Barden B. Stagner

Acoustic distortion products in humans: Systematic changes in amplitude as a function of f2/f1 ratio

The effects of primary-tone separation on the amplitude of distortion-product emissions (DPEs) at the 2f1-f2 frequency were systematically examined in ten ears of five subjects. All individuals had normal hearing and middle-ear function based upon standard clinical measures. Acoustic-distortion products were elicited at 1, 2.5, and 4 kHz by equilevel primaries at 65, 75, and 85 dB SPL, while f2/f1 ratios were varied in 0.02 increments from 1.01-1.41 (4 kHz), 1.01-1.59 (2.5 kHz), or 1.01-1.79 (1 kHz). A principal outcome reflected in the detailed structure of both average and individual ratio functions was a nonmonotonic change in DPE amplitude as the ratio of f2/f1 increased. Despite the presence of amplitude nonmonotonicities, there was clearly a region of f1 and f2 separation that generated a maximum DPE. The effects of primary-tone separation on DPE amplitudes were systematically related to DPE frequency and primary-tone level. For all three levels of stimulation, the f2/f1 ratio was inversely related to DPE frequency. Thus larger ratios reflecting a greater separation of f1 and f2 were more effective in generating DPEs at 1 kHz rather than at 4 kHz. The optimal ratio for 2.5 kHz fell at an intermediate value. Conversely, acoustic distortion-product amplitude as a function of primary-tone level was directly related to the frequency separation of the primary tones. Regardless of the frequency region of the primary tones, smaller f2/f1 ratios were superior in generating DPEs in response to 65-dB stimuli, whereas larger ratios elicited bigger DPEs with primaries at 75 and 85 dB SPL. Within any specific stimulus-parameter combination, individual variability in DPE amplitude was noted. When all stimulus conditions describing the variations in frequency and level were considered, an f2/f1 ratio of 1.22 was most effective in maximizing DPE amplitude.

Dependence of distortion-product otoacoustic emissions on primary levels in normal and impaired ears. II. Asymmetry in L1,L2 space.

Previous studies indicate that the amplitude of 2f1-f2 distortion-product otoacoustic emissions (DPOAEs), evoked by two tones of frequencies f1 < f2, demonstrates a complex dependence on the levels (L1 and L2) of the primary tones. In the present study, 2f1-f2 DPOAE amplitudes were measured over a wide range of L1 and L2 in normal human ears, allowing a systematic, level-dependent asymmetry of DPOAE amplitude in L1,L2 space to be characterized. The L1,L2 at which DPOAEs were largest was close to L1 = L2 at high stimulus levels, but moved monotonically toward L1 > L2 as stimulus levels decreased. A related observation was that DPOAE amplitude had a greater dependence on L1 and on L2. These asymmetries were quantified in normal human ears, and compared to the corresponding asymmetries apparent in data from animal models. Recent studies have demonstrated that the reduction of DPOAE amplitude by cochlear trauma is greater when L1 > L2 than when L1 = L2, suggesting that the reduction of DPOAEs by trauma demonstrates an asymmetry in L1,L2 space that is qualitatively similar to that of normative DPOAE amplitude. To investigate this issue, 2f1-f2 DPOAE amplitudes were measured over a wide range of L1 and L2 in rabbit ears pre- and postinjection of the ototoxic loop-diuretic ethacrynic acid. The results indicate that the asymmetry in L1,L2 space of the reduction of DPOAEs by trauma is both qualitatively and quantitatively similar to the asymmetry in L1,L2 space of normative DPOAE amplitude. Specifically, the L1 values that maximized normative DPOAE amplitudes for any specified L2 (or, equivalently, the L1 values that allowed L2 to be minimized for any specified normative DPOAE amplitude) also yielded the greatest reduction of DPOAEs by the diuretic. In humans, the L1 values that maximize normative DPOAE amplitudes for any specified L2 are well approximated by a simple equation, with parameters that vary with frequency and f2/f1. It is suggested that the L1,L2 values defined by this equation may be optimum for use in clinical applications.

