Functional and morphological response of the stria vascularis following a sensorineural hearing loss

Cochlear endolymph is maintained at a potential of (+)80 mV by an active transport mechanism involving the stria vascularis (SV). This so-called endocochlear potential (EP) is integral to hair cell transduction. We compared the EP with changes in SV area and Na(+),K(+)-ATPase expression following a sensorineural hearing loss. Guinea pigs were deafened using kanamycin and a loop diuretic, and the EP was measured at two, 14, 56, 112 or 224 days following deafening. Auditory brainstem responses were used to confirm that each animal had a severe-profound hearing loss. There was a significant reduction in EP following two days of deafness (normal, 73.5 mV S.E.M.=2.4; deaf, 42.1 mV, S.E.M.=2.8; P<0.0001, t-test). In animals deafened for 14 days the EP had partially recovered (65.2 mV, S.E.M.=5.08), while animals deafened for longer periods exhibited a complete recovery (56 days 80.5 mV, S.E.M.=5.36; 112 days 75.7 mV, S.E.M.=2.71; 224 days 81.0 mV; S.E.M.=6.0). Despite this recovery, there was a systematic reduction in SV area with duration of deafness over the first 112 days of deafness. Significant reductions were localised to the basal turn in animals deafened for two days, but had extended to all turns in animals deafened for 112 days. While there was a significant reduction in strial area, the optical density of Na(+),K(+)-ATPase within the remaining SV was normal. Since the treated animals exhibited essentially a complete elimination of all hair cells, the total K(+) leakage current from the scala media would be expected to be significantly reduced. The large reduction in the extent of the SV after deafening suggests that a reduced strial volume is capable of maintaining a normal EP under conditions of reduced K(+) leakage current.     

Long-term changes in off-lesion endocochlear potential after induction of localized lesions in the lateral wall

Localized lesions were produced in various turns of the guinea pig cochlea by means of a photochemical reaction between systemically administered rose bengal dye and green light illumination. The endocochlear potential (EP) was measured at various off-lesion sites, and a morphological examination was performed. In a previous study, this same investigation was done at 3 days, at which time all sites apical to the lesion showed significant EP depression, and damage to the stria vascularis at the lesion was ongoing. In the present 2-week study, the apical EP values were not different from the basal values, and all experimental values were essentially the same as the EP values found in control animals. Morphological examination revealed that the previously damaged structures were greatly repaired. Localized damage and early apical EP depression followed by damage repair and eventual EP recovery could account for the clinical course of certain cases of idiopathic sudden hearing loss involving low-tone deafness.     

Cisplatin-induced ototoxicity: morphological evidence of spontaneous outer hair cell recovery in albino guinea pigs?

Cisplatin is frequently used in the treatment of various forms of malignancies. Its therapeutic efficacy, however, is limited by the occurrence of sensorineural hearing loss. Little is known about the course of hearing loss over longer time intervals after cessation of cisplatin administration. Infrequently, recovery of hearing has been described in animals and humans. Stengs et al. (1997) treated guinea pigs with cisplatin at a daily dose of 1.5 mg/kg for 8 consecutive days and subsequently studied cochlear function after survival times varying from 1 day to 16 weeks. Spontaneous improvement of the hair cell-related potentials (cochlear microphonics and summating potentials) was observed starting 2 weeks after cessation of treatment. In the present study we examined light microscopically the cochleas used in the study of Stengs et al. (1997). One day after cessation of cisplatin administration outer hair cell (OHC) loss in the basal cochlear turn averaged 66%. In the 1-week survival group, OHC counts were similar to those of the 1-day survival group. In the 4-week survival group, however, a relatively small loss of OHCs was found in the basal cochlear turn; OHC loss averaged only 15%. A similar loss was found after 8 weeks. In the 16-week survival group, OHC loss in the basal turn increased to 48%, but this was not statistically significant. Our histological observations are in line with the electrophysiological data from the same animals. Our findings suggest that OHCs recover from cisplatin-induced damage 1-4 weeks after treatment. However, the results do not allow a conclusion as to whether the observed recovery is due to the formation of new OHCs or to (self-)repair of damaged OHCs.     

