. The results also indicate that when trying to influence the inner ear hydrodynamic balance in patients with Meniere's disease, the effect of complex pressure waves is far superior to the effect of square-wave pressure pulses in patients with an open cochlear aqueduct.

Transmission of square wave pressure pulses through the perilymphatic fluid in cats.

The inner ear hydrodynamics have been studied in a series of experiments on cats. A detailed analysis has been made of the perilymphatic pressure response to square wave pressure pulses applied to the ear canal and middle ear. It was found that the initial pressure response was followed by a rebound pressure response of the opposite phase. It was also found that in most cases each phase of the pressure response could be expressed in terms of two time constants. When the cochlear aqueduct was patent, the perilymphatic pressure response showed almost equal positive and negative pressure changes. However, when the cochlear aqueduct was surgically blocked, the perilymphatic pressure response consisted almost exclusively of the first phase of the response, while the rebound phase disappeared almost completely. The possibility of influencing the inner ear fluid balance in Meniere's disease by external pressure changes is discussed in the light of the present experimental results.