Ouabain induces apoptotic cell death in type I spiral ganglion neurons, but not type II neurons.

Application of ouabain to the intact round-window (RW) membrane of the gerbil cochlea induces apoptosis in most spiral ganglion neurons (SGNs), leaving a few neurons intact (Schmiedt et al. 2002). Here, physiological measures and immunostaining were used to examine the process of SGN degeneration at 3, 6, 12, and 24 h, 4 days, and 1 and 5 months after ouabain treatment. The few remaining neurons surviving up to 5 months after ouabain treatment were immunoreactive for peripherin, a type II neuron marker. Peripherin-positive cell counts indicate that about 7% of the SGNs in the gerbil cochlea are type II neurons, and these neurons survive intact after ouabain treatment. Ouabain exposure had little effect on the outer hair cell and lateral wall systems, even after a 5 month loss of auditory-nerve function. The cellular locations of cytochrome c, poly (ADP-ribose) polymerase (PARP), and activated caspase 3 were examined in control and ouabain-treated cochleas. A redistribution of cytochrome c in peripherin-negative (type I) neurons was observed at 3 h after ouabain exposure. Degraded PARP and activated caspase 3 were also detected in peripherin-negative SGNs at 6 and 24 h after treatment, respectively. These results suggest that the redistribution of cytochrome c is an early event during apoptosis in type I SGNs and that activation of PARP and caspase 3 are associated with apoptosis in these cells. Calcineurin and NF-kappaB are two important signaling pathways that may modulate cell survival in the central nervous system. Here, we found that calcineurin and NF-kappaB selectively labeled type II neurons. It is speculated that the high levels of calcineurin and NF-kappaB in type II SGNs, as compared with type I SGNs, may play protective roles in enhancing the survival of type II neurons exposed to ouabain.

Effects of chronic furosemide treatment and age on cell division in the adult gerbil inner ear.

Atrophy of the stria vascularis and spiral ligament and an associated decrease in the endocochlear potential (EP) are significant factors in age-related hearing loss (presbyacusis). To model this EP decrease, furosemide was delivered into the round-window niche of young adult gerbils by osmotic pump for seven days, chronically reducing the EP by 30-40 mV. Compound action potential (CAP) thresholds were correspondingly reduced by 30-40 dB SPL at high frequencies. Two weeks after withdrawal of furosemide, the treated ears showed an EP recovery of up to 20-30 mV along with a similar recovery of CAP thresholds. The influence of cell division on furosemide-induced and age-related decline of the EP was examined using a mitotic tracer, bromodeoxyuridine (BrdU). Cell proliferation was examined in three groups: young control, furosemide-treated, and aged cochleas. Sections immunostained for BrdU were bleached with H2O2 to eliminate ambiguities with melanin pigment in the inner ear. Cell types positively labeled for BrdU in all three groups included Schwann cells in Rosenthal's canal; glial cells in the osseous spiral lamina; fibrocytes in the limbus, sacculus, and spiral ligament (SL); epithelial cells in Reissner's and round-window membranes; intermediate cells in the stria vascularis; and vascular endothelial cells. Quantitative analysis showed that the mean number of BrdU-positive (BrdU+) intermediate cells in the stria did not differ significantly among the three groups. In contrast, there was a significant increase of BrdU + fibrocytes in the SL of furosemide-treated animals as compared to the young control group. Moreover, there was a significant decrease in labeled fibrocytes in the aged versus the young ears, particularly among the type II and type IV subtypes. The results suggest that the increased fibrocyte turnover in the SL after furosemide treatment may be related to the recovery of EP and CAP thresholds, supporting the hypothesis that fibrocyte proliferation may be essential for maintaining the EP and cochlear function in normal and damaged cochleas. Moreover, the decreased turnover of SL fibrocytes with age may be a contributing factor underlying the lateral wall pathology and consequent EP loss that often accompanies presbyacusis.

Endocochlear potentials and compound action potential recovery: functions in the C57BL/6J mouse.