Thyroid hormone is not necessary for the development of outer hair cell electromotility

The outer hair cell (OHC), one of two receptor cell types in the organ of Corti, plays a critical role in mammalian hearing. OHCs enhance basilar membrane motion through a local mechanical feedback process within the cochlea, termed the 'cochlear amplifier'. It is generally believed that the basis of cochlear amplification is a voltage-dependent electromotile response of OHCs. Measurements of electromotility in developing animals indicate that the onset of motility normally occurs around 7 days after birth in altricial rodents such as gerbils and rats. Thyroid hormone (TH) plays a crucial role in the development of the auditory system. Deficiency of the hormone between the late embryonic stage and the second postnatal week can cause severe hearing loss. Several studies suggest that TH deficiency might also affect the development of the cochlear amplifier. The goal of this study was therefore to examine whether TH was necessary for the development of OHC motility. The organ of Corti of gerbils was dissected out at birth and grown in culture with defined concentration of triiodothyronine (T3), the active ligand for the TH receptor. Motility was measured from OHCs isolated from 7-, 11- and 14-day-old cultures. Motility did indeed develop in OHCs deprived of normal concentration of T3. This suggests that the defective auditory function seen in TH-deficient animals is most likely due to morphological and physiological changes in the cochlea, rather than the motor function of the OHCs.     

Degeneration in the cochlea after noise damage: primary versus secondary events

PURPOSE: To determine if noise damage in the organ of Corti is different in the low- and high-frequency regions of the cochlea. MATERIALS AND METHODS: Chinchillas were exposed for 2 to 432 days to a 0.5 (low-frequency) or 4 kHz (high-frequency) octave band of noise at 47 to 95 dB sound pressure level. Auditory thresholds were determined before, during, and after the noise exposure. The cochleas were examined microscopically as plastic-embedded flat preparations. Missing cells were counted, and the sequence of degeneration was determined as a function of recovery time (0-30 days). RESULTS: With high-frequency noise, primary damage began as small focal losses of outer hair cells in the 4-8 kHz region. With continued exposure, damage progressed to involve loss of an entire segment of the organ of Corti, along with adjacent myelinated nerve fibers. Much of the latter loss is secondary to the intermixing of cochlear fluids through the damaged reticular lamina. With low-frequency noise, primary damage appeared as outer hair cell loss scattered over a broad area in the apex. With continued exposure, additional apical outer hair cells degenerated, while supporting cells, inner hair cells, and nerve fibers remained intact. Continued exposure to low-frequency noise also resulted in focal lesions in the basal cochlea that were indistinguishable from those resulting from exposure to high-frequency noise. CONCLUSIONS: The patterns of cochlear damage and their relation to functional measures of hearing in noise-exposed chinchillas are similar to those seen in noise-exposed humans. Thus, the chinchilla is an excellent model for studying noise effects, with the long-term goal of identifying ways to limit noise-induced hearing loss in humans.     

Survival of Neural Stem Cells in the Cochlea

Adult rat hippocampus-derived neural stem cells (NSCs) have been reported to have been successfully grafted in several brain regions. To evaluate the possibility of treatment of sensorineural hearing loss using NSCs, survival of NSCs in the cochlea was estimated. NSCs were grafted into newborn rat cochleas. Within 2-4 weeks of grafting to the cochlea, some NSCs survived in the cochlear cavity. Some of them had adopted the morphologies and positions of hair cells. This suggests that NSCs can adapt to the environment of the cochlea and gives hope for treatment of the damaged cochlea and sensorineural hearing loss.     

Survival of neural stem cells in the cochlea

Adult rat hippocampus-derived neural stem cells (NSCs) have been reported to have been successfully grafted in several brain regions. To evaluate the possibility of treatment of sensorineural hearing loss using NSCs, survival of NSCs in the cochlea was estimated. NSCs were grafted into newborn rat cochleas. Within 2-4 weeks of grafting to the cochlea, some NSCs survived in the cochlear cavity. Some of them had adopted the morphologies and positions of hair cells. This suggests that NSCs can adapt to the environment of the cochlea and gives hope for treatment of the damaged cochlea and sensorineural hearing loss.     

Effects of age on the distortion product otoacoustic emission growth functions.

