Distribution of focal lesions in the chinchilla organ of Corti following exposure to a 4-kHz or a 0.5-kHz octave band of noise.

An octave band of noise (OBN) delivers fairly uniform acoustic energy over a specific range of frequencies. Above and below this range, energy is at least 30 dB SPL less than that within the OBN. When the ear is exposed to an OBN, hair-cell loss often occurs outside the octave band. The frequency location of hair-cell loss is evident when the percent distance from the apex of focal lesions is analyzed. Focal lesions involve substantial loss of outer hair cells (OHCs) only, inner hair cells (IHCs) only, or both OHCs and IHCs (i.e., combined lesions) in a specific region of the organ of Corti (OC). Data sets were assembled from our permanent collection of noise-exposed chinchillas as follows: (1) the sum of exposure duration and recovery time was less than or equal to 11 d; (2) the exposure level was less than or equal to 108 dB SPL; and (3) focal lesions were less than 1.5mm in length. The data sets included a variety of exposures ranging from high-level, short duration to moderate-level, moderate duration. The center of each focal lesion was expressed as percent distance from the OC apex. Means, standard deviations and medians were calculated for focal-lesion size resulting from exposure to a 4-kHz or a 0.5-kHz OBN. Histograms were then constructed from the percent-location data using 2.0% bins. For the 4-kHz OBN, 5% of the lesions were in the apical half of the OC and 95% were in the basal half. The mean lesion size was 1.68% of total OC length for OHC and combined focal lesions and 0.42% for IHC focal lesions. Most OHC and combined lesions occurred in the 5-7-kHz region, at and just above the upper edge of the OBN. Clusters of lesions were also found around 8 and 12 kHz. A cluster was present at and just below the lower edge of the OBN, as well as another in the 1.5-kHz region. For the 0.5-kHz OBN, 34% of the lesions were in the apical half of the OC and 66% were in the basal half. The mean lesion size was 0.93% for OHC and combined focal lesions and 0.32% for IHC focal lesions. OHC and combined focal-lesion distribution showed clusters at 0.25, 0.75 and 1.5 kHz in the apical half of the OC. In the basal half, the distribution of focal lesions was similar to that seen with the 4-kHz OBN (r=0.54). With both OBNs, most IHC focal lesions occurred in the basal half of the OC. High resolution power spectrum analysis of each OBN and non-invasive tests for harmonics and distortion products in a chinchilla were performed to look for exposure energy above and below the OBN. No energy was found that could explain the OC damage.

Effects of intense noise exposure on the outer hair cell plasma membrane fluidity.

Outer hair cells (OHCs) play an important role in cochlear amplification via their length changes (electromotility). A noise-induced cochlear amplification loss leading to a permanent threshold shift (PTS) was observed without a significant hair cell loss in rats [Chen, G.D., Liu, Y., 2005. Mechanisms of noise-induced hearing loss potentiation by hypoxia. Hear. Res. 200, 1-9.]. Since motor proteins are inserted in the OHC lateral membrane, any change in the OHC plasma membrane may result in a loss of OHC electromotility, leading to a loss of cochlear amplification. In this study, the lateral diffusion in the OHC plasma membrane was determined in vitro in guinea pigs by fluorescent recovery after photobleaching (FRAP) after an in vivo noise exposure. The lateral diffusion in the OHC plasma membrane demonstrated a length-dependence, which increased as OHC length increased. A reduction in the lateral diffusion was observed in those OHCs with lengths of 50-70 microm after exposure to an 8-kHz octave band noise at 110 dB SPL for 3h. This membrane fluidity change was associated with the selective PTS at frequencies around 8 kHz. The reduction of the lateral diffusion in the OHC lateral wall indicated that noise could impair the micromechanics of the OHC lateral wall and might consequently impair OHC electromotility to induce threshold shift.

Death pathways in noise-damaged outer hair cells.