The C57BL/6J mouse suffers from cochlear degeneration beginning at an early age and has been used as a model of age-related hearing loss (presbyacusis). Here, the endocochlear potential (EP) and compound action potential (CAP) responses were determined in one-, four-, 12- and 24-month-old C57BL/6J mice. CAP measures included thresholds to tone pips, input/output (I/O) functions, and recovery functions to conditioning tones. EP values among the four age groups did not differ significantly (P>0.05) in either the basal or apical turns. CAP thresholds were increased significantly by 10 to 30 dB in the four-month group compared to the one-month controls at 11.3, 16, 20, and 22.6 kHz. CAP I/O functions were shallower in the four-month group compared to controls at all frequencies. In the 12- and 24-month-old mice, CAP responses were absent, despite normal EP values in these animals. Recovery functions after conditioning tones were obtained at 8, 16, 20 and 22.6 kHz; the functions had fast and slow components at all frequencies tested in both the one- and four-month-old groups. The corresponding recovery curves were identical for both age groups, even with significant threshold shifts in the older group. The two component recovery curves provide the first physiological evidence that different spontaneous rate (SR) classes of auditory neurons exist in the C57BL/6J mouse. Moreover, the unchanged recovery functions in the older group suggest that there was no loss of activity of the low-SR fiber population with age under conditions where the EP remains stable, in contrast to the gerbil model of presbyacusis where there is a loss of low-SR fiber activity and EP does decline with age.

Ouabain application to the round window of the gerbil cochlea: a model of auditory neuropathy and apoptosis.

The physiological and morphological changes resulting from acute and chronic infusion of ouabain onto the intact round-window (RW) membrane were examined in the gerbil cochlea. Osmotic pumps fitted with cannulas allowed chronic (0.5-8 days) infusions of ouabain. Acute and short-term applications of ouabain (1-24 h) induced an increase in auditory-nerve compound action potential (CAP) thresholds at high frequencies with lower frequencies unaffected. The resulting threshold shifts were basically all (no response) or none (normal thresholds), with a sharp demarcation between high and low frequencies. Survival times of 2 days or greater after ouabain exposure resulted in complete auditory neuropathy with no CAP response present at any frequency. Distortion product otoacoustic emissions (DPOAEs) and the endocochlear potential (EP) were largely unaffected by the ouabain indicating normal function of the outer hair cells (OHC) and stria vascularis. One to 3 days after short-term applications, apoptosis was evident among the spiral ganglion neurons assessed both morphologically and with TdT-mediated dUTP-biotin nick end labeling (TUNEL). With 4-8 day survival times, most spiral ganglion cells were absent; however, a few cell bodies remained intact in many ganglia profiles. These surviving neurons had many of the characteristics of type II afferents. Our working hypothesis is that the ouabain induces a spreading depression among the type I ganglion cells by blocking the Na,K-ATPase pump. Because of the constant spike activity of these cells, the ouabain rapidly alters potassium concentrations within ([K+]i) and external to ([K+]o) the ganglion cells, thereby initiating an apoptotic cascade.

Modeling 3-D deformation of outer hair cells and their production of the active force in the cochlea.

We analyze the deformation of the outer hair cell and its production of active force under physiological conditions. The active force has two components. One results from the strain caused by loading in the organ of Corti in the cochlea and depends on the level of the acoustic signal; the other is related to the intrinsic active properties of the cell membrane. We demonstrate our approach by considering, as a basic model of an outer hair cell in the organ of Corti, a cylindrical shell that is filled with an incompressible fluid and located between two planes that move relative to each other. These planes represent the basilar membrane and tectorial membrane complexes. We show that the deformed state of the cell has a 3-D nature, including bending and twisting components. This is different from the experimental conditions in which the active force is usually measured. We estimate the active force as a function of the relative position of the planes, angle of the cell's inclination, and the cell length.

Auditory nerve fibers in young and quiet-aged gerbils: morphometric correlations with endocochlear potential.

