Frequency Shifts in a Local Oscillator Model for the Generation of Spontaneous Otoacoustic Emissions by the Lizard Ear.

INTRODUCTION: In order to understand human hearing, it helps to understand how the ears of lower vertebrates, like, for instance, lizards, function. A key feature in common is that the ears of both humans and lizards emit faint, pure tones known as spontaneous otoacoustic emissions (SOAEs). More than four decades after their discovery, the mechanism underlying these emissions is still imperfectly understood, although it is known that they are important for improving the sensitivity and sharpness of hearing. In both humans and lizards, the frequencies of SOAEs change by a few percent when static pressure is applied to the tympanic membrane. For the human ear, this observation is normally explained by a so-called global oscillator model (such as with Shera's coherent reflection model), in which the emissions result from standing waves, and external pressure changes the boundary conditions - the stiffness of the oval and round windows - which then has a global effect on the SOAE frequencies. METHODS: Here we investigate how changing parameters of an earlier developed local oscillator model for the lizard ear can change the frequencies of the SOAEs. A major feature of the model is that each oscillator is coupled only to its immediate neighbours. The oscillators then cluster into groups of identical frequency, and each of these so-called frequency plateaus can be taken to represent an SOAE. RESULTS: Even though the natural (unperturbed) frequencies of all the oscillators remain fixed, here we find for several model parameters that by slightly changing their value the frequency plateaus - the SOAEs - shift by a few percent. Plots of how these changes alter SOAE frequencies are given, and their magnitude corresponds well with observations of SOAE changes in lizards. DISCUSSION: Investigation of the influence of the change of parameters in an earlier developed local oscillator model for the lizard ear shows that a local oscillator model can explain small SOAE frequency changes as well as a global oscillator model.

Analysis of an impulse response measured at the basilar membrane of the chinchilla.

In a recent paper [J. Acoust. Soc. Am. 133, 2224-2239 (2013)], Shera and Cooper report on the impulse response of the basilar membrane (BM) of a chinchilla, a waveform which shows repetitive bursts. They explain the bursts in terms of repeated coherent reflection at BM discontinuities and partial reflection at the stapes ("coherent reflection filtering"). Here the same waveform is examined in detail, highlighting features which indicate that the coherent reflection model, with calls for the same repetitive process to act on each successive burst, does not fully account for the shape of the measured impulse response.

Something in Our Ears Is Oscillating, but What? A Modeller's View of Efforts to Model Spontaneous Emissions.

When David Kemp discovered "spontaneous ear noise" in 1978, it opened up a whole new perspective on how the cochlea works. The continuous tonal sound emerging from most healthy human ears, now called spontaneous otoacoustic emissions or SOAEs, was an unmistakable sign that our hearing organ must be considered an active detector, not just a passive microphone, just as Thomas Gold had speculated some 30 years earlier. Clearly, something is oscillating as a byproduct of that sensitive inbuilt detector, but what exactly is it? Here, we give a chronological account of efforts to model SOAEs as some form of oscillator, and at intervals, we illustrate key concepts with numerical simulations. We find that after many decades there is still no consensus, and the debate extends to whether the oscillator is local, confined to discrete local sources on the basilar membrane, or global, in which an assembly of micro-mechanical elements and basilar membrane sections, coupled by inner ear fluid, interact over a wide region. It is also undecided whether the cochlear oscillator is best described in terms of the well-known Van der Pol oscillator or the less familiar Duffing or Hopf oscillators. We find that irregularities play a key role in generating the emissions. This paper is not a systematic review of SOAEs and their properties but more a historical survey of the way in which various oscillator configurations have been applied to modelling human ears. The conclusion is that the difference between the local and global approaches is not clear-cut, and they are probably not mutually exclusive concepts. Nevertheless, when one sees how closely human SOAEs can be matched to certain arrangements of oscillators, Gold would no doubt say we are on the right track.

Hydrostatic fluid pressure in the vestibular organ of the guinea pig.