Using morphological criteria, death pathways in outer hair cells (OHCs) were determined in chinchilla organs of Corti that had been exposed to a high- or moderate-level octave band of noise (OBN) centered at either 0.5 or 4-kHz. The specimens were part of our large collection of plastic-embedded flat preparations of chinchilla cochleae. Three death pathways were identified: (1) oncotic - swollen, pale-staining cell with a swollen nucleus, (2) apoptotic - shrunken, dark-staining cell with a pyknotic nucleus and (3) a newly defined third pathway - no basolateral plasma membrane but cellular debris arranged in the shape of an intact OHC with a nucleus deficient in nucleoplasm. To minimize the secondary loss of OHCs from the entrance of endolymph into the organ of Corti, the specimens used for quantitative analysis of death pathways had the following characteristics: (1) the level to which they were exposed was less than or equal to 95dB SPL, (2) the exposure duration was 6-216h, (3) fixation for microscopic examination took place in vivo 1-2h post-exposure and (4) there were no focal OHC lesions in the organs of Corti. Fifty-eight noise-exposed cochleae met these criteria. In these specimens, degenerating and missing OHCs were classified as to which death pathway the cells had followed or were following. Nine non-noise-exposed cochleae were also evaluated for OHC death pathways. The number of OHCs following the third death pathway was significantly greater in the noise-exposed cochleae than the non-noise-exposed cochleae for total exposure energies greater than those produced by 75dB SPL for 216h to a 0.5-kHz OBN and 57dB SPL for 48h to a 4-kHz OBN. In cochleae exposed to either octave band, OHCs dying by oncosis or apoptosis were uncommon.

The fate of outer hair cells after acoustic or ototoxic insults.

In epithelial sheets, clearance of dead cells may occur by one of several routes, including extrusion into the lumen, phagocytic clearance by invading lymphocytes, or phagocytosis by neighboring cells. The fate of dead cochlear outer hair cells is unclear. We investigated the fate of the "corpses" of dead outer hair cells in guinea pigs and mice following drug or noise exposure. We examined whole mounts and plastic sections of normal and lesioned organ of Corti for the presence of prestin, a protein unique to outer hair cells. Supporting cells, which are devoid of prestin in the normal ear, contained clumps of prestin in areas of hair cell loss. The data show that cochlear supporting cells surround the corpses and/or debris of degenerated outer hair cells, and suggest that outer hair cell remains are phagocytosed by supporting cells within the epithelium.

Extremely rapid induction of outer hair cell apoptosis in the chinchilla cochlea following exposure to impulse noise.

We have reported the presence of OHC apoptosis and necrosis in the organ of Corti following exposure to intense noise. The current study was designed to investigate the rapidity and the initial pattern of outer hair cell (OHC) death induced by exposure to impulse noise. Chinchillas were exposed to 75 pairs of impulse noise at 155 dB peak sound pressure level presented over a time period of 75 s. At 5 or 30 min after the noise exposure, the cochleae were examined for morphological and biological indicators of apoptosis and necrosis. In the cochleae collected within 5 min after the 75-s noise exposure, there were clear signs of nuclear condensation and cell body shrinkage, suggesting the presence of OHC apoptosis. Apoptotic OHCs were further detected by positive staining of TUNEL and caspase-3 assays. In contrast to the rapid development of nuclear condensation, appearance of nuclear swelling, a necrotic phenotype, appeared at 30 min after the noise exposure. The results of the study demonstrate that induction of OHC apoptosis after the noise exposure is an extremely rapid process.

Round window gentamicin application: an inner ear hair cell damage protocol for the mouse.

