F2 Distortion Product Otoacoustic Emissions Research Articles

Otoacoustic emissions and contralateral suppression in tinnitus sufferers with normal hearing

BackgroundThe general consensus on the role of hearing loss in generating tinnitus is not relevant in tinnitus patients with normal hearing thresholds. One source of tinnitus may be related to damage to outer hair cells (OHC) of the cochlea. If the OHC of the human cochlea are to be involved in the generation of tinnitus, testing of Otoacoustic emissions (OAE) could provide a reliable means of recording OHC dysfunction. We investigated the role of OHC and cochlear efferent system in tinnitus development in normal hearing ears through studying of Distortion Product Otoacoustic Emissions (DPOAE) and Transient Evoked Otoacoustic Emissions (TEOAE) amplitudes, contralateral suppression amplitudes and suppression value in 15 normal hearing tinnitus patients and 15 control subjects.ResultsMean f2 DPOAE amplitudes and contralateral suppression were significantly lower in tinnitus group compared to controls for all frequencies from 1001 to 6348 Hz. Suppression values of DPOAEs revealed lower but not significant difference between tinnitus and control groups for all frequencies except 1587 and 6348 Hz. TEOAE amplitudes and contralateral suppression were significantly lower in tinnitus groups for all frequencies from 1000 to 4000 Hz compared to the control group. Suppression value of TEOAEs revealed no significant difference between the two groups for all frequencies except 3000 and 4000 Hz were significantly lower in the tinnitus group compared to the control group.ConclusionsNormal hearing manifested by pure tone audiometry in non-vascular tinnitus sufferers does not exclude OHC and/or cochlear efferent pathology.

Long-term moderate noise exposure enhances the medial olivocochlear reflex

ObjectiveTo investigate the effects of long-term moderate noise on hearing functions, MOCR, and MEMR. MethodsMice were exposed to the moderate noise (11.2 – 22.4 kHz, 80 dB SPL, 6 h/day, 4 weeks). Subsequently, the hearing functions, including threshold and input-output roles of ABR (auditory brainstem response) and cubic (2f1–f2) DPOAEs (distortion product otoacoustic emissions) were evaluated. Also, MEMR and MOCR were assessed shortly after or at four weeks following the termination of exposure to the noise. ResultsThe mice's acoustic suppression reflex was strengthened, hearing functions and MEMR were unaffected four weeks after the moderate noise. For primary tones of 16, 20 and 24 kHz, the strengths of contralateral and ipsilateral suppression in the noise group were about double those recorded in the control group. In order to further determine whether the functional changes of the afferent or efferent nerves increased the strengths of acoustic suppression, the mouse's left ear was inserted the earplug, and then exposed the moderate noise for four weeks. The strengths of contralateral suppression at 16, 20 and 24 kHz were increased for the noise + earplug than for the control group and were indistinguishable between the noise + earplug and the noise group. While no significant changes were found in the strengths of ipsilateral suppression at all frequencies for the noise + earplug group compared with the control group. Under ketamine/xylazine anesthesia, the broadband suppressor noise did not stimulate the MEMR by 20 min post-induction at all frequencies in three groups. ConclusionOur data demonstrated that the long-term moderate noise-exposure strengthened mice's MOCR by changing its afferent nerves, and unaffected cochlear hair cells and type I spiral ganglion neurons.

Paired measurements of cochlear function and hair cell count in Dutch-belted rabbits with noise-induced hearing loss

