2f1-f2 Distortion Product Otoacoustic Emissions Research Articles

Similar Tuning of Distortion-Product Otoacoustic Emission Ratio Functions and Cochlear Vibrations in Mice.

When elicited by two stimulus tones (at frequencies f1 and f2, f2 > f1), the amplitudes of specific distortion-product otoacoustic emission (DPOAE) components exhibit a characteristic bandpass shape as the ratio between f2 and f1 is varied. This bandpass shape has been attributed to various mechanisms including intracochlear resonance, suppression, and wave interference, and has been proposed to be related to cochlear frequency tuning. While human studies suggest modest correlations between psychophysical tuning and the tuning of DPOAE amplitude vs. f2/f1 ratio functions, a relationship between the latter and the tuning of cochlear mechanical responses has yet to be established. This was addressed here through direct comparisons of DPOAEs and cochlear vibrations in wild-type CBA/CaJ mice. DPOAEs were elicited using a fixed-f2, swept-f1 paradigm, and optical coherence tomography was used to measure displacements from cochlear locations with characteristic frequencies near f2. The tuning sharpness of 2f1-f2 DPOAE ratio functions was found to be remarkably similar to that of basilar membrane and/or tectorial membrane responses to single tones, with the tuning sharpness of all responses increasing similarly with decreasing stimulus level. This relationship was observed for f2 frequencies ranging from ~8 to 22 kHz. Intracochlear distortion products did not exhibit a bandpass shape as the f2/f1 ratio was varied, indicating that interference between distortion products traveling to the stapes may be responsible for the tuning of the DPOAE ratio function. While these findings suggest that DPOAE ratio functions could be used to noninvasively infer cochlear tuning, it remains to be determined whether this relationship holds in other species and for lower frequency regions.

Optimizing distortion product otoacoustic emission recordings in normal-hearing ears by adopting cochlear place-specific stimuli.

Distortion product otoacoustic emissions (DPOAEs) provide a window into active cochlear processes and have become a popular clinical and research tool. DPOAEs are commonly recorded using stimulus with fixed presentation levels and frequency ratio irrespective of the test frequency. However, this is inconsistent with the changing mechanical properties of the cochlear partition from the base to the apex that lend specific frequency-dependent spatial properties to the cochlear traveling wave. Therefore, the frequency and level characteristics between the stimulus tones should also need to be adjusted as a function of frequency to maintain optimal interaction between them. The goal of this investigation was to establish a frequency-specific measurement protocol guided by local cochlear mechanics. A broad stimulus parameter space extending up to 20 kHz was explored in a group of normal-hearing individuals. The stimulus frequency ratio yielding the largest 2f1-f2 DPOAE level changed as a function of frequency and stimulus level. Specifically, for a constant stimulus level, the frequency ratio producing the largest DPOAE level decreased with increasing frequency. Similarly, at a given f2 frequency, the stimulus frequency ratio producing the largest DPOAE level became wider as stimulus level increased. These results confirm and strengthen our current understanding of DPOAE generation in the normally functioning cochlea and expand our understanding to previously unexamined higher frequencies. These data support the use of frequency- and level-specific stimulus frequency ratios to maximize DPOAE generation.

Characterizing the Relationship Between Reflection and Distortion Otoacoustic Emissions in Normal-Hearing Adults.

Otoacoustic emissions (OAEs) arise from one (or a combination) of two basic generation mechanisms in the cochlea: nonlinear distortion and linear reflection. As a result of having distinct generation processes, these two classes of emissions may provide non-redundant information about hair-cell integrity and show distinct sensitivities to cochlear pathology. Here, we characterize the relationship between reflection and distortion emissions in normal hearers across a broad frequency and stimulus-level space using novel analysis techniques. Furthermore, we illustrate the promise of this approach in a small group of individuals with mild-moderate hearing loss. A "joint-OAE profile" was created by measuring interleaved swept-tone stimulus-frequency OAEs (SFOAEs) and 2f1-f2 distortion-product OAEs (DPOAEs) in the same ears using well-considered parameters. OAE spectra and input/output functions were calculated across five octaves. Using our specific recording protocol and analysis scheme, SFOAEs in normal hearers had higher levels than did DPOAEs, with the most pronounced differences occurring at the highest stimulus levels. Also, SFOAE compression occurred at higher stimulus levels (than did DPOAE compression) and its growth in the compressed region was steeper. The diagnostic implications of these findings and the influence of the measurement protocol on both OAEs (and on their relationship) are discussed.