The number, size and distribution of myelinated nerve fibers were analyzed in the osseous spiral lamina (OSL) of young and old gerbils raised in a quiet environment. Because decreased endocochlear potentials (EPs) play a significant role in age-related hearing loss in the gerbil, we correlated morphometric and topographical data for nerve fibers with EP measurements in the same ear. Fibers were analyzed at the 2 and 10 kHz locations. The number of fibers at the 2 kHz location ranged from 12 to 47% greater than at the 10 kHz place in both young and aged specimens. No significant correlation was found between the number of fibers and the EP. Nerve fibers in gerbil tend to be distributed vertically by size within the OSL [Slepecky et al. (2000) Hear. Res. 144, 124-134], a result also found in cats and guinea pigs. Smaller fibers are more often found towards the scala vestibuli side of the OSL, whereas larger fibers are concentrated towards the scala tympani. The present data confirmed this distribution in young gerbils; however, in aged ears the distribution often became more uniform. Moreover, fiber distribution and ganglion cell size were highly correlated with EP. As EP declined, the fiber size distribution in the OSL became more uniform and the mean cross-sectional area of spiral ganglion cells and fiber diameter decreased. Thus, for whatever reason, certain indices of auditory nerve fiber morphometrics appear to be associated with the EP.

Fine structure of the 2 f1-f2 acoustic distortion products: effects of primary level and frequency ratios.

The fine structure of the 2 f1-f2 acoustic distortion product (ADP) was measured in humans with different primary level (L1/L2) and frequency (f2/f1, f2 > f1) ratios. The (L1/L2) ratio was varied under two conditions. In the first condition L1 was fixed at 50 dB SPL while L2 was varied from 30 to 75dB SPL in 5-dB steps. An upward frequency shift was observed in the ADP fine structure as L2 was increased. In the second condition, L2 was fixed at 50 dB SPL and L1 varied, and a downward frequency shift was observed. These opposing frequency shifts are predicted by a vector-sum model [Sun et al., J. Acoust., Soc. Am. 96, 2166-2174, 2175-2183 (1994)] and support the hypothesis that the ADP fine structure largely reflects place features of the area of overlap of the primary traveling waves. The mechanisms underlying the shifts in fine structure were further investigated by using three primary f2/f1 ratios: 1.11, 1.2, and 1.33. An orderly difference in the rate of fine-structure shift with level was observed as a function of f2/f1 ratio, with the largest rate of shift associated with the smallest frequency ratio. This observation, along with the fact that downward frequency shift (with L1 varied) is always at a larger rate than the upward shift (with L2 varied), suggests that ADP levels and fine structure are strongly influenced by the nonlinear compression present in the mechanics of the basilar membrane in the region of overlap between the primary traveling waves.

Decline in the endocochlear potential corresponds to decreased Na,K-ATPase activity in the lateral wall of quiet-aged gerbils.

The ion transport-mediating enzyme, Na,K-ATPase, is abundantly present in the cochlear lateral wall. This enzyme is essential for the generation and maintenance of the endocochlear potential. Diminished enzyme activity has been observed previously in the lateral wall of quiet-aged gerbils. The present study was designed to investigate the impact of the age-related decline in Na,K-ATPase specific activity upon auditory function. Measures of the resting endocochlear potential value and the level of Na,K-ATPase specific activity were made in cochleae obtained from gerbils aged in quiet conditions. Analysis revealed a high degree of correspondence between the level of lateral wall Na,K-ATPase specific activity and the value of the endocochlear potential measured in the round window/turn 1 region of the cochlea. Nonlinear regression models showed a strong relationship between the age-related reductions in enzyme activity and the magnitude of the endocochlear potential. The data suggest that during metabolic presbyacusis a decrease in Na,K-ATPase specific activity can explain most, but not all, of the decline in the endocochlear potential.

Effects of aging on potassium homeostasis and the endocochlear potential in the gerbil cochlea.