The effects of noise-induced hearing loss have yet to be studied for the Dutch-belted strain of rabbits, which is the only strain that has been used in studies of the central auditory system. We measured auditory brainstem responses (ABRs), 2f1−f2 distortion product otoacoustic emissions (DPOAEs), and counts of cochlear inner and outer hair cells (IHCs and OHCs, respectively) from confocal images of Myo7a-stained cochlear whole-mounts in unexposed and noise-overexposed, Dutch-belted, male and female rabbits in order to characterize cochlear function and structure under normal-hearing and hearing-loss conditions. Using an octave-band noise exposure centered at 750 Hz presented under isoflurane anesthesia, we found that a sound level of 133 dB SPL for 60 min was minimally sufficient to produce permanent ABR threshold shifts. Overexposure durations of 60 and 90 min caused median click-evoked ABR threshold shifts of 10 and 50 dB, respectively. Susceptibility to overexposure was highly variable across ears, but less variable across test frequencies within the same ear. ABR and DPOAE threshold shifts were smaller, on average, and more variable in male than female ears. Similarly, post-exposure survival of OHCs was higher, on average, and more variable in male than female ears. We paired post-exposure ABR and DPOAE threshold shift data with hair cell count data measured in the same ear at the same frequency and cochlear frequency location. ABR and DPOAE threshold shifts exhibited critical values of 46 and 18 dB, respectively, below which the majority of OHCs and IHCs survived and above which OHCs were wiped out while IHC survival was variable. Our data may be of use to researchers who wish to use Dutch-belted rabbits as a model for the effects of noise-induced hearing loss on the central auditory system.

Investigation of the 2f1−f2 and 2f2−f1 distortion product otoacoustic emissions using a computational model of the gerbil ear

In this work, a three-dimensional computational model of the gerbil ear is used to investigate the generation of the 2f1−f2 and 2f2−f1 distortion product otoacoustic emissions (DPOAEs). In order to predict both the distortion and reflection sources, cochlear roughness is modeled by introducing random inhomogeneities in the outer hair cell properties. The model was used to simulate the generation of DPOAEs in response to a two-tone stimulus for various primary stimulus levels and frequency ratios. As in published experiments, the 2f1−f2 DPOAEs are mostly dominated by the distortion component while the 2f2−f1 DPOAEs are dominated by the reflection component; furthermore, the influence of the levels and frequency ratio of the primaries are consistent with measurements. Analysis of the intracochlear response shows that the distortion component has the highest magnitude at all longitudinal locations for the 2f1−f2 distortion product (DP) while the distortion component only dominates close to the DP best place in the case of the 2f2−f1 DP. Decomposition of the intracochlear DPs into forward and reverse waves demonstrates that the 2f1−f2 DP generates reverse waves for both the distortion and reflection components; however, a reverse wave is only generated for the reflection component in the case of the 2f2−f1 DP. As in experiments in the gerbil, the group delay of the reflection component of the DPOAE is between 1× and 2× the forward group delay, which is consistent with the propagation of DP towards the stapes as slow reverse waves.

Negative Middle Ear Pressure and Composite and Component Distortion Product Otoacoustic Emissions.

Distortion product otoacoustic emissions (DPOAEs), a by-product of normal outer hair cell function, are used in research and clinical settings to noninvasively test cochlear health. The composite DPOAE recorded in the ear canal is the result of interactions of at least two components: a nonlinear distortion component (the generator component) and a linear reflection component. Negative middle ear pressure (NMEP) results in the tympanic membrane being pulled inward and increases middle ear impedance. This influences both the forward travel of stimuli used to induce distortion products and the reverse travel of the emissions back to the ear canal. NMEP may therefore limit the effectiveness of DPOAEs in clinical settings. Twenty-six normal-hearing subjects were recruited, and eight were able to reliably and consistently induce NMEP using the Toynbee maneuver. Eight interleaved measures of tympanic peak pressure (TPP) were collected for each subject at normal pressure and NMEP. DPOAEs were then collected both when middle ear pressure was normal and during subject-induced NMEP. All measures were interleaved. Two primary tones were swept logarithmically across frequency (1 second per octave) from f1 = 410 to 6560 Hz and f2 = 500 to 8000 Hz (f1/f2 = 1.22), producing 2f1 - f2 DPOAEs from 320 to 5120 Hz. DPOAEs were collected at three equal-level primary level combinations (L65, L70, L75 dB SPL). Before composite and component DPOAE analysis, analysis of the f1 DPOAE primary confirmed that subjects had successfully induced NMEP. DPOAE and component magnitudes were separately analyzed using repeated measures analysis of variances with three factors, primary level (L65, L70, L75 dB SPL), middle ear pressure (normal pressure versus NMEP), and frequency (500 to 4000 Hz). Mean subject-induced NMEP ranged from -65 to -324 daPa. Changes in the magnitude (dB) of the primary tones used to induce the DPOAE provided a reliable indicator of subject-induced NMEP. Composite DPOAE and component levels were significantly affected by NMEP for all the frequencies tested. Changes were most clearly observed for the generator component with one subject demonstrating a mean decrease of 12 dB in magnitude during NMEP. Results were subject-specific, and there was a correlation between the degree of negative TPP induced and the amount of change in DPOAE level. Mean TPPs collected during NMEP ranged from -65 to -324 daPa and significantly affected composite DPOAE, generator, and reflection component levels. Changes in the magnitude of the swept-primaries as a function of frequency were used to confirm that NMEP had been successfully induced. The patterns of change in the composite DPOAEs were clearer and easier to interpret when the components of the DPOAE were separated with evaluation of the generator component alone.