It is important to develop an inner ear damage protocol for mice that avoids systemic toxicity and produces damage in a relatively rapid fashion, allowing for study of early cellular and molecular mechanisms responsible for hair cell death and those that underlie the lack of hair cell regeneration in mammals. Ideally, this damage protocol would reliably produce both partial and complete lesions of the sensory epithelium. We present a method for in vivo induction of hair cell damage in the mouse via placement of gentamicin-soaked Gelfoam in the round window niche of the inner ear, an adaptation of a method developed to study hair cell regeneration in chicks. A total of 82 subjects underwent the procedure. Variable doses of gentamicin were used (25, 50, 100 and 200 microg). Saline-soaked Gelfoam, sham-operations and the contralateral, non-operated cochlea were used as controls. Survival periods were 1, 3 and 14 days. Damage was assessed on scanning electron microscopy. We found that this method produces relatively rapid hair cell damage that varies with dose and can extend the entire length of the sensory epithelium. In addition, this protocol produces no systemic toxicity and preserves the contralateral ear as a control.

The clinical free radical scavenger, edaravone, protects cochlear hair cells from acoustic trauma.

It is known that reactive oxygen species have toxicity to the cochlea. We investigated the effect of edaravone, a free radical scavenger for clinical use, on the cochleae of guinea pigs subjected to acoustic trauma. We assessed auditory brainstem response (ABR) thresholds to evaluate cochlear function and observed the sensory epithelium. After noise exposure (130 dB SPL, 3 h), we observed that the auditory brainstem response threshold shift in edaravone-treated ears was significantly less than that in untreated ears. This result suggests that edaravone protected the cochleae from acoustic trauma.

The caspase pathway in noise-induced apoptosis of the chinchilla cochlea.

We previously reported that intense noise exposure causes outer hair cell (OHC) death primarily through apoptosis. Here we investigated the intracellular signal pathways associated with apoptotic OHC death. Chinchillas were exposed to a 4 kHz narrowband noise at 110 dB SPL for 1 h. After the noise exposure, the cochleas were examined for the activity of each of three caspases, including caspase-3, -8, or -9 with carboxyfluorescein-labeled fluoromethyl ketone (FMK)-peptide inhibitors. The cochleas were further examined for cytochrome c release from mitochondria by immunohistology and for DNA degradation by the TUNEL method. The results showed that the noise exposure triggered activation of caspase-3, an important mediator of apoptosis. The noise exposure also caused the activation of caspase-8 and caspase-9, each of which is associated with a distinct signaling pathway that leads to activation of caspase-3. Caspase activation occurred only in the apoptotic OHCs and not in the necrotic OHCs. These results indicate that multiple signaling pathways leading to caspase-3 activation take place simultaneously in the apoptotic OHCs. In addition to caspase activation, noise exposure caused the release of cytochrome c from mitochondria, resulting in a punctate fluorescence in the cytosol. In contrast to activation of caspases, the release of cytochrome c took place in both apoptotic and necrotic OHCs. Moreover, the release of cytochrome c in a subpopulation of OHCs took place early in the cell death process, prior to any outward signs of necrosis or apoptosis. These data suggest that in this subpopulation there exists a common step that is shared by cell death pathways before entering either necrosis or apoptosis. Lastly, use of the TUNEL assay in combination with PI labeling provides a more accurate discrimination between apoptosis and necrosis.

Protection from acoustic trauma is not a primary function of the medial olivocochlear efferent system.