Since inner ear hair cells are mechano-electric transducers the control of hydrostatic pressure in the inner ear is crucial. Most studies analyzing dynamics and regulation of inner ear hydrostatic pressure performed pressure measurements in the cochlea. The present study is the first one reporting about absolute hydrostatic pressure values in the labyrinth. Hydrostatic pressure of the endolymphatic system was recorded in all three semicircular canals. Mean pressure values were 4.06 cmH(2)O ± 0.61 in the posterior, 3.36 cmH(2)O ± 0.94 in the anterior and 3.85 cmH(2)O ± 1.38 in the lateral semicircular canal. Overall hydrostatic pressure in the vestibular organ was 3.76 cmH(2)O ± 0.36. Endolymphatic hydrostatic pressure in all three semicircular canals is the same (p = 0.310). With regard to known endolymphatic pressure values in the cochlea from past studies vestibular pressure values are comparable to cochlear values. Until now it is not known whether the reuniens duct and the Bast's valve which are the narrowest passages in the endolymphatic system are open or closed. Present data show that most likely the endolymphatic system is a functionally open entity.

Are human spontaneous otoacoustic emissions generated by a chain of coupled nonlinear oscillators?

Spontaneous otoacoustic emissions (SOAEs) are generated by self-sustained cochlear oscillators. Properties of a computational model for a linear array of active oscillators with nearest neighbor coupling are investigated. The model can produce many experimentally well-established properties of SOAEs.

A model for the relation between stimulus frequency and spontaneous otoacoustic emissions in lizard papillae.

Spontaneous otoacoustic emissions (SOAEs) and stimulus frequency otoacoustic emissions (SFOAEs) have been described from lizard ears. Although there are several models for these systems, none has modeled the characteristics of both of these types of otoacoustic emissions based upon their being derived from hair cells as active oscillators. Data from the ears of two lizard species, one lacking a tectorial membrane and one with a chain of tectorial sallets, as described by Bergevin et al. ["Coupled, active oscillators and lizard otoacoustic emissions," AIP Conf. Proc. 1403, 453 (2008)], are modeled as an array of coupled self-sustained oscillators. The model, originally developed by Vilfan and Duke ["Frequency clustering in spontaneous otoacoustic emissions from a lizard's ear," Biophys. J. 95, 4622-4630 (2008)], well describes both the amplitude and phase characteristics of SFOAEs and the relation between SFOAEs and SOAEs.

Modulation of Vestibular Microphonics: A Historical Note.

Modulation of microphonics has recently been used to investigate the sensitivity of the utricle in the vestibular organ of the guinea pig. The same technique was used more than 30 years ago to obtain information on the processing of rotational stimuli in the horizontal semicircular canals of the pigeon. Data from that time were reanalysed to give a relation that describes the mechano-electrical transduction (MET) process in vestibular hair cells.

Modeling the characteristics of spontaneous otoacoustic emissions in lizards.

Lizard auditory papillae have proven to be an attractive object for modelling the production of spontaneous otoacoustic emissions (SOAE). Here we use an established model (Vilfan and Duke, 2008) and extend it by exploring the effect of varying the number of oscillating elements, the strength of the parameters that describe the coupling between oscillators, the strength of the oscillators, and additive noise. The most remarkable result is that the actual number of oscillating elements hardly influences the spectral pattern, explaining why spectra from very different papillar dimensions are similar. Furthermore, the spacing between spectral peaks primarily depends on the reactive coupling between the oscillator elements. This is consistent with observed differences between lizard species with respect to tectorial covering of hair cells and SOAE peak spacings. Thus, the model provides a basic understanding of the variation in SOAE properties across lizard species.

Intratympanic gentamicin therapy for control of vertigo in unilateral Menire's disease: a prospective, double-blind, randomized, placebo-controlled trial.