Previous work has shown that the endocochlear potential (EP) decreases with age in the gerbil. Concomitant with the EP decrease is an age-related loss of activity of Na,K-ATPase in the lateral wall and stria vascularis. We hypothesized that the EP decrease is associated with a similar decrease in the endolymphatic potassium concentration [Ke+]. This hypothesis was tested using double-barrelled, K(+)-selective electrodes introduced into scala media through the round window in young and quiet-aged gerbils. Results show that the means (+/- S.D.) of the [Ke+] in young and aged gerbils were not significantly different (178.2 +/- 14.2 mM and 171.2 +/- 34.4 mM, respectively), although the intersubject variability was much greater in the aged animals than in the young. These values of [Ke+] are slightly higher than those found for other mammals and may reflect the higher plasma osmolarity found in the gerbil. The concentration of perilymphatic potassium [Kp+] in scala tympani at the round window was also similar for the young and aged groups (3.57 +/- 1.17 mM and 4.18 +/- 2.03 mM, respectively). On the other hand, mean EP values in the young and aged gerbils were 92.0 +/- 5.7 mV and 64.8 +/- 15.8 mV, respectively and were statistically different (P < 0.001). Overall, EP and [Ke+] showed little correlation (R2 = 0.23), except that when [Ke+] fell below 150 mM, the EP was always less than 60 mV. An analysis of the chemical potential for Ke+ with respect to Kp+ shows that it was similar for young and aged gerbils (overall mean of 103.1 +/- 13.7 mV) and remained constant with respect to the EP, in spite of an overall electrochemical potential of Ke+ that varied from 120 to 210 mV. Thus, the system maintains Ke+ homeostasis at the expense of the EP, even when the EP is on the verge of collapse.

Age-related decreases in endocochlear potential are associated with vascular abnormalities in the stria vascularis.

The density and diameter of strial capillaries were assessed in whole-mount preparations of the cochlear lateral wall from 18 gerbils aged in quiet for at least 36 months. Following morphometric analysis, histopathologic changes in selected regions of the lateral wall were examined by light and transmission electron microscopy. Alterations in strial vasculature were compared with the endocochlear potential (EP) measurements from the same ear. Vascular degeneration occurred in a segmental fashion in that regions of atrophic capillaries were found throughout the cochlea but primarily in the apical and lower basal turns and in the hook. The amount of stria with normal capillaries varied greatly among the aged ears, ranging from 19 to 87%. The resting EP also varied markedly, ranging from 23 to 83 mV. Little correlation was found between vascular alterations and the corresponding EP value from individual cochlear turns. However, significant correlations were found between the total strial area with normal vasculature and both the mean EP value and that recorded at either the round window or first turn in that ear.

Measures of tuning and suppression in single-fiber and whole-nerve responses in young and quiet-aged gerbils.

Tuning and suppression were examined in the auditory nerves of young-control and quiet-aged gerbils. Tuning curves obtained from single-fiber responses were compared to those obtained with the compound action potential (CAP) using masking procedures. Tuning was measured in terms of the high-frequency slope of the tuning curve and Q values obtained 10 dB and 40 dB (Q10 dB and Q40 dB, respectively) above the threshold at its best frequency. The study had two objectives: first, how CAP measures of tuning and suppression correspond to single-fiber measures in presbyacusic cochleas; and second, how the above measures of tuning change with age without the confounding effects of noise exposure. It was found that measures derived from the CAP responses in aged gerbils remained similar to the trends of the single-fiber data, despite the many morphological changes that are known to occur in the presbyacusic ear. Thus, CAP procedures remain an appropriate alternative to single-fiber recording in aged animals where the stability of the preparation can be tenuous. With regard to tuning and suppression, our results show that single-fiber and CAP tuning curves in quiet-aged animals are similar to those of young controls except for higher thresholds near the best frequency. The tail response remained largely stable with age, and no instances of tail hypersensitivity were found. The slopes of the high-frequency legs of the curves were similar in young and aged animals, and were associated with the presence of two-tone suppression on the high-frequency side. In a few instances high-side suppression was absent in the aged gerbils and was associated with tuning curves with shallow high-frequency slopes and characteristic frequency (CF) threshold shifts of 30 dB or greater. Mean high-frequency slopes and Q values increased with best frequency in young controls, but were fairly constant with best frequency in quiet-aged animals. Thus, in comparison to controls, the frequency selectivity of quiet-aged gerbils tends to decrease somewhat at frequencies above 4 kHz. Many of these changes with age may be ascribed to a chronic decline of the endocochlear potential (EP) acting on an intact hair-cell system in quiet-aged gerbils. With this assumption, CF thresholds are most sensitive to the EP decline, whereas boundaries of tuning and two-tone suppression taken at more intense levels are least affected.