Complex level alterations of the 2f1–f2 distortion product due to hypoxia

For diagnostic purposes and a better understanding of the pathophysiology of inner ear hearing disorders it would be of great interest to have parameters available that indicate inner ear hypoxia. In animal studies typical hypoxia-related alterations of the 2f1-f2 distortion product otoacoustic emissions (DPOAE) such as a reversible level decrease and destabilization could be demonstrated. The goal of this study was to investigate whether these hypoxia-associated alterations can also be observed in humans because this might help develop a new diagnostic tool for patients with inner ear disorders. In 16 volunteers DPOAE levels were continuously measured at first under normal room air conditions, during and after 8.5h of oxygen deprivation (13% O2) and during re-oxygenation. Saturation of oxygen of arterial blood (SaO2) was monitored. The mean SaO2 during the hypoxic interval was 78%. A significant decrease in DPOAE level under hypoxia occurred in five different test persons at one or more frequencies (f2=1, 1.5, 2, 3, and 4kHz). A destabilization of the DPOAE level with considerable fluctuations during hypoxia was observed in nine subjects at one or more frequencies. Furthermore, the so called 'post hypoxia effect' could be observed in five participants. The observations made here have been described similarly in animal studies and seem to be characteristic of metabolic disorders of the cochlea caused by hypoxia. To our knowledge, this is the first study to examine DPOAE level alterations over time in humans under conditions of normobaric hypoxia. If DPOAE destabilization is observed in a clinical setting in patients with certain inner ear hearing disorders hypoxia can be suspected as one underlying pathophysiological cause which might influence treatment decisions.

Can cochlear mechanics contribute to amplitude modulation perception?

Amplitude modulation (AM) detection has been successfully used as a psychophysical measure of auditory temporal processing. Our understanding of the role of the auditory periphery in processing AM signals is emerging through physiological and psychophysical studies. Unfortunately, direct physiological estimates of the cochlea’s mechanical response to AM signals are not obtainable in humans. This study tries to fill this critical gap in knowledge by exploring the relationship between perception (through psychophysical AM detection) and mechanics (through otoacoustic emissions). Psychometric function for AM perception was measured for a 2-kHz carrier frequency and 10-Hz modulation frequency (fm). Distortion product otoacoustic emissions (DPOAEs) were recorded with amplitude-modulated f1 with fm = 10 Hz and steady-state f2. The frequencies of f1 and f2 were chosen to yield a 2f1 − f2 DPOAE around 2 kHz near a peak in the fine structure. The ratio between the DPOAE pressure at 2f1 − f2 and that of the sidebands separated by fm (AMOAE depth) was calculated as a function of different modulation depths. Results indicate that there might be a correlation between AM perception performance and AMOAE magnitude, suggesting that cochlear mechanics might play a role for AM perception. [Work supported by the Knowles Hearing Center and Northwestern University.]