Weakened Cochlear Nonlinearity During Human Aging and Perceptual Correlates.

As humans age, compressive nonlinearity-a hallmark of healthy cochlear function-changes. The nonlinear distortion-component of the distortion product otoacoustic emission (DPOAE) provides a noninvasive gauge of cochlear nonlinearity. Earlier published work has suggested that weakened nonlinearity begins in middle age; the current work extends this investigation into the eight decade of life using advanced DPOAE data collection and analysis methods as well as multiple metrics of nonlinearity, including a test of loudness scaling. The 2f1-f2 DPOAE was recorded in 20 young adults, 25 middle-aged adults and 32 older adults from f2 = 0.78 to 9.4 kHz with primary tones (f2/f1 = 1.22) swept upward at a rate of 0.5 octave/sec. Only frequencies with audiometric thresholds ≤20 dB HL were included in the analysis and to the extent possible, ears were audiometrically matched to eliminate hearing threshold as a contributing factor to the observed age effects. Input/output functions were generated for the separated distortion-component of the DPOAE to probe compressive nonlinearity of the cochlea, and ipsilateral suppression of the DPOAE was conducted to probe two-tone suppression. To investigate the perceptual effects of weakening nonlinearity on loudness perception, the same subjects performed categorical loudness scaling. Age effects on both DPOAE and loudness scaling variables were assessed, and correlations were conducted between key OAE and perceptual metrics. Age × Frequency ANOVAs revealed that the compression knee of the DPOAE I/O function occurred at higher stimulus levels in both groups of older adults compared to young adults, suggesting an expanded linear range with aging; also, the compressive slope (growth beyond the knee point) was steeper in older-adults compared to young adults. These results were most notable at high frequencies. ANOVAs including age and auditory threshold as factors confirmed that the age effect observed was independent of threshold. Additionally, in smaller subsets of subjects with audiometrically matched data, these same trends persisted, further ruling out hearing threshold as an influential factor. The growth of DPOAE ipsilateral suppression was shallower near 4 kHz in middle-aged and older adults compared to young adults and elevated suppression thresholds were observed. Results of categorical loudness scaling showed steeper growth of loudness for older adults and, at fixed sensation levels (dB SL), the older-adult group rated tones as louder than did their young-adult counterparts, suggesting abnormal loudness growth and perception. Several correlations between the compression knee of the DPOAE I/O function and key metrics of loudness scaling were significant and accounted for up to one-third of the variance. Results indicate that the aging cochlea begins to show weakened nonlinearity in middle age and it progressively weakens further into senescence. The perceptual impact of weakened nonlinearity during aging is manifested as abnormal loudness judgments; that is, in older-adult ears, a tone considered comfortable or medium in young-adult ears can be considered loud. The biophysical origin of this weakened nonlinearity is not known. It is hypothesized to reflect aging-related damage to, or loss of, outer hair cells and their stereocilia. More work is warranted to better define the perceptual impact of a linearized cochlear response in older adults and to consider how this deficit might impact the fitting of hearing aids and other intervention strategies.