Age-related hearing loss (presbycusis) is thought to result from age-related degeneration (aging) of the cochlea plus the cumulative effects of extrinsic damage (noise and other ototoxic agents) and intrinsic disorders (e.g. systemic diseases). Previous studies have implicated dysfunction of the hair cells (sensory presbycusis) as the principal mechanism of age-related hearing loss. However, recent evidence from quiet-reared gerbils suggests that cochlear aging results primarily from atrophy of the stria vascularis, which is associated with diminished endocochlear potential (EP), spiral ganglion atrophy, and a relatively flat audiometric loss, termed metabolic presbycusis. Because it is not currently possible to measure EP directly in the clinical setting, we wondered if cochlear metabolic dysfunction might be evidenced indirectly from existing clinical tests, specifically, the input-output (IO) growth function of the distortion product (DP) otoacoustic emissions in relation to behavioral hearing threshold levels (HTL). We anticipated finding discordance between the IO functions and HTL with either a greater decline with age in HTL than in IO functions if an age-related metabolic dysfunction of the cochlea was operant, or a greater loss of IO function than HTL if outer hair cell dysfunction was the dominant pathology. To address this supposition we analyzed existing auditory data from a large cohort of adults to determine the change with age in three aspects of the DP IO function: area under the curve, threshold, and slope. The analyses demonstrated a greater effect of age on HTL than on the DP IO measures. This effect supports the hypothesis that strial dysfunction is a substantive factor in cochlear aging. The etiology and mechanisms for this dysfunction are conjectural at present.     

Pathological alterations of strial capillaries in dominant white spotting W/Wv mice

Dominant white spotting W/W(v) and W(v)/W(v) mice are well-known mutants that lack strial intermediate cells in their cochlea and manifest hereditary sensorineural hearing loss. We recently reported marked thickening of and IgG deposition on the basement membrane of strial capillaries in W/W(v) mutant mice, similar to observations made in aged animals and in animals with autoimmune sensorineural hearing loss. The present study aimed to clarify the age-dependent changes in these pathological findings of strial capillaries in the W/W(v) mice. Male WBB6F1 +/+ and dominant white spotting W/W(v) mutant mice were sacrificed by transcardiac perfusion with paraformaldehyde solution. The cochlear ducts were isolated and subjected to light- and electron-microscopy, immunohistochemistry, immunoelectron microscopy. Alternatively, lanthanum chloride tracer examination in the isolated cochlear ducts was performed in order to compare the permeability of the strial capillaries between +/+ and W/W(v) mice. In the W/W(v) mice, thickening of and IgG deposition on the basement membrane of strial capillaries were observed as early as 1 week after birth and became more noticeable with age. Deposited IgG was preferentially localized to the thickened basement membrane and was also observed in partially the intercellular space between adjacent of endothelial cells. In addition, pinocytotic vesicles both in the apical and basal lesions of such cells also showed IgG deposition. Lanthanum chloride was retained along apical plasma membrane of the endothelial cells in the +/+ mice but penetrated through the endothelial layer in the W/W(v) mice. These results indicate that active transport via pinocytotic vesicles as well as increased permeability of strial capillaries in the W/W(v) mice occur in the early stage after birth, resulting in the morphological alterations in the strial capillaries of these mice.     

Hidden cochlear impairments

Pure tone audiometry is a routine clinical examination used to identify hearing loss. A normal pure tone audiogram is usually taken as evidence of normal hearing. Auditory deficits detected in subjects with normal audiograms, such as poor sound discrimination and auditory perceptual disorders, are generally attributed to central problems. Does the pure tone audiogram truly reflect cochlear status? Recent evidence suggests that individuals with normal audiogram may still have reduced peripheral auditory responses but normal central responses, indicating that the pure tone audiometry may not detect some types of cochlear injuries. In the cochlea, the outer hair cells (OHCs), inner hair cells (IHCs), and the spiral ganglion neurons that synapse with IHCs are the 3 key cochlear components in transducing acoustical vibrations into the neural signals. This report reviews three types of cochlear damage identified in laboratory animals that may not lead to overt hearing loss. The first type of cochlear impairment, such as missing a certain proportion of IHCs without damage to OHCs, may reduce the cochlear output and elevate response threshold; however, the reduced peripheral auditory sensitivity may be restored along the auditory pathway via central gain enhancement. The second type of cochlear impairment, such as selective damage to the synapses of the high-threshold thin auditory nerve fibers (ANFs), reduces cochlear output at high stimulation levels with no effect on response threshold. In this case the reduced cochlear output may be compensated along the auditory pathway as well. The third type of cochlear impairment, such as missing a certain number of OHCs without damage to others, may not even affect cochlear function at all. These “hidden” cochlear impairments do not result in overt hearing loss, but they may increase the vulnerability of the cochlea to traumatic exposure and lead to disrupted central auditory processing.     