Differential actions of isoflurane and ketamine-based anaesthetics on cochlear function in the mouse

Isoflurane is a volatile inhaled anaesthetic widely used in animal research, with particular utility for hearing research. Isoflurane has been shown to blunt hearing sensitivity compared with the awake state, but little is known about how isoflurane compares with other anaesthetics with regard to hair cell transduction and auditory neurotransmission. The current study was undertaken in C57Bl/6J and C129/SvEv strains of mice to determine whether isoflurane anaesthesia affects hearing function relative to ketamine-based anaesthesia. Cochlear function and central auditory transmission were assessed using auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE), comparing thresholds and input/output functions over time, for isoflurane vs. ketamine/xylazine/acepromazine anaesthesia. ABR thresholds at the most sensitive region of hearing (16 kHz) were initially higher under isoflurane anaesthesia. This reduced hearing sensitivity worsened over the 1 h study period, and also became evident with broadband click stimulus. Ketamine anaesthesia provided stable ABR thresholds. Although the growth functions were unchanged over time for both anaesthetics, the slopes under isoflurane anaesthesia were significantly less. Cubic (2f1–f2) DPOAE thresholds and growth functions were initially similar for both anaesthetics. After 60 min, DPOAE thresholds increased for both groups, but this effect was significantly greater with ketamine anaesthesia.The isoflurane-mediated increase in ABR thresholds over time is attributable to action on cochlear nerve activation, evident as a right-shift in the P1-N1 input/output function compared to K/X/A. The ketamine-based anaesthetic produced stable ABR thresholds and gain over time, despite a right-shift in the outer hair cell – mediated DPOAE input/output function.

Ear Canal Pressure Variations Versus Negative Middle Ear Pressure: Comparison Using Distortion Product Otoacoustic Emission Measurement in Humans

For more than a century, positive and/or negative ear canal air pressure (ECP) has often been employed to simulate negative middle ear pressure (MEP) in exploring the latter's effect on hearing sensitivity and outcomes of various physiological assessments of the auditory system. However, systematic investigation is lacking on validation of these practices. This study was aimed at comparing these air pressure variations in humans in terms of effect on distortion product otoacoustic emissions (DPOAEs) and discussing certain issues pertaining to the middle ear transfer function. The 2f1 - f2 DPOAE was measured for nine f2 frequencies from 600 to 8000 Hz in 27 adult ears under four air pressure conditions: normal MEP, negative MEP, and positive and negative ECPs. The subjects voluntarily induced negative MEPs with magnitudes ranging from -40 to -420 daPa, as estimated by the tympanometric peak pressure. For each negative MEP, positive and negative ECPs were applied, respectively, at the same magnitude in absolute value as the negative MEP after it was equalized. Negative MEP and ECP variations were compared in terms of change in DPOAE level. Positive ECP resembled negative MEP, showing a distinct frequency-specific model of effect on DPOAE level: (1) DPOAEs were attenuated the greatest for frequencies at and below 1000 Hz, which increased from 4-6 to 10-12 dB with increasing the pressure for the tested range; (2) DPOAE attenuation decreased with increasing frequency and was minimal at 2000 Hz; and (3) DPOAE level significantly declined for the frequencies between 2000 and 6000 Hz and tended to increase for high frequencies. Compared with a negative MEP, an equivalent negative ECP yielded a smaller reduction of DPOAE levels for frequencies below 2000 Hz, as well as 3000 Hz, but greater reduction for frequencies above 4000 Hz. One phenomenon that occurred under all three air pressures was a minimal change of the DPOAE level at 2000 Hz. This resulted in a peak at 2000 Hz in the DPOAE level change versus frequency function. Effects of negative MEP and ECP variations on DPOAEs in human ears are comparable, to a great extent, to findings from previous studies on hearing sensitivity in humans and tympanic membrane vibration at the umbo in human temporal bones. The present study demonstrates that positive ECP can be used to simulate negative MEP in research on the middle ear function in live humans. Results also suggest that long-lasting beliefs regarding the ECP effect on the middle ear conduction should be amended: (1) only positive ECP, not negative ECP, attenuates sound transmission more for low frequencies than for high frequencies, and (2) positive ECP has a greater effect than negative ECP only for low frequencies and not for high frequencies. Discussion of the present results together with those from previous studies sheds light on the middle ear dynamics under diverse pressure changes across the tympanic membrane and proposes that distorted configuration of the tympanic membrane and ossicular chain is the key factor in the effect of MEP or ECP on the middle ear sound transmission for low frequencies.