An intracochlear DP-gram: Proof of principle in noise-damaged rabbits

Distortion-product otoacoustic emissions (DPOAEs) can be used to assess cochlear damage and are often evaluated by generating a DP-gram in which 2f1-f2 DPOAE levels are plotted as a function of the higher-frequency primary at f2. DPOAEs are derived from the reverse propagation of distortion-product (DP) wavelets from their intracochlear sites of generation to emerge as measurable acoustic signals in the outer ear canal. However, at least, some of these same wavelets also propagate within the cochlea in the normal forward direction to the DP-frequency (fdp) place, where they appear as intracochlear distortion products (iDPs). Depending on several factors, especially, the extent to which DP wavelets add or cancel with each other in phase, one might expect iDPs to differ from DPOAEs in their ability to map the frequency pattern of cochlear damage. In the present study, the behavior of 2f1-f2 iDPs was inferred by interacting a probe tone (f3) with the iDP of interest to produce a ‘secondary’ DPOAE (i.e., DPOAE2ry), which was then used to infer the level of 2f1-f2 iDPs as a function of the f2-test frequency, thus, constituting a newly developed iDP-gram. To determine the feasibility of and potential applications for the iDP-gram procedure, noise-induced cochlear damage was assessed in two ‘test’ rabbits, one of which exhibited a well-defined punctate loss in their DP-gram, while the other exhibited a broader V-shaped loss. To validate the iDP-gram procedure, standard DP-grams were simultaneously collected and compared to their iDP-gram counterparts. Cochlear damage was independently assessed using auditory brainstem responses (ABRs) describing threshold-shift patterns to which both DP-gram types could be compared. Each DP-gram variety, to some extent, was able to detect a punctate loss in one rabbit and a broader V-shaped loss in the other. For the punctate-loss subject, the standard DP-gram showed a more generalized loss across test frequencies, while iDP-grams showed several localized notches superimposed on the generalized-loss pattern. In general, for the V-shaped loss pattern, both DP-gram types performed very well at detecting the large loss, with the lower primary-tone levels being most sensitive. At the narrow primary-tone ratios of f2/f1=1.05, standard DP-grams were unable to detect either loss pattern, while for the punctate loss, they paradoxically showed enhancement. Notably, the simultaneously collected iDP-grams performed favorably at the narrow-ratio setting, which is consistent with the notion that DPs travelling toward the 2f1-f2 fdp place are not subject to the cancellation of wavelets typical for narrow primary-ratio conditions that can confound measures of DPs moving towards the ear canal to emerge as DPOAEs.

Onset kinetics of noise-induced purinergic adaptation of the 'cochlear amplifier'.

A major component of slowly reversible hearing loss which develops with sustained exposure to noise has been attributed to release of ATP in the cochlea activating P2X2 receptor (P2X2R) type ATP-gated ion channels. This purinergic humoral adaptation is thought to enable the highly sensitive hearing organ to maintain function with loud sound, protecting the ear from acoustic overstimulation. In the study that established this hearing adaptation mechanism as reported by Housley et al. (Proc Natl Acad Sci U S A 110:7494-7499, 2013), the activation kinetics were determined in mice from auditory brainstem response (ABR) threshold shifts with sustained noise presentation at time points beyond 10min. The present study was designed to achieve finer resolution of the onset kinetics of purinergic hearing adaptation, and included the use of cubic (2f1-f2) distortion product otoacoustic emissions (DPOAEs) to probe whether the active mechanical outer hair cell 'cochlear amplifier' contributed to this process. We show that the ABR and DPOAE threshold shifts were largely complete within the first 7.5min of moderate broadband noise (85dB SPL) in wildtype C57Bl/6J mice. The ABR and DPOAE adaptation rates were both best fitted by a single exponential function with ~ 3min time constants. ABR and DPOAE threshold shifts with this noise were minimal in mice null for the P2rx2 gene encoding the P2X2R. The findings demonstrate a considerably faster purinergic hearing adaptation to noise than previously appreciated. Moreover, they strongly implicate the outer hair cell as the site of action, as the DPOAEs stem from active cochlear electromotility.

The influence of distributed source regions in the formation of the nonlinear distortion component of cubic distortion-product otoacoustic emissions.