Cytotoxic changes in hair cells secondary to pneumococcal middle-ear infection

To determine whether the bacterial toxins associated with otitis media could induce morphologic changes in the organ of Corti, we inoculated the middle-ear cavities of healthy guinea pigs with either Streptococcus pneumoniae or sterile saline and then examined the organ of Corti histologically at 1, 2, and 3 weeks postinoculation. We found that the outer hair cells (OHCs) in the infected ears underwent several changes that were dependent on both the length of time following inoculation and also the position of the OHCs in the cochlea. At 2 weeks postinoculation, 7.0 to 20% of the OHC nuclei from the infected animals became very swollen, with the most significant swelling occurring in the basal turn. At 3 weeks postinoculation, 2.5 to 3.5% of the OHCs were missing in the infected animals, with the most significant loss occurring in the basal and middle turns. These results suggest that bacterial otitis media can produce cytotoxic changes in the cochlea. These changes may be a clinically significant factor in the temporary and permanent sensorineural hearing loss that has been associated with bacterial otitis media.     

均衡噪声阈值检测法研究耳蜗死区在感音神经性聋患者耳蜗中的分布

目的探讨在感音神经性聋患者中是否存在耳蜗死区及其分布情况。方法采用均衡噪声阈值检测法检测82例(130耳)感音神经性聋患者和25例(50耳)正常听力者是否存在耳蜗死区,并比较耳蜗死区与性别、年龄、耳别、听力损失程度以及病程的关系。结果 82例感音神经性聋患者中有41.46%(34/82)存在耳蜗死区,正常听力者中无耳蜗死区,两者差异具有统计学意义(P<0.01)。耳蜗死区的存在在性别、年龄和耳别之间无明显差异,而不同听力损失程度、病程的感音神经性聋患者耳蜗死区的检出率差异有统计学意义(P<0.05),听力损失越重,病程越长,检出率越高。33.85%(44/130)受试耳存在耳蜗死区,其中高频区耳蜗存在死区者占23.08%(30/130),低频区耳蜗存在死区者占2.31%(3/130),高低频区同时存在耳蜗死区者占8.46%(11/130),高频耳蜗死区检出率远高于低频区。结论在感音神经性聋患者存在耳蜗死区中,耳蜗死区的存在与听力损失程度及病程有关,听力损失程度越重、听力受损时间越长,存在耳蜗死区的可能性越大。     

Acute hearing loss in patients with hematological disorders

Objective: This study adopted an inner ear test battery to investigate the causes of acute sensorineural hearing loss in patients with hematological disorders. Methods: During the past 20 years, the authors have experienced 14 patients with hematological disorders, i.e. leukemia or aplastic anemia, having acute sensorineural hearing loss. An inner ear test battery comprising audiometry and cervical vestibular-evoked myogenic potential (cVEMP), ocular VEMP (oVEMP), and caloric tests was performed. Results: Diagnoses comprised of sudden sensorineural hearing loss in 12 patients and endolymphatic hydrops in four patients (two patients had one ear with sudden sensorineural hearing loss while the other ear had endolymphatic hydrops). Percentages of recruitment phenomenon showed a significant difference between endolymphatic hydrops and sudden sensorineural hearing loss. Abnormal percentages for mean hearing level (86%), cVEMP test (71%), oVEMP test (25%), and caloric test (14%) exhibited a significant sequential decline in these patients. Conclusion: Acute sensorineural hearing loss in a patient with leukemia or aplastic anemia may be related to either sudden sensorineural hearing loss or endolymphatic hydrops. A significant sequential decline in the function of the cochlea, saccule, utricle, and semicircular canals indicates that the pars inferior is more vulnerable to blood insult than the pars superior.     