On the differential diagnosis of Ménière’s disease using low-frequency acoustic biasing of the 2f1–f2 DPOAE

We have cyclically suppressed the 2f1–f2 distortion product otoacoustic emission (DPOAE) with low-frequency tones (17–97 Hz) as a way of differentially diagnosing the endolymphatic hydrops assumed to be associated with Ménière’s syndrome. Round-window electrocochleography (ECochG) was performed in subjects with sensorineural hearing loss (SNHL) on the day of DPOAE testing, and from which the amplitude of the summating potential (SP) was measured, to support the diagnosis of Ménière’s syndrome based on symptoms. To summarize and compare the cyclic patterns of DPOAE modulation in these groups we have used the simplest model of DPOAE generation and modulation, by assuming that the DPOAEs were generated by a 1st-order Boltzmann nonlinearity so that the magnitude of the 2f1-f2 DPOAE resembled the 3rd derivative of the Boltzmann function. We have also assumed that the modulation of the DPOAEs by the low-frequency tones was simply due to a sinusoidal change in the operating point on the Boltzmann nonlinearity. We have found the cyclic DPOAE modulation to be different in subjects with Ménière’s syndrome ( n = 16) when compared to the patterns in normal subjects ( n = 16) and in other control subjects with non-Ménière’s SNHL and/or vestibular disorders ( n = 13). The DPOAEs of normal and non-Ménière’s ears were suppressed more during negative ear canal pressure than during positive ear canal pressure. By contrast, DPOAE modulation in Ménière’s ears with abnormal ECochG was greatest during positive ear canal pressures. This test may provide a tool for diagnosing Ménière’s in the early stages, and might be used to investigate the pathological mechanism underlying the hearing symptoms of this syndrome.

Effects of Negative Middle Ear Pressure on Distortion Product Otoacoustic Emissions and Application of a Compensation Procedure in Humans

This study was intended to systematically examine the effect of negative middle ear pressure (MEP) on distortion product otoacoustic emissions (DPOAEs) and to validate a compensation procedure to account for negative MEP encountered in DPOAE measurement. In experiment 1, the 2f1 - f2 DPOAE was measured for nine f2 frequencies from 600 to 8000 Hz in 16 adults under three MEP conditions: normal MEP, negative MEP, and compensated MEP. The subjects' voluntarily induced negative MEPs, with magnitudes ranging from -40 to -420 daPa, were measured tympanometrically with the tympanometric peak pressure. Each negative MEP was then compensated for by applying an equivalent amount of negative air pressure into the ear canal. The three MEP conditions were compared in terms of difference in DPOAE level. Experiment 2 was conducted to measure the DPOAE under normal and negative MEP conditions by using a different system with a higher frequency resolution in 19 subjects. Negative MEP generally attenuated DPOAEs more for low frequencies than for high frequencies. For the frequencies of 1000 Hz and below, the mean DPOAE level was reduced by at least 4 to 6 dB for negative MEPs lower than -100 daPa (i.e., less negative). Reduction of the DPOAE level increased with increasing negative MEP (e.g., 10 to 12 dB for -160 daPa and higher, i.e., more negative). For f2 = 2000, 4000, and 6000 Hz, the effect of negative MEP was not significant. For 3000 Hz, DPOAE-level reduction was significant (e.g., 5 dB for MEP = -70 to -95 daPa and up to 12 dB for -290 to -420 daPa). As a result, a peak at 2000 Hz and a notch at 3000 Hz appeared in the DPOAE change versus frequency function. For 8000 Hz, DPOAE levels tended to increase in high negative MEPs, although the changes were not significant. Intersubject variability in the effect of negative MEP on DPOAEs was large. As the negative MEPs were compensated for, the decreased DPOAE levels were significantly corrected. DPOAEs measured with higher resolution in experiment 2 verified the frequency-specific effects of negative MEPs. Results revealed that the peak and notch in the DPOAE change versus frequency function shifted toward higher frequencies when negative MEP was increased, and a second peak emerged at a higher frequency. Negative MEP substantially decreases DPOAE level for low frequencies and some mid-frequencies but tends to increase DPOAE level for high frequencies. Results suggest that any degree of negative MEP should be corrected to obtain an accurate outcome of DPOAE measurement. The MEP compensation procedure is effective in restoring normal DPOAEs in ears with negative MEPs. Examining changes in DPOAE level under negative MEP allows for further study of the transmission of acoustic signals through an altered middle ear system. A minimal change of DPOAE level at 2000 Hz indicates that the primary resonant frequency of the middle ear is lower than 2000 Hz. The variation in DPOAE change in the middle to high frequency range implies multiple resonances of the middle ear system.