Visualization of the onset of distortion‐product otoacoustic emissions, and measurement of their latency

This paper describes a method for visualization of the onset of distortion-product otoacoustic emission (DPOAE) waveforms in the time domain. The DPOAE waveforms are obtained using ensemble averaging of samples of microphone output. A rectangular sample window is used, and the primary tones are turned on within the sample window. The phases of the primary tones (f1 and f2) are varied systematically between samples in such a way that the primary tones, and all DPOAEs (e.g., 2f2-f1, 3f1-2f2, 2f1), except the DPOAE of interest (e.g., 2f1-f2), are cancelled in the ensemble average. Visualization of the DPOAE onset allows measurement of the onset latency (OSL) of the DPOAE. These direct measurements of OSL are compared to phase-gradient latencies (PGLs) in the same ears determined by measuring the phase change of the DPOAE as a function of DPOAE frequency. The direct measures of OSL vary from > 10 to < 1 ms, decrease with increasing frequency and increasing stimulus level, and are shorter in rabbits than humans. The direct measures of OSL are, in general, quantitatively similar to PGL estimates, but there are exceptions. Visualization of DPOAE onset also allows quantification of DPOAE rise times, and reveals phase and amplitude changes of the DPOAE that occur several milliseconds after onset in rabbits and humans. It is proposed that the phase and amplitude changes result from vector summation of multiple components of the DPOAE signal, each with a different latency.

Effects of cis-platinum chemotherapy on otoacoustic emissions : the development of an objective screening protocol

To develop an objective, fast, and simply performed screening protocol for cis-platinum (CP) ototoxicity, we compared the efficacy of screening with distortion-product otoacoustic emissions (DPOAEs) with the outcome of both conventional and ultra-high-frequency (UHF) audiometry. Baseline audiometric and DPOAE testing was performed in 66 patients, 33 of whom met criteria for inclusion in the final database. Comparisons were made between baseline measurements and those recorded before subsequent CP infusions. Outcomes were analyzed clinically and with paired repeated-measures analysis of variance. Results indicated that DPOAEs and UHF were better measures than conventional audiometry. Further, DPOAEs may be better suited for screening older patients receiving CP chemotherapy because DPOAEs are as sensitive as UHF and are present in a greater number of these patients. Screening with DPOAEs may be enhanced by testing only in the 3- to 5.2-kHz range, thus decreasing testing time. Higher time averages to increase the signal-to-noise ratio and use of this narrower bandwidth might also allow for accurate bedside testing.

Locus of generation for the 2 f1−f2 vs 2 f2−f1 distortion-product otoacoustic emissions in normal-hearing humans revealed by suppression tuning, onset latencies, and amplitude correlations

The present study used distortion-product otoacoustic emission (DPOAE) suppression tuning curves (STCs), DPOAE onset latencies (OLs), and DPOAE amplitude correlations to investigate the locus of generation of the 2f1-f2 DPOAE versus the 2f2-f1 DPOAE in humans. The results of the tuning study revealed that, for the 2f1-f2 DPOAE, the tips of the STCs tuned consistently below the geometric-mean (GM) frequency of the primary tones. In contrast, for the 2f2-f1 DPOAE, STCs tuned above the GM of the primaries, with 50% of the tip frequencies at, or above, the 2f2-f1 frequency place. When the average ratio of the 2f2-f1 to the 2f1-f2 tip frequencies was computed, a factor of 1.44 provided an estimate of the frequency shift needed to align the two DPOAE generation sites. Other results showed that OLs for the 2f2-f1 DPOAE were uniformly shorter than those for the 2f1-f2, with differences at the low frequencies amounting to as much as 6-7 ms. Further, for both DPOAEs, curves describing latency decreases as a function of increasing GM frequencies were best fit by power functions. Shifting the GM frequency producing the 2f2-f1 DPOAE by a factor of 1.6 caused the latency distributions for both DPOAEs to overlap thus resulting in a single function that described cochlear delay as a function of GM frequency. Finally, for each GM frequency in the DP-gram, sliding correlations from 108 normal ears were performed on both DPOAEs by holding the primaries producing the 2f1-f2 DPOAE constant, while all 2f2-f1 DPOAE amplitudes were successively correlated with the 2f1-f2 amplitudes. This procedure demonstrated that, for a given GM frequency producing the 2f1-f2, the correlations between the two DPOAEs peaked when the primaries of the 2f2-f1 were at a GM frequency that positioned the 2f2-f1 frequency place near the GM of the primaries that produced the 2f1-f2 DPOAE. As a whole, the above findings strongly suggest that the 2f2-f1 DPOAE in humans is generated basal to the primary-tone place on the basilar membrane.

