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Cochlear sensitivity in the lesser spear-nosed bat, Phyllostomus discolor.

Behavioral auditory thresholds of Phyllostomus discolor are characterized by two threshold minima separated by an insensitive region at about 55 kHz (Esser and Daucher 1996). To investigate whether these characteristics are due to cochlear properties, we recorded distortion product otoacoustic emissions (DPOAEs) and calculated relative DPOAE threshold curves, which proved to be a good measure of cochlear sensitivity. Our results indicate that in P. discolor, cochlear sensitivity, as assessed by DPOAE recordings, does not show a threshold maximum at 55 kHz. The DPOAE threshold curves display an absolute minimum at approximately 30 kHz, and from that frequency region, the threshold continuously increases without any pronounced irregularities. The frequency tuning properties of the cochlea, as assessed by DPOAE suppression tuning curves (STCs) reveal broad filter bandwidths with Q10dB values between 3.4 and 10.7. There are no frequency-specific specializations of cochlear tuning. The characteristic pattern of subsequent threshold maxima and minima at high frequencies observed in behavioral studies seems to be shaped by transfer characteristics of the outer ear and/or neuronal processing in the ascending auditory pathway rather than by cochlear mechanics.

Animals↗

Prepulse startle deficit in the Brown Norway rat: a potential genetic model.

Prepulse inhibition (PPI), an operational measure of sensorimotor gating, is deficient in schizophrenia patients. PPI was compared among 4 strains of rats: Sprague-Dawley, Spontaneously Hypertensive, Wistar Kyoto (WKY), and Brown Norway (BN). PPI was dramatically lower in BN versus the other strains, especially WKY, for both acoustic and airpuff startle stimuli, whereas startle amplitude was similar between BN and WKY. Female BN also had lower PPI than did female WKY. Response to increasing prepulse intensities showed a right shift in the BN relative to the WKY. Visual prepulses also showed deficiencies in BN versus WKY. The absence of background noise did not negate strain differences. Auditory brainstem response to clicks and tone pips revealed no differences in auditory threshold between the 2 strains. These results are the first to demonstrate that BN have impaired sensorimotor gating compared with WKY, without impaired acoustic acuity.

Animals↗

Prebycusis: physiological or pathological.

A study was made on human temporal bones to elucidate the effects of aging on the auditory system. Ninety-six ears from 68 individuals, varying in age from infancy to 84 years, served as 'normal ears'. None of these cases had clinical or pathological evidence of specific ear diseases. 'Pathological ears' consisted of 89 ears from 58 individuals which exhibited slowly progressive hearing loss, and which had no specific known cause for the loss. Two aging phenomena were found to affect the human ear. The first is physiological, and has been called 'auditory senility'. It involves all the different parts of the auditory mechanism equally, and is responsible for the rise in auditory thresholds for the high frequencies, commonly seen in elderly people. The second phenomenon is pathological, and was termed 'auditory decay'. It involves only the perceptive system of the ear, and results in different types of clinical presentations, according to the morphological layer involved. Therefore, the recognition of two aging phenomena which affect the human ear may explain the reason for the wide variations in auditory acuity associated with old age.

Adolescent↗

The first successful case of hearing produced by electrical stimulation of the human midbrain.

HYPOTHESIS: Electrical stimulation of the inferior colliculus in the midbrain can provide a safe and efficacious alternative to auditory brainstem implants (ABIs). BACKGROUND: Patients with neurofibromatosis type 2 (NF2) receive limited speech recognition with ABIs. Some ABI patients without NF2 can achieve excellent speech understanding, suggesting that the limited NF2 performance is due to brainstem damage from the tumor and its removal. METHODS: An array of electrodes (Med-El ABI) was placed on the dorsal surface of the inferior colliculus in the midbrain of a human volunteer as an auditory prosthesis via an infratentorial supracerebellar median surgical approach. Electrophysiological responses, psychophysical responses, and speech recognition were measured. RESULTS: Electrical stimulation produced auditory sensations on all 12 electrodes with no nonauditory sensations. Auditory threshold levels indicated the stability of the electrode array over time. Electrophysiological measures showed activation in the contralateral auditory cortex but none in ipsilateral cortex. All electrodes demonstrated a full range of loudness sensation and electrode-specific pitch sensations. Speech recognition was significant, but limited in the first month after surgery. CONCLUSION: This approach may provide advantages for patients with brainstem damage.