Distortion product otoacoustic emissions (DPOAEs) are evoked by two stimulus tones with frequency f1 and f2 of ratio f2/f1 in the range between approximately 1.05 and 1.4. This study theoretically and experimentally analyzes the cubic 2f1-f2 DPOAE for different stimulus levels of one of the tones while the other is constant. Simulations for f2/f1 of 1.2 and moderate stimulus levels (30-70 dB sound pressure level) indicate that cubic distortion products are generated along a relatively large length of the basilar membrane, the extent of which increases with stimulus level. However, apical from the place of maximum nonlinear force, the wavelets generated by these distributed sources mutually cancel. Therefore, although the spatial extent of the primary DPOAE sources broadens with increasing stimulus level (up to 1.5 oct), the basilar-membrane region contributing to the DPOAE signal is relatively narrow (0.6 oct) and level independent. The observed dependence of DPOAE amplitude on stimulus level can be well-approximated by a point source at the basilar-membrane place where the largest distortion product (maximum of the nonlinear force) is generated. Onset and offset of the DPOAE signal may contain amplitude overshoots (complexities), which are in most cases asymmetrical. Two-tone suppression was identified as the main cause of these onset and offset complexities. DPOAE measurements in two normal-hearing subjects support the level dependence of the steady-state DPOAE amplitude and the asymmetry in the onset and offset responses predicted by the theoretical analysis.

Abnormal fast fluctuations of electrocochleography and otoacoustic emissions in Menière's disease

The responses of cochlear hair cells to sound stimuli depend on the resting position of their stereocilia bundles, which is sensitive to the chemical and mechanical environment. Cochlear hydrops, a hallmark of Menière's disease (MD), which is likely to come with disruption of this environment, results in hearing symptoms and electrophysiological signs, such as excessive changes in the cochlear summating potential (SP) and in the postural shifts of distortion-product otoacoustic emissions (DPOAEs). Here, SP from the basal part of the cochlea and DPOAEs from the apical part of the cochlea were recorded concomitantly in 73 patients with a definite MD, near an attack (n = 40) or between attacks with no clinical symptoms (n = 33), to compare their sensitivities to posture and evaluate their stability. The phase of the 2f1-f2 DPOAEs was monitored during body tilt, with stimuli f1 = 1 kHz and f2 = 1.2 kHz at 72 dB SPL. Extratympanic electrocochleography was performed in response to 95-dBnHL clicks. The normal limits of the DPOAE phase shift with body tilt, [−18°, +38°], and of the SP to action-potential (AP) ratio, <0.40, were exceeded in 75% and 60% of patients, respectively, near an attack. In these patients, but not in the asymptomatic ones, both tests reveal fluctuating cochlear responses from one data sample to the next. They emphasize how hydrops hinders normal hair-cell operation and may generate fast fluctuations in inner-ear functioning. If these fluctuations also occur on shorter time scales, it might explain the imperfect diagnostic sensitivity of SP and DPOAE tests, as averaging procedures would tend to level out transient fluctuations characteristic of hydrops.

Distortion-product otoacoustic emission fine structure as an indicator of combination-tone-mediated masking release

During simultaneous masking, when the probe (fp) is higher in frequency than the masker (fm), the cubic difference tone (CDT; fcdt = 2fm-fp) can provide masking release. Given their shared origin, the 2f1-f2 distortion-product otoacoustic emission (DPOAE) may be a physiological correlate of CDT-mediated masking release [McFadden et al. (2012). J. Acoust. Soc. Am. 132, 968–983]. To test this hypothesis, masking release and DPOAEs were measured in normal-hearing listeners for 2 and 4 kHz probes. Probe threshold was measured in the presence of a masker (fp/fm = 1.2) and masker-suppressor pair. The suppressor was designed to mask detection of the CDT. Masking release was calculated as the change in masked-probe threshold resulting from presentation of the suppressor. DPOAEs were measured for an f2 (f2/f1 = 1.2) between 1.8 and 2 kHz (6-Hz intervals) and between 3.6 and 4.4 kHz (12-Hz intervals). Masking release was associated with DPOAE fine structure. Listeners without masking release lacked DPOAE fine struc...

Adaptation of distortion product otoacoustic emissions predicts susceptibility to acoustic over-exposure in alert rabbits.