The medial olivocochlear (MOC) efferent system is an important component of an active mechanical outer hair cell system in mammals. An extensive neurophysiological literature demonstrates that the MOC system attenuates the response of the cochlea to sound by reducing the gain of the outer hair cell mechanical response to stimulation. Despite a growing understanding of MOC physiology, the biological role of the MOC system in mammalian audition remains uncertain. Some evidence suggests that the MOC system functions in a protective role by acting to reduce receptor damage during intense acoustic exposure. For the MOC system to have evolved as a protective mechanism, however, the inner ears of mammals must be exposed to potentially damaging sources of noise that can elicit MOC-mediated protective effects under natural conditions. In this review, we evaluate the possibility that the MOC system evolved to protect the inner ear from naturally occurring environmental noise. Our survey of nonanthropogenic noise levels shows that while sustained sources of broadband noise are found in nearly all natural acoustic environments, frequency-averaged ambient noise levels in these environments rarely exceed 70 dB SPL. Similarly, sources reporting ambient noise spectra in natural acoustic environments suggest that noise levels within narrow frequency bands are typically low in intensity (<40 dB SPL). Only in rare instances (e.g., during frog choruses) are ambient noise levels sustained at moderately high intensities (~70-90 dB SPL). By contrast, all experiments in which an MOC-mediated protective effect was demonstrated used much higher sound intensities to traumatize the cochlea (100-150 dB SPL). This substantial difference between natural ambient noise levels and the experimental conditions necessary to evoke MOC-mediated protection suggests that even the noisiest natural acoustic environments are not sufficiently intense to have selected for the evolution of the MOC system as a protective mechanism. Furthermore, although relatively intense noise environments do exist in nature, they are insufficiently distributed to account for the widespread distribution of the MOC system in mammals. The paucity of high-intensity noise and the near ubiquity of low-level noise in natural environments supports the hypothesis that the MOC system evolved as a mechanism for "unmasking" biologically significant acoustic stimuli by reducing the response of the cochlea to simultaneous low-level noise. This suggested role enjoys widespread experimental support.

Rescue of auditory hair cells from aminoglycoside toxicity by Clostridium difficile toxin B, an inhibitor of the small GTPases Rho/Rac/Cdc42.

The hair cells (HCs) are the most vulnerable elements in the cochlea and damage to them is the most common cause of sensorineural hearing loss. Understanding the intracellular events that lead to the death of HCs is a key to developing protective strategies. Recently, it has been shown that the c-Jun-N-terminal kinase (JNK) pathway is activated in HCs in response to aminoglycosides (J. Neurosci. 20 (2000) 43). We have studied the upstream events leading to JNK activation in aminoglycoside toxicity in vitro. The small GTPases Rac and Cdc42 are well known upstream activators of JNK in other cell types. Clostridium difficile toxin B monoglucosylates all members of the Rho GTPase subfamily (Rho, Rac and Cdc42 isoforms) and inhibits GTP binding by steric interference (Nature 341 (1989) 209). Organ of Corti explants from p5 rat basal turns were maintained in tissue culture and treated with C. difficile toxin B for 12 h. They were then treated with toxin B plus gentamicin for 72 h. Significantly less HC death was observed compared to with gentamicin alone. Toxin B alone had no effect on HCs at the highest concentration used. Using antibodies against phospho-c-Jun, we observed background immunoreactivity in control explants, strong staining of outer hair cell nuclei in gentamicin treated explants, and weaker immunostaining in explants treated with gentamicin and C. difficile toxin B. We conclude that Rho family small GTPases play a role in aminoglycoside toxicity signaling as upstream activators of the JNK signaling pathway.

Leupeptin protects cochlear and vestibular hair cells from gentamicin ototoxicity.

Calpains, a family of calcium-activated proteases that breakdown proteins, kinases, phosphatases and transcription factors, can promote cell death. Since leupeptin, a calpain inhibitor, protected against hair cell loss from acoustic overstimulation, we hypothesized that it might protect cochlear and vestibular hair cells against gentamicin (GM) ototoxicity. To test this hypothesis, mouse organotypic cultures from the cochlea, maculae of the utricle and the crista of the semicircular canal (P1-P3) were treated with different doses of GM (0.1-3 mM) alone or in the presence of leupeptin (0.1-3 mM). The percentage of outer hair cells (OHCs) and inner hair cells (IHCs) decreased with increasing doses of GM between 0.1 and 3 mM. The addition of 1 mM of leupeptin significantly reduced GM-induced damage to IHCs and OHCs; this protective effect was dose-dependent. GM also significantly reduced hair cell density in the crista and utricle in a dose-dependent manner between 0.1 and 3 mM. The addition of 1 mM of leupeptin significantly reduced hair cell loss in the crista and utricle for GM concentrations between 0.1 and 3 mM. These results suggest that one of the early steps in GM ototoxicity may involve calcium-activated proteases that lead to the demise of cochlear and vestibular hair cells.