Adult↗

Auditory effect of kanamycin given to newborn guinea pigs whose mothers received kanamycin during pregnancy.

Clinical and experimental data indicate that aminoglycoside ototoxicity occurs more frequently in individuals previously exposed to ototoxic drugs. This study investigated the auditory effect of repetitive administration of kanamycin on newborn guinea pigs that had previously been exposed, in utero, to kanamycin administered to their mothers. Sixteen pregnant guinea pigs in the late stages of gestation were divided into two groups, one receiving kanamycin 500 mg/kg per day intramuscularly for 8 days, and the other acting as a control. After birth, the mothers and their newborns in both groups were examined for auditory brain stem response (ABR) and then treated with kanamycin 500mg/kg per day for 4 days. The results from the second examination demonstrated that the group receiving prior treatment with kanamycin, despite their good ABR responses during the first measurement, showed significantly elevated auditory thresholds compared to the control group. Therefore, any ototoxic drugs should be used with extreme caution in newborns having had prior exposure to the drugs in utero, even if they have a "normal" auditory response after birth.

Animals↗

[Evaluation of the possible ototoxicity of josamycin by high frequency audiometry].

Josamycin is an antibiotic macrolide similar to erythromycin, with some differences in its biologic behaviour. There have been no reports of ototoxic effects caused by this drug, but its similitudes with erythromycin have prompted us to undertake a study about its possible cochleo-toxicity. Most trials of this kind have been carried out using conventional audiometry (up to 8,000 Hz), thus not being able to detect threshold shifts above this frequency. Ototoxic lesions usually begin in the upper frequency limit. Twenty-eight patients without previous auditory impairment were studied with conventional (up to 8,000 Hz) and high-frequency audiometry (up to 20,000 Hz) before and after oral treatment with josamycin during eight days. No significant differences were found in auditory thresholds registered before and after treatment in any of the patients. These results suggest that josamycin is devoid of any cochleo-toxic effect in all the frequencies that a normal subject can hear.

Adult↗

Effects of listener sophistication on respiration audiometry.

Thirty normal-hearing college-age adults were tested by standard and respiration audiometry (RA) at 1000 Hz to investigate the effects of subject knowledge of the RA procedure. Three levels of sophistication were employed: (1) no knowledge, (2) full knowledge, and (3) deception. No significant effects on RA thresholds were revealed as a function of subject knowledge. RA itself was found to be less satisfactory as a means of measuring auditory threshold because of the difficulty in obtaining responses from some subjects and the degree of subjectivity required to judge responses.

Audiometry↗

NF-kappaB mediated glucocorticoid response in the inner ear after acoustic trauma.

The inner ear of humans and experimental animals demonstrate an abundance of glucocorticoid receptors (GR). Glucocorticoids (GC) are widely used to treat different hearing disorders; yet the mechanisms of GC action on the inner ear are unknown. We demonstrate how GR can directly modulate hearing sensitivity in response to a moderate acoustic trauma that results in a hearing loss (10-30 dB). The GC agonist (dexamethasone) and the drugs (metyrapone + RU 486) showed opposing effects on hearing threshold shifts. GC agonist (dexamethasone) decreased the hearing threshold whereas pre-treatment with a GC synthesis inhibitor (metyrapone) in combination with a GR antagonist (RU 486) exacerbated auditory threshold shifts (25-60 dB) after acoustic trauma with statistically significant increase in GR mRNA and GR protein compared with the vehicle and acoustic trauma group. Acoustic trauma caused a significant increase in the nuclear transport of NF-kappaB, whereas pre-treatment with the drugs (metyrapone and RU 486) blocked NF-kappaB nuclear transport into spiral ganglion nuclei. An NF-kappaB inhibitor, pyrrolidine dithiocarbamate ammonium blocked the trauma-induced translocation of NF-kappaB and resulted in a hearing loss (45-60) dB. These results indicate that several factors define the responsiveness of the inner ear to GC, including the availability of ligand or receptor, and the nuclear translocation of GR and NF-kappaB. These findings will further our understanding of individual GC responsiveness to steroid treatment, and will help improve the development of pharmaceuticals to selectively target GR in the inner ear for individuals with increased sensitivity to acoustic trauma.