Age-related loss of distortion product otoacoustic emissions in four mouse strains.

Changes in cochlear function in four inbred strains of mice, CBA/CaJ (CBA), C57BL/6J (C57), BALB/cByJ (BALB), and WB/ReJ (WB), previously used to study age-related hearing loss, were evaluated serially as a function of age with 2f(1)-f(2) distortion-product otoacoustic emissions (DPOAEs). DPOAE levels in response to equilevel primary tones for geometric-mean (GM) frequencies from 5.6 to 48.5 kHz were recorded systematically as DP-grams and response/growth or input/output (I/O) functions at monthly intervals from about 2 to 15 months of age. Over the approximate 13-month measurement period, CBAs showed robust and unchanged DPOAEs for all tested frequencies, while BALBs, C57s, and WBs showed strain-specific, age-related decreases in DPOAEs that progressed systematically from the high to low frequencies. Specifically, for the youngest WBs at 2 months of age, no DPOAEs were recordable for GM frequencies > or = 32 kHz, while C57s and BALBs reached the identical stage of cochlear dysfunction by 5 and 8 months, respectively. The differential decline in DPOAE activity shown for WB, C57, and BALB mice supports the notion that they represent unique animal models of age-related changes in cochlear function. In contrast, the unchanging DPOAEs for CBAs over the same time period indicate that this strain makes an effective control for normal cochlear function in the mouse, at least, up to 15 months of age.

Suppression and enhancement of distortion-product otoacoustic emissions by interference tones above f2. I. Basic findings in rabbits

The present study measured interference-response areas (IRAs) for distortion-product otoacoustic emissions (DPOAEs) at 2f(1)-f(2), 3f(1)-2f(2), and 2f(2)-f(1). The IRAs were obtained in either awake or anesthetized rabbits, or in anesthetized guinea pigs and mice, by sweeping the frequencies and levels of an interference tone (IT) around a set of f(1) and f(2) primary tones, at several fixed frequencies and levels, while plotting the effects of the IT on DPOAE level. An unexpected outcome was the occurrence of regions of suppression and/or enhancement of DPOAE level when the IT was at a frequency slightly less than to more than an octave above f(2). The IRA of the 2f(1)-f(2) DPOAE typically displayed a high-frequency (HF) lobe of suppression, while the 2f(2)-f(1) emission often exhibited considerable amounts of enhancement. Moreover, for the 2f(2)-f(1) DPOAE, when enhancement was absent, its IRA usually tuned to a region above f(2). Whether or not suppression/enhancement was observed depended upon primary-tone level and frequency separation, as well as on the relative levels of the two primaries. Various physiological manipulations involving anesthesia, eighth-nerve section, diuretic administration, or pure-tone overstimulation showed that these phenomena were of cochlear origin, and were not dependent upon the acoustic reflex or cochlear-efferent activity. The aftereffects of applying diuretics or over-exposures revealed that suppression/enhancement required the presence of sensitive, low-level DPOAE-generator sources. Additionally, suppression/enhancement were general effects in that, in addition to rabbits, they were also observed in mice and guinea pigs. Further, corresponding plots of DPOAE phase often revealed areas of differing phase change in the vicinity of the primary tones as compared to regions above f(2). These findings, along with the effects of tonal exposures designed to fatigue regions above f(2), and instances in which DPOAE level was dependent upon the amount of suppression/enhancement, suggested that the interactions of two DPOAE-generator sources contributed, in some manner, to these phenomena.