CONCLUSIONS: Intratympanic application of gentamicin is a relatively safe and efficient treatment for the reduction of complaints of vertigo attacks associated with Menière's disease. The treatment also reduces the severity of the perceived aural fullness. OBJECTIVE: To investigate the effectiveness of intratympanic gentamicin treatment in patients with unilateral Menière's disease. SUBJECTS AND METHODS: In a prospective, double-blind, randomized, placebo-controlled clinical trial subjects scored vertigo complaints, aural fullness and tinnitus, before, during and up to 1 year after treatment. Hearing loss was monitored with pure tone audiometry. RESULTS: Gentamicin treatment resulted in a significant reduction of the score for vertigo complaints and the score for perceived aural fullness. A small increase in hearing loss (average 8 dB) was measured in the gentamicin group.

Cochlear impulse responses resolved into sets of gammatones: the case for beating of closely spaced local resonances.

Gammatones have had a long history in auditory studies, and recent theoretical work suggests they may play an important role in cochlear mechanics as well. Following this lead, the present paper takes five examples of basilar membrane impulse responses and uses a curve-fitting algorithm to decompose them into a number of discrete gammatones. The limits of this 'sum of gammatones' (SOG) method to accurately represent the impulse response waveforms were tested and it was found that at least two and up to six gammatones could be isolated from each example. Their frequencies were stable and largely independent of stimulus parameters. The gammatones typically formed a regular series in which the frequency ratio between successive members was about 1.1. Adding together the first few gammatones in a set produced beating-like waveforms which mimicked waxing and waning, and the instantaneous frequencies of the waveforms were also well reproduced, providing an explanation for frequency glides. Consideration was also given to the impulse response of a pair of elastically coupled masses-the basis of two-degree-of-freedom models comprised of coupled basilar and tectorial membranes-and the resulting waveform was similar to a pair of beating gammatones, perhaps explaining why the SOG method seems to work well in describing cochlear impulse responses. A major limitation of the SOG method is that it cannot distinguish a waveform resulting from an actual physical resonance from one derived from overfitting, but taken together the method points to the presence of a series of closely spaced local resonances in the cochlea.

Evaluation of low-frequency biasing as a diagnostic tool in Menière patients.

Although it is generally accepted that endolymphatic hydrops is the cause of complaints in patients suffering from Menière's disease, it has not been possible up to now to prove the presence of an endolymphatic hydrops in living humans. This study evaluated the psychophysical method introduced by Mrowinski et al. [Mrowinski D., Gerull G., Nubel K., Scholz G., 1995. Masking and pitch shift of tone bursts and clicks by low-frequency tones. Hear. Res. 85, 95-102; Mrowinski D., Scholz G., Krompass S., Nubel K., 1996. Diagnosis of endolymphatic hydrops by low-frequency masking. Audiol. Neurootol. 1, 125-134] to diagnose endolymphatic hydrops. These authors used low frequency biasing to differentiate between individuals with and individuals without Menière's disease. In the present study no statistically significant differences in masking parameters could be found between a large number (n=91) of ears with Menière's disease and ears (n=52) with comparable sensorineural hearing losses, but without symptoms of Menière's disease. Our results support the idea that results deviating from normal in low frequency biasing measurements are not due to endolymphatic hydrops itself, but to other pathological changes of the inner ear. An explanation could be that with increasing hearing loss the gain of the cochlear amplifier decreases, leading to smaller modulation depths.

Hippocampal volume measurement in patients with Ménière's disease: a pilot study.