Acoustic Stimulation↗

Recovery of structure and function of inner ear afferent synapses following kainic acid excitotoxicity.

The present study was conducted to examine the re-establishment of IHC/VIII nerve synapses following kainic acid (KA) excitotoxicity and to discern if the re-organized afferent could render not only a normal auditory threshold but also a normal supra-threshold function. KA (60 mM) applied to the intact round window membrane in chinchilla destroyed postsynaptic endings of the auditory nerve, depressed the input-output (I/O) functions of auditory evoked potentials (EVP) and produced an average loss of sensitivity of over 80 dB at 4, 8, and 16 kHz, with less substantial losses (40-60 dB) at lower frequencies. However, there was no significant difference in 2f1-f2 distortion-product otoacoustic emissions (DPOAE) before and after the application of KA. The nerve endings went through a sequence of swelling, degeneration and recovery over a 3-5 day period at higher frequency. Auditory sensitivity and supra-threshold response returned accordingly. In contrast, complete recovery at lower frequencies (1 and 2 kHz) required more than 5 days. The results provide strong evidence that (1) excitotoxically damaged cochlear afferent neurons can recover and render both a normal EVP threshold and EVP I/O function and (2) afferent innervation to IHCs is not necessary for DPOAE generation.

Animals↗

Glutathione limits noise-induced hearing loss.

The generation of reactive oxygen species (ROS) is thought to be part of the mechanism underlying noise-induced hearing loss (NIHL). Glutathione (GSH) is an important cellular antioxidant that limits cell damage by ROS. In this study, we investigated the effectiveness of a GSH supplement to protect GSH-deficient animals from NIHL. Pigmented guinea pigs were exposed to a 4 kHz octave band noise, 115 dB SPL, for 5 h. Group 1 had a normal diet, while groups 2, 3 and 4 were fed a 7% low protein diet (leading to lowered tissue levels of GSH) for 10 days prior to noise exposure. One hour before, immediately after and 5 h after noise exposure, subjects received either an intraperitoneal injection of 5 ml/kg body weight of 0.9% NaCl (groups 1 and 2), 0.4 M glutathione monoethyl ester (GSHE; group 3) or 0.8 M GSHE (group 4). Auditory thresholds were measured by evoked brain stem response at 2, 4, 8, 12, 16 and 20 kHz before and after noise exposure. Ten days post exposure, group 1 showed noise-induced threshold shifts of approximately 20 dB at 2, 16 and 20 kHz and 35 to 40 dB at other frequencies. Threshold shifts in group 2 were significantly greater than baseline at 2, 4, 16 and 20 kHz. GSHE supplementation in a dose-dependent fashion attenuated the threshold shifts in the low protein diet animals. Hair cell loss, as evaluated with cytocochleograms, was consistent with the auditory-evoked brainstem response results. Group 2 exhibited significantly more hair cell loss than any of the other groups; hair cell loss in group 3 was similar to that seen in group 1; group 4 showed less loss than group 1. These results indicate that GSH is a significant factor in limiting noise-induced cochlear damage. This is compatible with the notion that ROS generation plays a role in NIHL and that antioxidant treatment may be an effective prophylactic intervention.

Animals↗

Ototoxicity of the three xylene isomers in the rat.