Early effects of cerebellopontine angle compression on rabbit distortion-product otoacoustic emissions: a model for monitoring cochlear function during acoustic neuroma surgery.

A rabbit model was developed to simulate the effects of Ischemia that may occur during surgical removal of tumors Involving the cerebellopontine angle or internal auditory canal. Specifically, the internal auditory artery was visualized through a posterior craniotomy and mechanically compressed for repetitive 1-minute intervals with a micromanipulator-controlled glass pipet terminating in a smooth bead. The 2f1-f2 distortion-product otoacoustic emissions were used to monitor the susceptibility of cochlear function to compressive effects. Distortion-product otoacoustic emissions were measured during discrete preblock, block, and postblock periods to determine the time course of distortion-product otoacoustic emission reduction and its return to baseline levels after rapid obstruction and resumption, respectively, of the cochlear vascular supply. Comparisons during these times indicated that preblock distortion-product otoacoustic emission levels were very stable, often varying by less than 1 dB. Additionally, distortion-product otoacoustic emissions were very sensitive to brief vascular occlusions in that, within approximately 25 seconds of blockage onset, emission levels at all frequencies decreased at rates of about − 1.5 dB/second. On alleviation of the occlusion, distortion-product otoacoustic emissions rapidly and completely returned to preblock levels with a delay of about 4 seconds and recovery slopes of about 10.5 dB/second. A notable finding in some animals was that early and reproducible variations in distortion-product otoacoustic emission levels occurred within 5 to 8 seconds of internal auditory artery compression. When present, these transitory changes on distortion-product otoacoustic emission levels acted as early warning signs for vascular compromise of cochlear function.

Nonlinear interactions that could explain distortion product interference response areas.

Suppression and/or enhancement of third- and fifth-order distortion products by a third tone that can have a frequency more than an octave above and a level more than 40 dB below the primary tones have recently been measured by Martin et al. [Hear. Res. 136, 105-123 (1999)]. Contours of iso-suppression and iso-enhancement that are plotted as a function of third-tone frequency and level are called interference response areas. After ruling out order aliasing, two possible mechanisms for this effect have been developed, a harmonic mechanism and a catalyst mechanism. The harmonic mechanism produces distortion products by mixing a harmonic of one of the primary tones with the other primary tone. The catalyst mechanism produces distortion products by mixing one or more intermediate distortion products that are produced by the third tone with one or more of the input tones. The harmonic mechanism does not need a third tone and the catalyst mechanism does. Because the basilar membrane frequency response is predicted to affect each of these mechanisms differently, it is concluded that the catalyst mechanism will be dominant in the high-frequency regions of the cochlea and the harmonic mechanism will have significant strength in the low-frequency regions of the cochlea. The mechanisms are dependent on the existence of both even- and odd-order distortion, and significant even- and odd-order distortion have been measured in the experimental animals. Furthermore, the nonlinear part of the cochlear mechanical response must be well into saturation when input tones are 50 or more dB SPL.

Patterns of evoked otoacoustic emissions associated with acoustic neuromas

Evoked otoacoustic emissions (OAEs) are assumed to reflect healthy outer hair cell function. Over the past few years, evoked OAEs have been shown to be useful as indicators of cochlear hearing loss. Because basic studies have shown that OAEs are extremely sensitive to cochlear anoxia and hypoxia, as well as to the adverse effects of many inner ear diseases, it is possible that these objective tests can provide some insight into the fundamental basis of the hearing loss exhibited by patients with acoustic neuromas.