Partial recovery of cisplatin-induced hearing loss in the albino guinea pig in relation to cisplatin dose.

The objective of the present study was to further characterize cochlear recovery after cisplatin damage. We equipped albino guinea pigs with permanent round window electrodes. Cisplatin was injected i.p. on a daily basis at either 1.5 or 2.0 mg/kg/day. Treatment was stopped when the criterion of > or =40 dB loss in the compound action potential iso-response level at 8 kHz had occurred. Either shortly (1-3 days) or long (4 weeks or more) after this stop, the endocochlear potential (EP) was measured and all animals were sacrificed for histology. At a cisplatin dose of 2.0 mg/kg/day, the time needed to reach the criterion hearing loss varied from 5 to 11 days. With 1.5 mg/kg/day this period lasted longer, the cumulative dose being the first-order predictor. The cochlear potentials gradually recovered in the first 2 weeks after treatment. At the lower frequencies, recovery was often complete. At the higher frequencies complete recovery was never seen. EP was depressed when measured just after treatment but had normal values long after. Basal outer hair cell (OHC) loss was found for both the short and the long post-treatment period. Thus, loss and recovery of cochlear potentials can for a large part be explained by loss and recovery of the EP. Recovery is limited by permanent OHC loss.

Furosemide alters nonlinear capacitance in isolated outer hair cells.

The outer hair cell (OHC) from the organ of Corti plays a crucial role in hearing through its unique voltage-dependent mechanical responses. Furosemide, one of the loop diuretics, disrupts normal cochlear function. Here we report on direct effects of furosemide on OHC motility-related, voltage-dependent capacitance using the whole-cell patch-clamp technique. Extracellularly applied furosemide reversibly shifted the voltage at peak capacitance (V(pkC(m))) to positive levels. The shift, whose maximum approached 90 mV, evidenced a Hill coefficient of 1.5 and K(1/2) of 10 mM. Changes in the magnitude of nonlinear capacitance were not fully reversible. While it is clear that the overwhelming effect of furosemide on hearing results via its effects on the endolymphatic potential, the present results indicate that furosemide directly alters OHC motility and may, in part, contribute to sensory dysfunction.

Differential vulnerability of basal and apical hair cells is based on intrinsic susceptibility to free radicals.

The base of the cochlea is more vulnerable to trauma than the apex as seen in the pattern of hair cell damage by cisplatin or aminoglycosides. The differential vulnerability is maintained in organotypic cultures exposed directly to these drugs, suggesting there may be an intrinsic difference in sensitivity to damage along the cochlear spiral. We therefore investigated the survival capacity of isolated outer hair cells and strips dissected from different turns of the guinea pig organ of Corti in short-term culture. Cells were stained with fluorescent indicators of viable or dead cells, calcein-AM and ethidium homodimer. After 5 h at room temperature, up to 90% of outer hair cells from the apex survived, but less than 30% from the base. In contrast, basal inner hair cells remained viable, and supporting cells survived for at least 20 h. The difference in survival capacity between basal and apical outer hair cells coincided with a significantly lower level of the antioxidant glutathione in basal outer hair cells compared with apical outer hair cells. This suggested that basal outer hair cells may be more vulnerable to free-radical damage than apical outer hair cells. The survival of basal outer hair cells was significantly improved by addition of the radical scavengers n-acetyl cysteine, p-phenylenediamine, glutathione, mannitol or salicylate. The protection by antioxidants implies that the accelerated death of basal outer hair cells is due to free-radical damage. The results support an intrinsic susceptibility to free radicals that differs among cochlear cell populations. This differential provides a rational explanation for base-to-apex gradients observed in various forms of cochlear pathology.