Numerous experiments have shown that the aromatic solvents can affect the auditory system in the rat, the cochlea being targeted first. Solvents differ in cochleotoxic potency: for example, styrene is more ototoxic than toluene or xylenes. The goal of this study was to determine the relative ototoxicity of the three isomers of xylene (o-, m- or p-xylene). Moreover, by dosing with the two urinary metabolites of xylene, methylhippuric (MHAs) and mercapturic acids (MBAs), this study points toward a causal relationship between the cochleotoxic effects and potential reactive intermediates arising from the biotransformation of the parent molecules. Separate groups of rats were exposed by inhalation to one isomer following this schedule: 1800 ppm, 6 h/d, 5 d/wk for 3 wk. Auditory thresholds were determined with brainstem-auditory evoked potentials. Morphological analysis of the organ of Corti was performed by counting both sensory and spiral ganglion cells. Among the three isomers, only p-xylene was cochleotoxic. A 39-dB permanent threshold shift was obtained over the tested frequencies range from 8 to 20 kHz. Whereas outer hair cells were largely injured, no significant morphological change was observed within spiral ganglia. The concentrations of urinary p-, o- or m-MHA were greater (p-MHA: 33.2 g/g; o-MHA: 7.8 g/g; m-MHA: 20.4 g/g) than those obtained for MBAs (p-MBA: 0.04 g/g; o-MBA: 6.2 g/g; m-MBA: 0.03 g/g). Besides, there is a large difference between o-MBA (6.2 g/g) and p-MBA (0.04 g/g). As a result, since the cysteine conjugates are not determinant in the ototoxic process of xylenes, the location of the methyl groups around the benzene nucleus could play a key role.

Animals↗

Threshold-duration function of the acoustic reflex in man.

The threshold-duration function of the acoustic reflex was investigated in 5 male and 5 female adult, normal-hearing humans and in 3 adult male subjects with hearing loss of cochlear etiology. Reflex threshold was obtained at stimulus durations of 10, 20, 50, 100, 200, and 500 msec and at frequencies of 500, 1 000, 2 000, 3 000, and 4 000 Hz. Three commercially available acoustic bridges were employed, the Madsen ZO-70 and Grason-Stadler 1720 electroacoustic bridges, and the Grason-Stadler-Zwislocki model 3 mechanical-acoustic bridge. A probe-tone frequency of 220 Hz was used in all measures. The reflex threshold-duration function for normal-hearing subjects was found to encompass a much greater range of intensity than the psychophysically assessed auditory threshold temporal integration function. A sex difference was found which may be explained by subclinical noise-induced cochlear pathology in the male subjects with subsequent truncation of the reflex threshold-duration function. The function was also found to be truncated in the 3 subjects with hearing loss diagnosed to be of cochlear etiology. The implications of these findings for control of stimulus duration in clinical reflex measurement was discussed.

Acoustic Stimulation↗

Hydrostatic pressure in the inner ear fluid compartments and its effects on inner ear function.

The present study summarizes the experimental findings obtained on the pressure in the inner ear fluids and on the effects of pressure changes on cochlear function in the guinea pig. Two types of pressures have to be distinguished in the inner ear fluid compartments: (i) hydrostatic fluid pressure and (ii) superimposed hydrodynamic high frequency (> 100 Hz) sound pressure oscillations. Hydrostatic pressure in the inner ear fluids in guinea pigs is in the order of 200 Pa (2 cm H2O) and shows slow (< 5 Hz) respiratory and pulsatory oscillations as well as considerable physiological variations in the range of -100 to +700 Pa. In normal ears, hydrostatic pressure in the perilymph equals pressure in the endolymph, and pressure changes applied to one compartment are immediately transmitted to the other one. A high compliance of Reissner's membrane seems to be the cause of this endolymphatic-perilymphatic pressure equalization. In experimental endolymphatic hydrops, a unique animal model for Meniere's disease, endolymphatic pressure is higher (100 Pa and above) than perilymphatic pressure. These pressure gradients occur only in late stages of hydrops, probably when Reissner's membrane has lost its high compliance after long standing distension. Positive endolymphatic-perilymphatic pressure gradients are secondary to and not the primary cause of hydrops formation. Changes of hydrostatic pressure do not affect auditory function as long as they stay in the physiological range. This includes the sudden loss of positive inner ear pressure that occurs in perilymph fistulas. The rationale for surgical repair of perilymph fistulas in patients in order to restore the hearing function thus becomes questionable. Other aspects of surgical repair, however, as e.g. prevention of labyrinthitis due to permanently open fistula, could not be investigated in this model, because in guinea pigs even large fistulas heal spontaneously within a few days. In experimental endolymphatic hydrops, deterioration of auditory thresholds was partially correlated to the presence of positive endolymphatic-perilymphatic pressure gradients. A change in pressure, however, occurred later than the first deterioration in auditory function. Therefore positive endo-perilymphatic pressure gradients may contribute to, but are not the only cause of hearing impairment.