Deafness and Stria Vascularis Defects in S1P2 Receptor-null Mice

The S1P(2) receptor is a member of a family of G protein-coupled receptors that bind the extracellular sphingolipid metabolite sphingosine 1-phosphate with high affinity. The receptor is widely expressed and linked to multiple G protein signaling pathways, but its physiological function has remained elusive. Here we have demonstrated that S1P(2) receptor expression is essential for proper functioning of the auditory and vestibular systems. Auditory brainstem response analysis revealed that S1P(2) receptor-null mice were deaf by one month of age. These null mice exhibited multiple inner ear pathologies. However, some of the earliest cellular lesions in the cochlea were found within the stria vascularis, a barrier epithelium containing the primary vasculature of the inner ear. Between 2 and 4 weeks after birth, the basal and marginal epithelial cell barriers and the capillary bed within the stria vascularis of the S1P(2) receptor-null mice showed markedly disturbed structures. JTE013, an S1P(2) receptor-specific antagonist, blocked the S1P-induced vasoconstriction of the spiral modiolar artery, which supplies blood directly to the stria vascularis and protects its capillary bed from high perfusion pressure. Vascular disturbance within the stria vascularis is a potential mechanism that leads to deafness in the S1P(2) receptor-null mice.

Contralateral suppression of distortion product otoacoustic emissions: Effect of the primary frequency in Dpgrams

The amplitude of the 2f1–f2 distortion product otoacoustic emission (DPOAE) can be suppressed by presenting contralateral acoustic stimulation. To test the hypothesis that DPOAE contralateral suppression is influenced by the primary frequency in DPgrams, DPgrams were recorded at resolutions of 1, 8, and 17 pts/octave, in the absence and presence of contralateral broadband noise (BBN). Participants were 20 normal-hearing human adults. In DPgrams with higher frequency resolutions, DPOAE suppression at amplitude peaks in DPgrams (8 pts/octave: Mean = − 0.92 dB, SD = 0.71 for BBN at 60 dB SPL; 17 pts/octave: Mean = − 0.25 to −1.44 dB, SD = 0.51 to 0.86 for BBN at 40 to 70 dB SPL, respectively) was larger than the suppression at the dips in DPgrams (8 pts/octave: Mean = − 0.13 dB, SD = 1.00; 17 pts/octave: Mean = − 0.03 to −0.73 dB, SD = 0.55 to 0.91). A larger intersubject variability in DPOAE contralateral suppression was observed at the dips. The results suggest that measuring DPOAE contralateral suppression at the primary frequencies corresponding to the peaks in DPgrams with higher frequency resolutions may improve the assessment of the efferent system function.

Influence of the sweeping direction of the primaries f1 and f2 in the assessment of distortion product otoacoustic emissions (DPOAEs) fine structure

It was studied if the sweeping direction of the primaries f1 and f2 influences fine structure measurements of the 2f1−f2 distortion product otoacoustic emission (DPOAE). Two different methodologies named DPOAE5ASC (ascending sweep) and DPOAE5DES (descending sweep) were implemented with the commercial system ILO96. Both methods perform fine structure measurements in the same frequency range (1.4–6 kHz) with L1/L2=65/45 dB, f2/f1=1.22 and 0.7 s averaging time per primary presented. DPOAE fine structures were measured in the right ear of 14 normal‐hearing subjects with both methods in a balanced experiment and without refitting the sound probe. Results showed that the two methods are highly repeatable and able to detect fine structures even in subjects with low S/N. However, when DPOAE5ASC measurements are compared with DPOAE5DES, fine structures appear shifted and the level contour is altered. A minor level difference was inadvertently induced due to differences in the level calibration procedure of the two...