Differential protective effects of neurotrophins in the attenuation of noise-induced hair cell loss.

The protective efficacy of neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) at 1 or 10 microg/ml was assessed in guinea pigs exposed to 4 kHz octave band noise at 115 dB SPL for 5 h. BDNF, NT-3 or artificial perilymph was delivered to the scala tympani via a mini-osmotic pump, beginning 4 days prior to noise exposure and continuing for 1 week post-exposure. Protection was assessed physiologically by the change in auditory brainstem response (ABR) threshold, and histologically by outer hair cell (OHC) survival. There was a statistically significant increase in OHC survival and a decrease in ABR threshold shift in animals receiving NT-3 at a concentration of 10 microg/ml. In animals receiving 1 microg/ml NT-3, there was a significant increase in OHC survival in the first row of OHC, but no significant change in ABR threshold, relative to control animals. In animals treated with BDNF, no significant functional or histological protection was observed. The protection afforded by NT-3 (10 microg/ml) treatment was similar in magnitude to that reported previously with glial cell line-derived neurotrophic factor and suggests that several factors may be involved in the protective response.

Influence of pulsed laser irradiation on the morphology and function of the guinea pig cochlea.

Recent experimental and clinical studies have demonstrated that several pulsed laser systems are also suitable for stapedotomy. The aim of the study was to investigate morphological and functional inner ear changes after irradiating the basal turn of the guinea pig cochlea with two pulsed laser systems of different wavelengths. The Er:YSGG (lambda=2.78 mcm) and Ho:YAG (lambda=2.1 mcm) lasers were used applying the laser energies necessary for perforating a human stapes footplate. The cochleas were removed 90 min, 1 day, 2 weeks, or 4 weeks after laser application. Acoustic evoked potentials (compound action potentials) were measured before and after laser application and at the above times immediately before removal of the cochleas. The organ of Corti was examined by scanning electron microscopy. Application of Er:YSGG laser parameters effective for stapedotomy had no adverse effects on Corti's organ in the guinea pig cochlea. On the other hand, effective Ho:YAG laser parameters cause damage to the outer hair cells with fusion of stereocilia and formation of giant cilia leading to partial or total cell loss. The inner hair cells and supporting cells were usually normal. These morphological data show a good correlation with the electrophysiological measurements. Our results clearly demonstrate that, besides achieving efficient bone management, the Er:YSGG laser has high application safety. On the other hand, the Ho:YAG laser is not well tolerated in our animal study. Its use in stapedotomy would be unreliable and dangerous for the inner ear.

Combined effects of noise and styrene exposure on hearing function in the rat.

Combined exposure to both noise and aromatic solvents such as styrene is common in many industries. In order to study the combined effects of simultaneous exposure to both noise and styrene on hearing, male adult Long-Evans rats were exposed either to 750 ppm styrene alone, to a 97 dB SPL octave band of noise centered at 8 kHz, or to a combination of noise and styrene. The exposure duration was 6 h/day, 5 days/week, for 4 consecutive weeks. Auditory function was tested over a frequency range from 2 to 32 kHz by recording near field potentials from the inferior colliculus, whereas histopathological analyses of the cochleae were performed with conventional morphometric approaches. Whereas both noise and styrene each caused permanent threshold shifts, the mechanisms of cochlear damage were different. Noise-induced hearing loss was mainly related to injuries of the stereocilia, whereas styrene-induced hearing loss was related to outer hair cell losses. Following the combined exposure, the threshold elevations as well as the cell losses exceeded the summed loss caused by noise and by styrene alone in the range of 8-16 kHz. Therefore, these results suggest that the two ototoxicants can cause a permanent synergistic loss of auditory sensitivity.

Sound-induced priming of the chinchilla auditory system.