CONCLUSION: No signs of chronic stress as in hippocampal atrophy were present in patients with Ménière's disease. OBJECTIVE: To evaluate the effect of chronic stress (allostatic load) by measuring hippocampal volume in patients with Ménière's disease. SUBJECTS AND METHODS: Ten patients with Meniere's disease and 10 healthy controls were evaluated for absolute and relative hippocampal volumes measured on MRI scans, saliva cortisol levels and frequency of daily stressors. The study was performed in a prospective, controlled setting with two raters who were blinded as to subject identity. RESULTS: Saliva cortisol levels and presence of daily stressor scores were similar in both groups. The first rater measured mean hippocampal volumes of 2.80 +/- 0.36 cm3 vs 3.15 +/- 0.52 cm3 (right) and 2.49 +/- 0.32 cm3 vs 3.06 +/- 0.46 cm3 (left), for the Ménière's disease and control group, respectively. The second rater measured 3.44 +/- 0.35 cm3 vs 3.60 +/- 0.52 cm3 (right) and 3.00 +/- 0.40 cm3 vs 3.42 +/- 0.45 cm3 (left), respectively. The volume of the left hippocampus was significantly smaller in patients with Ménière's disease compared with the controls for both raters (p < 0.05) and the right hippocampal volume was not different between the two groups. With correction for variation in head size (partial brain and partial intracranial volume) no significant differences in relative hippocampal volumes were observed between patients with Ménière's disease and the control group.

A simple model for the generation of the vestibular evoked myogenic potential (VEMP).

OBJECTIVE: To describe the mechanism by which the vestibular evoked myogenic potential is generated. METHODS: Vestibular evoked myogenic potential generation is modeled by adding a large number of muscle motor unit action potentials. These action potentials occur randomly in time along a 100 ms long time axis. But because between approximately 15 and 20 ms after a loud short sound stimulus (almost) no action potentials are generated during VEMP measurements in human subjects, no action potentials are present in the model during this time. RESULTS: The evoked potential is the result of the lack of amplitude cancellation in the averaged surface electromyogram at the edges of this 5 ms long time interval. CONCLUSIONS: The relatively simple model describes generation and some properties of the vestibular evoked myogenic potential very well. SIGNIFICANCE: It is shown that, in contrast with other evoked potentials (BAEPs, VERs), the vestibular evoked myogenic potential is the result of an interruption of activity and not that of summed synchronized neural action potentials.

The ordering of milestones in language development for children from 1 to 6 years of age.

PURPOSE: To scale language milestones in a group of 527 children to provide an instrument for screening language development. Procedure The questionnaire regarding these milestones was completed by parental report. It was evaluated whether the scaled milestones satisfied the assumptions of the Mokken item response model. RESULTS: The scalability of the final scale of 14 milestones was strong (H = .95), its reliability was high (rho = .96), and it satisfied the assumptions of the Mokken model. CONCLUSIONS: A single, unidimensional scale of diverse milestones was developed. It taps lexical, syntactic, and phonological skills, as well as both receptive and expressive language skills, and is well suited for mapping progress in language ability.

Analysis of cortisol and other stress-related hormones in patients with Ménière's disease.

OBJECTIVE: To evaluate cortisol and catecholamine levels in patients with Ménière's disease. STUDY DESIGN: Prospective, controlled study. SETTING: Tertiary referral center. PATIENTS: Thirty patients with Ménière's disease and 18 healthy controls. MAIN OUTCOME MEASURES: Serum and saliva cortisol, serum cortisol after the dexamethasone suppression test, urine free cortisol, and urine catecholamines. RESULTS: The serum and saliva cortisol levels were higher in Ménière's patients compared with their control group: 440 +/- 127 (n = 28) versus 366 +/- 90 (nmol/L) (n = 18) and 17.2 +/- 6.1 (n = 18) versus 11.6 +/- 4.6 (nmol/L) (n = 9), respectively. Both differences were significant (p < 0.05). There were no dissimilarities in urine cortisol or urine catecholamines for either group. Twenty-eight Ménière's patients were divided into two subgroups, namely, high- and low-cortisol groups, using a serum cortisol level cutoff point of 465 nmol/L (median). The total Ménière's disease time and the duration of tinnitus tended to be longer in the high-cortisol group (p = 0.07, two-tailed). The total Ménière's disease time was 13.5 +/- 9.9 years in the high-cortisol group and 7.1 +/- 7.4 years in the low-cortisol group (n = 14 for both). The subgroups were matched for age, gender, and unilaterally or bilaterally affected ears. CONCLUSION: Patients with Ménière's disease have higher serum cortisol levels. It is suggested that these higher cortisol levels are rather the result than the cause of this chronic disease, because patients affected longer seem to have higher cortisol levels. The exact impact of these higher cortisol levels on the inner ear and endolymph homeostasis is yet unknown.