Effect of aspirin on phase gradient of 2F1–F2 distortion product otoacoustic emissions

It is well known that aspirin consumption temporarily reduces overall otoacoustic emission (OAE) amplitude in humans. However, little is known about changes in the separate components of distortion product otoacoustic emissions (DPOAE), which may be distinguished by examining phase gradients. The effects of aspirin on the phase gradient of the DPOAE 2F1–F2 obtained with fixed frequency ratio sweeps were studied longitudinally in a group of twelve subjects in whom a temporary hearing loss was induced by aspirin consumption. DPOAE were recorded daily for two days pre-aspirin consumption, during the three days of aspirin consumption and two days afterwards. DP-grams were recorded over a restricted frequency range centered on 2, 3, 4 and 6 kHz with the following stimulus levels: L1/L2 of 60/50–80/70 in 10-dB steps. The effects of aspirin on the phase gradients varied between the subjects and across frequency: the general trend was that the phase gradient became steeper across successive sessions for the higher frequencies, while no significant effect was found at the lower frequencies. These results suggest that aspirin may have more persistent effects on cochlear function than are disclosed by measurements of hearing threshold level or DPOAE amplitude. Particularly, DPOAE phase gradient appears to be increased by aspirin consumption and has not recovered two days after cessation of aspirin intake, despite almost complete recovery of DPOAE amplitude and hearing threshold levels. These findings may suggest differential effects on the distortion and reflection mechanisms considered to underlie DPOAE generation.

Effects of glucocorticoid receptor antagonist on CAPs threshold shift due to short-term sound exposure in guinea pigs

Objective: The steroid drugs are used for the standard treatment of sudden sensorineural hearing loss. However, clinical results on the effect of glucocorticoids in acoustic trauma have not yet been understood well. The effects of glucocorticoid receptor (GR) antagonist, mifepristone, on the cochlea sensitivity loss due to short-term sound exposure were studied in the guinea pig. Methods: Mifepristone (20 mg/kg) was injected subcutaneously immediately after the noise exposure to 4 kHz pure tone of 100 or 120 dB SPL for 10 min and also at 1 day and 3 days later. Seven days after the sound exposure, the compound action potentials (CAPs) of the cochlear nerve and the 2f1–f2 distortion product oto-acoustic emissions (DPOAEs) were recorded. Results: No significant CAP threshold losses were observed in either mifepristone or saline administration after the exposure at 100 dB SPL. After the exposure at 120 dB SPL, administration of mifepristone elevated the CAP threshold at 5–8 kHz significantly as compared with the saline administration. The DPOAE output shifts of both saline and mifepristone groups were similar to each other. Conclusion: Mifepristone may influence inner hair cells (IHCs) and afferent nerve fibers beneath the IHC without having influence on outer hair cells (OHCs). It is suggested that glucocorticoid plays an important role in the improvement of hearing impairment after loud sound exposure.

Effect of acute inner ear pressure changes on low-level distortion product otoacoustic emissions in the guinea pig

Objective—To determine a relation between acute inner ear pressure changes and cochlear function as measured by low-level 2f1–f2 distortion product otoacoustic emissions (DPOAEs).Material and Methods—During and after a change in inner ear pressure induced by injection or aspiration of perilymph, the 2f1–f2 DPOAE at 4.5 kHz generated by low-level primaries was recorded in the guinea pig.Results—Large changes in overall inner ear pressure produced only small changes in the 2f1–f2 amplitude and phase. During injection of 0.5 μl of artificial perilymph into the scala tympani over a 10-s period, the mean inner ear pressure increased by ≈500 Pa, with an accompanying mean increase in the 2f1–f2 amplitude of 0.7 dB. During aspiration of 0.5 μl of perilymph over a 10-s period, the mean inner ear pressure decreased by ≈700 Pa, with an accompanying mean decrease in the 2f1–f2 amplitude of 0.9 dB. Changes in DPOAE amplitude followed inner ear pressure changes with a delay of 1–2 s. The magnitude and sign of the amplitude changes can (partly) be explained by a change in oval window stiffness. No explanation was found for the measured delay.Conclusion—Clinically, these experiments can be of value in gaining insight into the pathophysiological mechanisms of pathological pressure changes as seen in Ménière's disease and perilymphatic fistulae.