Exposure of the auditory system to either continuous or interrupted nontraumatic noises, often collectively referred to as priming exposures, has been shown, in a number of experimental paradigms, to reduce the susceptibility of the auditory system to noise-induced hearing and sensory cell loss from a subsequent traumatic exposure. Using auditory evoked potentials to obtain pure-tone thresholds and cochleograms to quantify sensory cell losses, the issue of priming-induced protective effects was examined in the chinchilla. Priming was accomplished with either a continuous noise or with a continuous noise followed by an interrupted noise. Trauma was induced by exposure to high-level impacts over a 5-day period that resulted in an asymptotic threshold shift. A comparison of the two groups of primed subjects with an unprimed control group showed that there were some statistically significant reductions in the asymptotic response of the primed groups to the traumatic exposure but no differences in permanent changes in thresholds among the three groups 30 days following the traumatic exposure. There were, however, some statistically significant, frequency-specific, reductions in outer hair cell loss in the primed groups. When conditioning was followed by the interrupted exposure that produced a threshold shift toughening effect, the conditioning protocol had no effect on the response of subjects to the interrupted exposure. There were also no differences in thresholds or sensory cell loss between the two primed groups 30 days post-trauma. Priming protocols may have different effects on the development of noise-induced trauma that are dependent on the nature of the traumatic stimulus, that is, long-term high-level impact noise exposure versus acute continuous noise exposure.

Changes in distortion product otoacoustic emissions during prolonged noise exposure.

The aim of this study was to evaluate the reduction in 2f1-f2 distortion product otoacoustic emission (DPOAE) amplitude resulting from prolonged noise exposures. A group of five chinchillas was exposed continuously to an octave-band noise centered at 4.0 kHz for a total of 42 days, 6 days at each of seven exposure levels. Exposure level increased in 8-dB steps from 48 to 96 dB SPL. DPOAE input-output (I/O) functions were measured at octave intervals over a range of primary tone f2 frequencies between 1.2 and 9.6 kHz. Measurements were obtained (1) pre-exposure, (2) during days 3-6 of each 6-day exposure, and (3) 4 weeks after the final exposure. Continuous noise exposure caused a reduction in DPOAE amplitude that was greatest at f2 frequencies within and above (3.4-6.8 kHz) the octave-band noise exposure. For these f2 frequencies, DPOAE amplitudes decreased as exposure level increased up to approximately 72-80 dB SPL; higher exposure levels failed to cause any further reduction in DPOAE amplitude. The noise level at which DPOAE amplitude began to decrease was approximately 50 dB SPL. Above this critical level, DPOAE amplitude decreased 1.3 dB for every dB increase in noise level up to approximately 75 dB SPL.

Effects of bilateral olivocochlear lesions on vowel formant discrimination in cats.

Operant conditioning procedures were used to measure the effects of bilateral olivocochlear lesions on the cat's discrimination thresholds for changes in the second formant frequency (deltaF2) of the vowel /epsilon/. Three cats were tested with the formant discrimination task under quiet conditions and in the presence of continuous broadband noise at signal-to-noise ratios (S/Ns) of 23, 13, and 3 dB. In quiet, vowel levels of 50 and 70 dB produced average deltaF2s of 42 and 47 Hz, respectively, and these thresholds did not change significantly in low levels of background noise (S/Ns = 23 and 13 dB). Average deltaF2s increased to 94 and 97 Hz for vowel levels of 50 and 70 dB in the loudest level of background noise (S/N = 3 dB). Average deltaF2 thresholds in quiet and in lower noise levels were only slightly affected when the olivocochlear bundle was lesioned by making bilateral cuts into the floor of the IVth ventricle. In contrast, post-lesion deltaF2 thresholds in the highest noise level were significantly larger than pre-lesion values; the most severely affected subject showed post-lesion discrimination thresholds well over 200 Hz for both 50 and 70 dB vowels. These results suggest that olivocochlear feedback may enhance speech processing in high levels of ambient noise.