Age-related loss of activity of auditory-nerve fibers.

1. Characteristic frequencies (CF), spontaneous rates (SR), and thresholds were recorded from single fibers in the auditory nerves of gerbils aged for 36 mo in a quiet vivarium. The data from the quiet-aged animals were compared with similar data obtained previously from young controls. Fibers were classified as "low-SR" if their spontaneous rates were < or = 18 spikes/s and "high SR" for higher rates. 2. For CFs > 6 kHz, the percentage of low-SR fibers contacted declined from 57% of the population in young gerbils to 29% in the aged gerbils. This population change is statistically significant (P < 0.01). At CFs < 6 kHz, the population demographics did not change significantly with age, with the low-SR fibers comprising 30 and 39% of the population, respectively, for the young and aged animals. 3. To further test the hypothesis that low-SR fibers with CFs > 6 kHz become less active with age, additional experiments were conducted to examine the recovery of the compound action potential (CAP) response from prior high-level stimuli. Previous work has shown that the CAP recovery curve has two segments: a fast segment associated with the high-SR fibers and a slow segment associated with the low-SR fibers. The curves obtained from quiet aged gerbils show a faster recovery than young controls for probe tones at 8 and 16 kHz, but not at 2 and 4 kHz. Thus these results agree with our single-fiber data indicating that there is a loss of low-SR activity for CFs > 6 kHz in the aged animals. 4. Low-SR fibers typically have larger dynamic ranges than those of high-SR fibers, are better able to preserve information concerning stimulus timing and amplitude modulation, and their responses are more robust in the presence of masking noise. Moreover, low-SR fibers are likely inputs to the crossed-olivocochlear reflex, a reflex that serves an antimasking role in the detection of sounds in a binaural noise field. If true for humans, the loss of the low-SR system could explain many of the hearing deficits often seen in older individuals; e.g., decreased ability to understand speech in noise, changes in masking level differences, and decreased ability to localize sound sources using binaural cues.

Age-related decreases in endocochlear potential are associated with vascular abnormalities in the stria vascularis.

The density and diameter of strial capillaries were assessed in whole-mount preparations of the cochlear lateral wall from 18 gerbils aged in quiet for at least 36 months. Following morphometric analysis, histopathologic changes in selected regions of the lateral wall were examined by light and transmission electron microscopy. Alterations in strial vasculature were compared with the endocochlear potential (EP) measurements from the same ear. Vascular degeneration occurred in a segmental fashion in that regions of atrophic capillaries were found throughout the cochlea but primarily in the apical and lower basal turns and in the hook. The amount of stria with normal capillaries varied greatly among the aged ears, ranging from 19 to 87%. The resting EP also varied markedly, ranging from 23 to 83 mV. Little correlation was found between vascular alterations and the corresponding EP value from individual cochlear turns. However, significant correlations were found between the total strial area with normal vasculature and both the mean EP value and that recorded at either the round window or first turn in that ear.

Effects of aging on the fine structure of the 2f1-f2 acoustic distortion product.