Determining the cause of hearing loss: differential diagnosis using a comparison of audiometric and otoacoustic emission responses

OBJECTIVE: The purpose of this study was to further investigate the possibility of developing noninvasive methods of differential diagnosis of hearing disorders through the study of experimental animals with induced lesions. In particular, it was desired to compare distortion product otoacoustic emission (DPOAE) responses and auditory brain stem response (ABR) thresholds in Mongolian gerbils having either acoustic or strial damage, using as a reference the same responses measured in a control group of normal young adult gerbils. The goal was to evaluate the potential clinical application of this approach to determining the dominant contribution to sensorineural hearing loss in individual human subjects. DESIGN: DPOAE input-output functions and ABR thresholds were measured over a wide range of stimulus frequencies for three groups: (1) a reference group of normal young adult gerbils; (2) a group in which acoustic damage had been induced 2 wk earlier; (3) a group in which damage to the stria vascularis was induced by a series of furosemide injections. The responses in the experimental groups relative to the normal means were compared to determine which combinations of responses were effective in discriminating between animals with different lesions. Three measures were evaluated in detail: the ABR threshold, the emission threshold at a criterion emission amplitude, and the emission amplitude at a high stimulus level. RESULTS: Considering cases with significant hearing loss (ABR thresholds elevated by 20 dB or more), the best method for distinguishing between the two lesions involved a two-dimensional plot comparing emission and ABR thresholds at the same stimulus frequencies. Acoustic damage cases were found in a broad region where the emission and ABR thresholds were roughly equal, whereas strial damage cases were found in a narrower region where the emission threshold was about 0.4 times the ABR threshold (both in dB). These two cases were compared with a third case introduced by definition, that is, damage to inner hair cell or neural systems resulting in an increase in audiometric threshold but no change in emission responses (e.g., auditory neuropathy). The responses for these three cases were found to lie in different regions of the two-dimensional plot comparing emission and ABR thresholds, provided only that ABR thresholds were elevated 20 dB or more. This diagram also revealed cases of preclinical acoustic damage, in which the ABR threshold was shifted less than 20 dB but where the emission threshold was significantly elevated. CONCLUSIONS: The results clearly demonstrate the possibility of developing a clinical method of noninvasive differential diagnosis of hearing loss. The method demonstrated was to add to a standard audiometric evaluation the measurement of DPOAE growth functions over the range of frequencies where these emissions were relatively easy to measure and consistent. The DPOAE stimulus frequencies were chosen to match the audiometric frequencies, and the corresponding emission and audiometric thresholds were compared on a threshold-threshold plot for each individual at a number of stimulus frequencies. Responses in different regions in this plot were found to correspond to different types of sensorineural hearing loss.     

Effect of impulse noise exposure on the endocochlear potentials]

Effects of impulse noise exposure (25 impulses, peak level 165 dB SPL) on endocochlear potentials (EP) and CAP threshold were investigated in guinea pigs. Eight hours after exposure, EP recorded from the second turn of the cochlea was very low (19.0 +/- 1.7 mV) and the negative EP resulted from prolonged anoxia was markedly diminished (-EPmax = -6.4 +/- 1.3 mV). The return rate of EP after reventilation was also reduced. The positive EP returned to normal values 7 days after exposure but the negative EP and the CAP threshold did not. The results suggest that the stria vascularis was also damaged together with the organ of Corti, the degree of damage seemed to be heavier in the latter if only complete recovery of positive EP is taken into consideration. The stria vascularis was also not completely restored when examining the return rate of EP after reventilation. Mechanisms underlying the changes in EP and hearing sensitivity after noise exposure are discussed.     

Effect of perilymphatic air perfusion on cochlear potentials

Perilymphatic fistula is now widely recognized to cause acute profound hearing loss. It is still controversial, however, which mechanism it is that causes the reversible hearing loss. Recently, it has been suggested by two groups of researchers that the intrusion of air bubbles into the perilymphatic space (a condition called pneumolabyrinth or aerolabyrinth) through the ruptured labyrinthine window(s) may be one of the causes. In order to examine the mechanism underlying the hearing loss associated with pneumolabyrinth, the perilymphatic space of the guinea pig cochlea was perfused with air and cochlear potentials were recorded. Although perfusion of the scala tympani with air at a rate as high as 200 microliter/min caused an immediate and drastic decrease of the cochlear microphonics (CM) and the compound action potential (AP), it had little effect on the endocochlear dc potential (EP) during perfusion for 20 min. A decline in EP was seen in half the ears, but only when the duration of perfusion exceeded 30 min. These results show that the EP has an amazing resistance to air trapped in the scala tympani of the cochlea and that the initial decrease of hearing acuity after the elimination of perilymph from the scala tympani (or introduction of air into the scala tympani) is probably due to interference in CM and AP generation mechanisms rather than to strial dysfunction.     