A noninvasive test was developed in rabbits based on fast adaptation measures for 2f1-f2 distortion-product otoacoustic emissions (DPOAEs). The goal was to evaluate the effective reflex activation, i.e., "functional strength," of both the descending medial olivocochlear efferent reflex (MOC-R) and the middle-ear muscle reflex (MEM-R) through sound activation. Classically, it is assumed that both reflexes contribute toward protecting the inner ear from cochlear damage caused by noise exposure. The DP-gram method described here evaluated the MOC-R effect on DPOAE levels over a two-octave (oct) frequency range. To estimate the related activation of the middle-ear muscles (MEMs), the MEM-R was measured by monitoring the level of the f1-primary tone throughout its duration. Following baseline measures, rabbits were subjected to noise over-exposure. A main finding was that the measured adaptive activity was highly variable between rabbits but less so between the ears of the same animal. Also, together, the MOC-R and MEM-R tests showed that, on average, DPOAE adaptation consisted of a combined contribution from both systems. Despite this shared involvement, the amount of DPOAE adaptation measured for a particular animal's ear predicted that ear's subsequent susceptibility to the noise over-exposure for alert but not for deeply anesthetized rabbits.

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.

Time-domain demonstration of distributed distortion-product otoacoustic emission components

Distortion-product otoacoustic emissions (DPOAEs) were measured in rabbits as time waveforms by employing a phase-rotation technique to cancel all components in the final average, except the 2f1-f2 DPOAE. Subsequent filtering allowed the DPOAE waveform to be clearly visualized in the time domain. In most conditions, f2 was turned off for 6 ms, which produced a gap so that the DPOAE was no longer generated. These procedures allowed the DPOAE onset as well as the decay during the gap to be observed in the time domain. DPOAEs were collected with L1 = L2 = 65-dB sound pressure level primary-tone levels for f2/f1 ratios from 1.25 to 1.01 in 0.02 steps. Findings included the appearance of complex onsets and decays for the DPOAE time waveforms as the f2/f1 ratio was decreased and the DPOAE level was reduced. These complexities were unaffected by interference tones (ITs) near the DPOAE frequency place (fdp), but could be removed by ITs presented above f2, which also increased DPOAE levels. Similar outcomes were observed when DPOAEs were measured at a sharp notch in the DPOAE level as a function of the f2 primary tone frequency, i.e., DP-gram. Both findings were consistent with the hypothesis that the DPOAE-ratio function, and some notches in the DP-gram, are caused by interactions of distributed DPOAE components with unique phases.

Investigating the wave-fixed and place-fixed origins of the 2f1-f2distortion product otoacoustic emission within a micromechanical cochlear model

The 2f(1)-f(2) distortion product otoacoustic emission (DPOAE) arises within the cochlea due to the nonlinear interaction of two stimulus tones (f(1) and f(2)). It is thought to comprise contributions from a wave-fixed source and a place-fixed source. The generation and transmission of the 2f(1)-f(2) DPOAE is investigated here using quasilinear solutions to an elemental model of the human cochlea with nonlinear micromechanics. The micromechanical parameters and nonlinearity are formulated to match the measured response of the cochlea to single- and two-tone stimulation. The controlled introduction of roughness into the active micromechanics of the model allows the wave- and place-fixed contributions to the DPOAE to be studied separately. It is also possible to manipulate the types of nonlinear suppression that occur within the quasilinear model to investigate the influence of stimulus parameters on DPOAE generation. The model predicts and explains a variety of 2f(1)-f(2) DPOAE phenomena: The dependence of emission amplitude on stimulus parameters, the weakness of experiments designed to quantify cochlear amplifier gain, and the predominant mechanism which gives rise to DPOAE fine structure. In addition, the model is used to investigate the properties of the wave-fixed source and how these properties are influenced by the stimulus parameters.