The vibrating reed frequency meter: digital investigation of an early cochlear model.

The vibrating reed frequency meter, originally employed by Békésy and later by Wilson as a cochlear model, uses a set of tuned reeds to represent the cochlea's graded bank of resonant elements and an elastic band threaded between them to provide nearest-neighbour coupling. Here the system, constructed of 21 reeds progressively tuned from 45 to 55 Hz, is simulated numerically as an elastically coupled bank of passive harmonic oscillators driven simultaneously by an external sinusoidal force. To uncover more detail, simulations were extended to 201 oscillators covering the range 1-2 kHz. Calculations mirror the results reported by Wilson and show expected characteristics such as traveling waves, phase plateaus, and a response with a broad peak at a forcing frequency just above the natural frequency. The system also displays additional fine-grain features that resemble those which have only recently been recognised in the cochlea. Thus, detailed analysis brings to light a secondary peak beyond the main peak, a set of closely spaced low-amplitude ripples, rapid rotation of phase as the driving frequency is swept, frequency plateaus, clustering, and waxing and waning of impulse responses. Further investigation shows that each reed's vibrations are strongly localised, with small energy flow along the chain. The distinctive set of equally spaced ripples is an inherent feature which is found to be largely independent of boundary conditions. Although the vibrating reed model is functionally different to the standard transmission line, its cochlea-like properties make it an intriguing local oscillator model whose relevance to cochlear mechanics needs further investigation.

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.

Quantification of audiogram fine-structure as a function of hearing threshold.

We investigated the amount of fine-structure in the audiograms of patients with Menière's disease. Both ears (often an affected and an unaffected ear) were investigated. Data are presented from 39 ears of 21 patients with hearing thresholds varying from about 0 to 70 dB HL. The fine-structure was measured in the frequency range from 500 to 3500 Hz; this agrees with a part of the basilar membrane from 10 to 22.5 mm from the apex. The fine-structure was characterized by means of the number of peaks N(p) and the sum S(p) of the heights of all the peaks in an audiogram. From these quantities, we also determined average peak height H(p). We found a negative correlation between hearing loss and strength of fine-structure, i.e. the higher the thresholds the smaller N(p) and S(p) as well as H(p). Also N(p) and H(p) were correlated, i.e. the more peaks the higher the average peak height. The summated peak height S(p)=N(p)H(p) showed a strong dependence on the hearing loss. In cases of strong fine-structure, S(p) reached values around 200 dB.

Evaluation of cochlear function in an acute endolymphatic hydrops model in the guinea pig by measuring low-level DPOAEs.

During and after microinjection of artificial endolymph into scala media of the guinea pig, the 2f1- f2 -DPOAE at 4.5 kHz generated by low-level primaries was recorded. Reproducible changes were measured when 1.1 microl of artificial endolymph was injected at a rate of 1.65 nl/s (1.53-1.83). This volume corresponds with an acute endolymphatic hydrops of 23%. After the onset of injection the inner ear pressure immediately increased to a mean higher level of 22 Pa, whereas the 2f1- f2 -amplitude and -phase did not change for about 1 min. Thereafter, the amplitude decreased 2.6 dB (+/- 0.7) on average and slowly regained almost its initial value, with recovery frequently starting within the period of injection. In an attempt to explain the observed changes in 2f1- f2 -amplitude the basilar membrane displacement towards scala tympani at the 2f1- f2 generation site is estimated to be 19 nm for a 1.1 microl increase of endolymph volume. A small deflection of the outer hair cell stereocilia and as a consequence a change in cell conductance may explain the 2f1- f2 -amplitude changes. However, the precise mechanism of cochlear function change caused by endolymph volume increase (hydrops) remains to be elucidated.