Effects of industrial noise exposure on distortion product otoacoustic emissions (DPOAEs) and hair cell loss of the cochlea--long term experiments in awake guinea pigs

Distortion product otoacoustic emissions (DPOAEs), a sensitive detector of outer hair cell (OHC) function, cochlear microphonics (CM), and hair cell loss have been monitored in 12 awake guinea pigs before and after 2 h exposure to specific, played-back industrial noise (105 dB SPL maximal intensity). All animals had stable DPOAE levels before noise exposure. In the first hours after noise exposure DPOAE levels were reduced significantly. In about 70% a partial recovery of the DPOAEs was found within 4 months after noise exposure. In 16% of the investigated ears no recovery of DPOAEs was observed. However, in a few ears increased DPOAEs were observed after noise exposure. Exposure to industrial noise caused both morphological changes in the middle turns of the cochlea and electrophysiological changes in the middle frequency range. A close correlation existed between reduced DPOAE levels, loss in CM potentials, and area of damaged or lost OHCs, but not with the numbers of damaged or lost OHCs in the cochlea. It can be concluded that continuous industrial noise causes a damage to OHCs which differs form the damage caused by impulse noise.     

Effects of profound sensorineural loss on gerbilline auditory encephalopathy

To investigate the role of acoustic stimulation in the development of spongiform degeneration in the cochlear nuclei of Mongolian gerbils, the right cochlea in 8 juvenile gerbils was chemically treated by placing sodium chloride (NaCl) crystals on the cochlear round window membrane. Sixty days after NaCl treatment there was extensive damage to the strial, sensorineural and supporting cells of the treated inner ear. The cochlear damage was accompanied by a dramatic decrease in the number and the extent of the spongioid lesions in the ipsilateral cochlear nuclei compared to the contralateral (control) cochlear nuclei. These results lend further support to the hypothesis that the progress of this disorder is related to auditory function.     

Strial microvascular pathology and age-associated endocochlear potential decline in NOD congenic mice

NOD/ShiLtJ (previously NOD/LtJ) inbred mice show polygenic autoimmune disease and are commonly used to model autoimmune-related type I diabetes, as well as Sjogren's syndrome. They also show rapidly progressing hearing loss, partly due to the combined effects of Cdh23ahl and Ahl2. Congenic NOD.NON-H2nb1/LtJ mice, which carry corrective alleles within the H2 histocompatibility gene complex, are free from diabetes and other overt signs of autoimmune disease, but still exhibit rapidly progressive hearing loss. Here we show that cochlear pathology in these congenics broadly includes hair cell and neuronal loss, plus endocochlear potential (EP) decline from initially normal values after two months of age. The EP reduction follows often dramatic degeneration of capillaries in stria vascularis, with resulting strial degeneration. The cochlear modiolus also features perivascular inclusions that resemble those in some mouse autoimmune models. We posit that cochlear hair cell/neural and strial pathology arise independently. While sensory cell loss may be closely tied to Cdh23ahl and Ahl2, the strial microvascular pathology and modiolar anomalies we observe may arise from alleles on the NOD background related to immune function. Age-associated EP decline in NOD.NON-H2nb1 mice may model forms of strial age-related hearing loss caused principally by microvascular disease. The remarkable strial capillary loss in these mice may also be useful for studying the relation between strial vascular insufficiency and strial function.     

The effects of high-frequency hearing loss on low-frequency components of the click-evoked otoacoustic emission

Click-evoked otoacoustic emission (CEOAE) input/output (I/O) functions were measured in ears with normal hearing and in ears with sensorineural hearing loss above 2000 Hz. The low- to midfrequency CEOAEs obtained from the ears with high-frequency hearing loss were significantly reduced in level compared to the CEOAEs obtained from the ears with normal hearing even though there were no significant group differences in the 250-2000 Hz pure-tone thresholds. The findings are discussed within the context of two hypotheses that explain the low- to midfrequency reduction in transient-evoked otoacoustic emission (TEOAE) magnitude: (1) subclinical damage to the more apical regions of the cochlea not detected by behavioral audiometry, or (2) trauma to the basal region of the cochlea that affects the generation of low-frequency emissions. It is proposed that localized damage at basal cochlear sites affects the generation of low- to midfrequency CEOAE energy.