The fine structures of 2f1-f2 acoustic distortion products (ADP) were measured in four groups of human subjects: (1) young with normal hearing, (2) aged with normal or near-normal hearing, (3) aged subjects with more severe hearing loss above 2000 Hz, and (4) young with hearing similar to those of the normal- or near-normal-hearing aged group. The purpose of this study was to investigate how ADP fine structure changes with age and hearing loss. Results show that the fine structure is observable whenever the ADP is measurable, and its sharpness, defined as the peak-to-peak frequency distance, is independent of age hearing loss, and longitudinal amplitude change. There is a large variance in ADP peak amplitudes in aged subjects with or without hearing loss as compared to young normal hearing subjects, the aged group generally having lower peak amplitudes than those of the young group. According to an ANOVA analysis with absolute threshold as covariate, the null hypothesis stating that there is no aging effect on the ADP peak responses cannot be ruled out, a conclusion similar to that made by Stover and Norton [J. Acoust. Soc. Am. 94, 2670-2681 (1993)]. On the other hand, threshold changes cannot explain all the differences in ADP amplitude. It is clear that the relationship between ADP amplitudes and behavioral thresholds can differ between young and aged populations. At primary levels of 50 dB SPL, almost normal ADP magnitudes are often found in aged subjects even when associated with a 35-dB hearing loss, whereas for young subjects ADPs typically were not measurable when associated with the pure-tone thresholds of 20 dB HL or higher. This dichotomy may be explained by the different etiologies of cochlear pathologies predominant in the two groups.

Distortion-product otoacoustic emissions in Mongolian gerbils with resistance to noise-induced hearing loss.

Distortion-product otoacoustic emissions (DPOAEs) and the endocochlear potential (EP) were recorded in adult Mongolian gerbils exposed to noise for either 1 or 12 days. The exposure was an octave band of noise centered at 4 kHz at 80 dB SPL with a duty cycle of 6 h on, 18 h off. A previous study showed that a single such exposure causes 20-50 dB of temporary threshold shift (TTS) in the neural response at 4-8 kHz, but that the TTS is reduced to less than 10 dB following 12 daily exposures [Boettcher, J. Acoust. Soc. Am. 94, 3207-3214 (1993)]. This reduction in TTS is commonly referred to as resistance to noise-induced hearing loss (NIHL). To further analyze whether resistance to NIHL is caused by changes in the outer hair cell (OHC) system or the lateral wall system (or both), DPOAEs and EPs were measured in the exposed ears. The amplitudes of DPOAEs were significantly reduced in the frequency region from 4 to 10 kHz in subjects exposed to noise for 1 day, but were relatively normal in subjects exposed for 12 days. DPOAE amplitudes from frequency regions below the spectrum of the exposure were similar across the exposure and control groups except at the low-frequency edge of the noise where DPOAE amplitudes were consistently higher than normal in the exposed animals. The EP values in both exposure groups were not reduced from normal, unexposed levels. Thus there was no causal relationship between changes in the EP and the reduction of the DPOAE amplitudes. These data suggest that the development of resistance to noise is related to an initial depression of OHC activity followed by a recovery of activity to a stable level, despite an ongoing exposure.

Masking of auditory brainstem responses in young and aged gerbils.

Auditory brainstem responses (ABR) were recorded in the presence of low-pass (1 kHz cutoff) or high-pass (8 kHz cutoff) filtered noise in young (4-8 month) and aged (36 month) gerbils. For low-pass maskers, aged gerbils had higher masked thresholds at 2 and 4 kHz than young subjects. This was true for all aged subjects, including those with quiet thresholds similar to those of young controls. For high-pass masking, the majority of aged subjects had higher masked thresholds at 2 and 4 kHz than young controls; however, aged subjects with relatively normal quiet thresholds had masked thresholds similar to those of young subjects. A modified power-law (MPL) model was used to predict masked thresholds for aged subjects. Thresholds measured in the presence of low-pass noise were higher than predicted in many of the aged subjects, particularly those with near-normal quiet thresholds. In contrast, thresholds measured in the presence of the high-pass masker were similar to the predicted thresholds. These results suggest that: (a) excess masking occurred in aged subjects for low-pass, but not high-pass, maskers; (b) the excess masking occurred independently of quiet thresholds; and (c) excess upward spread of masking was related to the spectrum of the masker and not the 2 and 4 kHz regions of the auditory periphery.