Genome-wide linkage analyses identify Hfhl1 and Hfhl3 with frequency-specific effects on the hearing spectrum of NIH Swiss mice

BackgroundThe mammalian cochlea receives and analyzes sound at specific places along the cochlea coil, commonly referred to as the tonotopic map. Although much is known about the cell-level molecular defects responsible for severe hearing loss, the genetics responsible for less severe and frequency-specific hearing loss remains unclear. We recently identified quantitative trait loci (QTLs) Hfhl1 and Hfhl2 that affect high-frequency hearing loss in NIH Swiss mice. Here we used 2f1-f2 distortion product otoacoustic emissions (DPOAE) measurements to refine the hearing loss phenotype. We crossed the high frequency hearing loss (HFHL) line of NIH Swiss mice to three different inbred strains and performed linkage analysis on the DPOAE data obtained from the second-generation populations.ResultsWe identified a QTL of moderate effect on chromosome 7 that affected 2f1-f2 emissions intensities (Hfhl1), confirming the results of our previous study that used auditory brainstem response (ABR) thresholds to identify QTLs affecting HFHL. We also identified a novel significant QTL on chromosome 9 (Hfhl3) with moderate effects on 2f1-f2 emissions intensities. By partitioning the DPOAE data into frequency subsets, we determined that Hfhl1 and Hfhl3 affect hearing primarily at frequencies above 24 kHz and 35 kHz, respectively. Furthermore, we uncovered additional QTLs with small effects on isolated portions of the DPOAE spectrum.ConclusionsThis study identifies QTLs with effects that are isolated to limited portions of the frequency map. Our results support the hypothesis that frequency-specific hearing loss results from variation in gene activity along the cochlear partition and suggest a strategy for creating a map of cochlear genes that influence differences in hearing sensitivity and/or vulnerability in restricted portions of the cochlea.

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.

Parameters to Maximize 2f2-f1 Distortion Product Otoacoustic Emission Levels

Past research has established parameters for the 2f1-f2 distortion product otoacoustic emissions (DPOAEs) that enhance response levels (e.g., L1 - L2 = 10 dB; f2/f1 = 1.22; L1, L2 = 65, 55 dB SPL). These same parameters do not optimize 2f2-f1 DPOAEs. Therefore, this study was conducted to evaluate more completely those parameters that produce the most robust 2f2-f1 output. Input-output functions of the 2f2-f1 component were obtained from 20 normal-hearing adults (with f2 = 2000 Hz and 4000 Hz). Frequency ratios, level differences, and overall sound levels were manipulated with parameter combinations chosen to expand on information established in previous studies. The DPOAE signal-to-noise ratio (SNR), response presence, and output levels were measured. In general, mean SNRs and 2f2-f1 levels were greater, and DPOAEs were present more often for 2000 than for 4000 Hz across all parameter combinations. No single parameter combination resulted in pronounced maxima for 2f2-f1, which is consistent with past studies but is in sharp contrast to results for the more familiar 2f1-f2. Overall, the results suggest that to maximize the 2f2-f1 level, lower test frequencies, low frequency ratio, essentially equal levels of primary tones, and moderate stimulus levels are best, and such parameters might be important for applying DPOAE measurement to assessment of normal and impaired auditory function.

Changes in distortion product otoacoustic emission (DPOAE) fine structure due to contralateral acoustic stimulation

Contralateral acoustic stimulation (CAS) can cause changes in the amplitude of the 2f1-f2 DPOAE in humans - most probably mediated by the medial olivocochlear reflex. DPOAE amplitude changes due to CAS show large interindividual variability and large changes from suppression to enhancement for small changes of the primary levels. The underlying mechanisms of these effects are still not fully understood. We hypothesize that the two interacting DPOAE sources might be differently affected by the CAS. If so, CAS will cause specific changes in DPOAE fine structure. Therefore, DPOAE fine structures were measured using frequency-modulated primaries (f2: 1500-3000 Hz, f2/f1: 1.2; L2: 60 dB SPL; L1: 58, 63, 68 dB SPL) without and with a broadband CAS (50 dB SPL). The fine structure changes and shifts according to CAS were analyzed in detail - including latency windowing to separate the contributions from the two interacting DPOAE sources. The results indicate, e.g., that there is no “true” enhancement in terms of enhanced cochlear activity during broadband CAS. Rather there are slight frequency shifts in DPOAE fine structure due to changes in the relative contribution of the two DPOAE sources. This shift can lead to observations of “pseudo” enhancement of up to 20 dB for isolated frequencies.