Distortion product otoacoustic emissions provide clues to hearing mechanisms in the frog

Cubic distortion product otoacoustic emissions (DPOAEs) were recorded from 10 Rana pipiens and 10 Rana catesbeiana, 5 males and 5 females each. The I/O curves obtained from the amphibian papilla (AP) of both species are very similar to the respective mammalian curves, indicating that, like in the mammalian cochlea, there may be an amplification process active in the frog AP. The DPOAE level dependence on primary levels is also similar to the mammalian case, suggesting a mechanical structure in the frog inner ear may be functioning analogously to the mammalian basilar membrane. DPOAE audiograms were obtained for primary frequencies spanning the animals hearing range and levels determined by the previous experiments. R. catesbeiana produce stronger emissions than R. pipiens and, consistent with previously reported sexual dimorphism in the mammalian and anuran auditory systems, females from both species produce stronger emissions than males. Additionally, the 2f1−f2 DPOAE is generated primarily at the DPOAE frequency place, while the 2f2−f1 DPOAE is generated primarily at a frequency place between the primaries. This difference in mammalian and frog DPOAEs may be linked to an anatomical difference that results in the acoustic energy following opposite paths through the mammalian and frog inner ears. [Work supported by NIH Grant No. DC-00222 to Peter M. Narins.] a)Currently at De Paul Univ., School of Music, Chicago, IL 60614.

Rapid adaptation of the 2 f1– f2 DPOAE in humans: Binaural and contralateral stimulation effects

The present data were collected in humans to characterize the effects of monaural and binaural stimulation and contralateral noise on the 2 f 1– f 2 distortion-product otoacoustic emission (DPOAE) adaptation response. DPOAE levels ( f 2/ f 1=1.21, L 1=70 dB SPL, L 2=65 dB SPL) were measured in both ears for a range of f 2 frequencies (1.2 to 10.0 kHz). The f 2 frequency producing the largest amplitude DPOAE was used for further testing employing three different stimulus conditions: the primary tones were presented to only one ear for 4 s; the two tones were presented simultaneously in both ears; and, contralateral broadband noise (60 dB SPL) was presented for 5 s, beginning 4 s after the onset of the monaural primaries in the test ear. Acoustic reflex thresholds were measured to verify that the middle-ear muscles played no systematic role in the measured DPOAE reductions. Estimates of monaural rapid adaptation levels and time constants agreed well with previous human findings. The magnitude of the rapid adaptation under binaural stimulation, as compared with monaural primaries, was 25% greater on average, though adaptation time constants were comparable. With added contralateral noise, the average DPOAE suppression was 1.1 dB (0.3–2.7 dB). The magnitude of the monaural adaptation and the effects of binaural and contralateral stimulation, however, were smaller than those measured previously in experimental animals, though the time constants were in good agreement.

Weighted DPOAE Input/Output-functions: A tool for automatic assessment of hearing loss in clinical application

2f1 – f2 distortion product otoacoustic emission (DPOAE) input/output functions were recorded in 796 ears with sensorineural hearing loss at up to 50 frequencies between 500 Hz and 8 kHz in a wide level range from L2 = 20 to L2 = 65 dB SPL at up to 10 levels (“scissor paradigm”, L1 = 0.4L2 + 39, f2/f1 = 1.2). DPOAEs were accepted as valid for signal-to-noise ratios (SNR) only if they exceeded 6 dB. To assess the DPOAE threshold, DPOAE input/output functions (L2 – DPOAE sound pressure diagram) were subject to linear regression and extrapolation; the point of intersection with the L2 coordinate was then interpreted as DPOAE threshold [1]. The linear fit of the function pDP (L2) = a + bL2 (whereby a and b represent the threshold and the slope of the DPOAE growth, respectively), reflects compression and sensitivity of the cochlear amplifier. Using a weighted least mean square error (LMSE) regression, more than 70 % of the DPOAE I/O functions of the data set can be used for the threshold estimation. High correlation and relatively small differences between objectively estimated DPOAE threshold and subjectively determined hearing threshold of pure-tone audiograms prove that the weighted extrapolation of DPOAE I/O functions can be a valuable clinical tool for the objective assessment of cochlear hearing loss.