Development of cochlear potentials in the neonatal gerbil.

The onset and maturation of hearing was examined in separate groups of sibling and nonsibling neonatal Mongolian gerbils (Meriones unguiculatus). Auditory nerve compound action potentials (CAP) and cochlear microphonics (CM) were measured at the round window, and the endocochlear potential (EP) was recorded at three different locations in pups aged 13 to 30 days after birth (DAB) and in 90 day-old animals. Maturational trends for the three potentials were similar to those previously reported for gerbil neonates. However, CAP thresholds continued to decrease, and CM and CAP input/output functions and EP continued to increase beyond 30 days of age, a time at which many investigators have considered hearing in the gerbil to be mature. The EP developed simultaneously throughout the cochlea and approached 80 mV by 20 DAB. CAP thresholds showed a highly correlated log-linear relationship with EP in groups of nonlittermates and in siblings studied at different ages. In contrast, maximum CAP and CM amplitudes increased with increasing EP, but did not show significant growth until the EP exceeded 70 mV.

Modeling the fine structure of the 2f1-f2 acoustic distortion product. I. Model development.

The fine structure of the 2f1-f2 acoustic distortion product (ADP) as a function of frequency has been measured in human subjects and shows a series of sharp peaks and valleys (rippling) with peak-to-valley level differences of up to 15-20 dB. In order to delineate the cause of the ADP rippling pattern, a computer model was developed to simulate the behavior of the ADP, specifically the ADP fine structure. The ADP model includes the middle ear and cochlea. The middle ear was treated as a simple signal delivery system in both the forward and reverse directions. The ADP was assumed to be generated within the cochlea by nonlinear elements taken to be the outer hair cells (OHCs), and an array of ADP generators was used to simulate the OHCs along the basilar membrane (BM). The magnitude and phase of the output of each of the ADP generators were functions of the local responses of the two primary traveling waves. The traveling waves were calculated from a passive transmission line model of the BM using the WKB approximation, coupled to a second-order resonance to mimic the contribution from active OHC feedback. The system output of ADP in dB was proportional to the weighted vectorial sum of all the components, arriving at the stapes. Parameters such as lateral coupling and feedback gain were examined.

Modeling the fine structure of the 2f1-f2 acoustic distortion product. II. Model evaluation.

In a previous article, a vector sum model was developed that successfully reproduces the ADP rippling pattern when a nonuniformity is introduced in the active damping factor, a parameter that is inversely related to the energy gain contribution of the outer hair cells [OHCs, Sun et al., J. Acoust. Soc. Am. 96, 2166-2174 (1994)]. Here, the mean of the damping factor is increased nonlinearly with input level, mimicking the saturation of the active feedback of the OHCs. The passive damping factor in the transmission line model was also nonlinearly increased with input level to reproduce the frequency shift of the peak of the traveling wave observed in experimental data. The resulting model simulates an ADP that is compatible with data from human subjects wherein the ADP fine structure does not saturate with level. Moreover, the model suggests that the shifting of the ADP pattern with level is a direct result of the peak shift of the traveling wave, thus implicating the nonlinear damping factors as the underlying basis of this phenomenon. The input/output (I/O) functions of the simulated ADP emissions at specific frequencies were also examined. The resulting functions show a variety of shapes, depending on the pattern of ADP fine structure around the I/O frequency, and the way the fine structure shifts as primary levels increase. These I/O functions are also similar to those observed in human subjects, even with regard to overall slopes which approximate one. Thus the model illustrates how cubic distortion generators coupled with damping on linearities can yield I/O function slopes on the order of one, rather than the expected three.(ABSTRACT TRUNCATED AT 250 WORDS)