Contralateral noise has possible asymmetric frequency-sensitive effect on the 2F1-F2 otoacoustic emission in humans

Contralateral acoustic stimulation has been shown to produce a suppressive effect on the 2F1-F2 distortion-product otoacoustic emission (DPOAE). According to reports by other studies, there is a frequency-specific suppressive region between 1 and 2kHz when the contralateral broadband or narrowband noise stimulation contains energy close to or near the F2 frequencies in that region. In general the broader the bandwidth of the noise stimulation, the greater is the suppressive effect. A frequency-sensitive region between 1 and 2kHz has also been suggested as narrowband noises with center frequencies remote from the F2 frequency seems to produce suppression in the same defined region. In order to test this hypothesis, narrowband noises wide enough to elicit suppression with center frequencies unmatched to the F2 frequencies were employed in the present study. For the right ear, a strong frequency-sensitive suppressive region was noted for the F2 frequency at 2kHz, but not at 1 and 4kHz. The left ear had some suppression at 1kHz, but this effect was not as robust as seen in the right ear. The apparent suppressive differences between ears suggest a possible MOC reflex asymmetry that has not previously been described for DPOAEs. These results suggest that physiological differences between ears and possibly handedness must be taken into account when examining contralateral suppression to narrowband noises. Furthermore, the frequency contributions of the contralateral stimulus may have a greater complex interaction with the cochlear physiology than previously considered.

Neurotoxicity of BFM-95 on the Medial Olivocochlear Bundle Assessed by Means of Contralateral Suppression of 2f1-f2 Distortion Product Otoacoustic Emissions

Berlin-Frankfurt-Munster 95 (BFM-95) is a common chemotherapeutic protocol against acute lymphoblastic leukemia (ALL). This prospective study investigates whether this protocol has an adverse effect on the medial olivocochlear bundle (MOCB) and/or outer hair cells' (OHCs) function. The distortion product otoacoustic emissions (DPOAEs) and their suppression by means of contralateral application of white noise were used for assessing the function of OHCs and the MOCB, respectively. Prospective study. Oncology and otorhinolaryngology departments in a pediatric hospital. Thirty-six children treated with ALL-BFM-95. Before chemotherapy, a baseline audiologic evaluation with tympanogram, standard and extended high frequency, pure-tone audiometry, and DPOAEs in the absence and presence of white noise was performed in all children. This population was divided in three groups. In a first group (n = 12), the evaluation was repeated after four sessions of vincristine administration; in the second group (n = 12), after 8 sessions; and in the third group (n = 12), several months after completion of the protocol. DPOAEs suppression by contralateral application of white noise. In the first and the third groups, we observed no changes in DPOAE amplitudes. Nevertheless, in the second group, the DPOAEs demonstrated significant decrease at 1416, 1685, 2002, and 2380 Hz. At baseline examination, all groups presented significant suppression at all frequencies. After eight vincristine sessions, instead of suppression, an increase of amplitudes was noted at 5 of 12 frequencies. Efferent-mediated DPOAE suppression reappeared in the third group at all frequencies (significant at 5 of 12 frequencies). ALL-BFM-95 seems to exert an early and reversible toxic effect on the MOCB, whereas its effects on OHCs are minimal and reversible. These minimal cochleotoxic and neurotoxic properties of ALL-BFM-95 might prove useful for research studies on the role of efferent innervation in hearing.

Distortion product otoacoustic emission of symphony orchestra musicians before and after rehearsal

The 2f1-f2 distortion product otoacoustic emission (DPOAE) and hearing levels are obtained for 12 normal-hearing symphony orchestra musicians both before and after their rehearsal. The DPOAE fine structures are determined and analyzed according to the character and prevalence of ripples. Hearing levels, DPOAE levels, and DPOAE fine structures before and after rehearsal are similar, indicating that no or marginal temporary change of the state of hearing were caused by the exposure. The data were further compared to similar data for occupationally nonexposed subjects, one group which was age and gender matched, and other two groups of younger individuals (one group with better hearing levels than the other). The data for the age and gender matched group compared well with the musicians data (and the data for the group of better-hearing younger individuals). In general, the analyses of hearing thresholds and DPOAE data thus lead to the same conclusions concerning the state of hearing.