Animals↗

Operant response in infants as a function of time interval following signal onset.

This study investigated the hypothesis that estimates of infant auditory threshold are lowered by extending the duration of individual test trials such that infants have more time to detect and respond to the acoustic signal. Forty 8- and 12-month-old infants were evaluated with an operant procedure to determine response latencies at four near-threshold levels. Resulting data were used to estimate the effect of trial duration on threshold by calculating the response performance that occurred at several intervals following signal onset. Findings indicate that most detection responses occurred in the initial 4 sec of the test trial, and use of an 8-sec trial interval yielded little gain in performance. The data reflect an insignificant shift (< 5.0 dB) in threshold as a function of extended trial intervals.

Acoustic Stimulation↗

Pure tone delayed auditory feedback: development of criteria of performance deterioration.

Delayed auditory feedback audiometry, employing pure tones and a keytapping task, was administered at sensation levels from -10 to +50 dB to a sample of the general adult population. Absolute and relative time error as well as pattern error criteria were established on the basis of the -10-dB performances. Ninety percent of the subjects demonstrated tapping errors at sensation levels within 10 dB of auditory threshold.

Adolescent↗

Determining the upper limits of stimulation for auditory steady-state response measurements.

OBJECTIVE: To determine the maximum stimulus levels at which a measured auditory steady-state response (ASSR) can be assumed to be a reliable measure of auditory thresholds. DESIGN: ASSR thresholds were measured at octave frequencies from 500 to 4000 Hz in 10 subjects with profound hearing loss. These subjects provided no behavioral responses to sound at the limits of pure-tone audiometers and at the limits of the stimulus levels produced by the ASSR device. Subjects were divided into two groups of five, with repeated measures obtained within the same session in one group and repeated measures obtained in a separate session on a different day in the other group. RESULTS: ASSR thresholds were observed in all 10 subjects at each of four frequencies and in both trials. On average, these ASSR thresholds were observed at 100 dB HL (SD = 5 dB). Because these responses were at least 18 to 22 dB below the limits of the equipment where all subjects had no behavioral responses, it is reasonable to conclude that the ASSRs were not generated by the auditory system. CONCLUSIONS: An artifact or distortion may be present in the recording of ASSRs at high levels. These data bring into question the view that there is a wider dynamic range for ASSR measurements compared with auditory brain stem response measurements, at least with current implementation.

Adult↗

Temporal integration of sound pressure determines thresholds of auditory-nerve fibers.

Current propositions of the quantity of sound driving the central auditory system, specifically around threshold, are diverse and at variance with one another. They include sound pressure, sound power, or intensity, which are proportional to the square of pressure, and energy, i.e., the integral of sound power over time. Here we show that the relevant sound quantity and the nature of the threshold can be obtained from the timing of the first spike of auditory-nerve (AN) fibers after the onset of a stimulus. We reason that the first spike is triggered when the stimulus reaches threshold and occurs with fixed delay thereafter. By probing cat AN fibers with characteristic frequency tones of different sound pressure levels and rise times, we show that the differences in relative timing of the first spike (including latencies >100 msec of fibers with low spontaneous rates) can be well accounted for by essentially linear integration of pressure over time. The inclusion of a constant pressure loss or gain to the integrator improves the fit of the model and also accounts for most of the variation of spontaneous rates across fibers. In addition, there are tight correlations among delay, threshold, and spontaneous rate. First-spike timing cannot be explained by models based on a fixed pressure threshold, a fixed power or intensity threshold, or an energy threshold. This suggests that AN fiber thresholds are best measured in units of pressure by time. Possible mechanisms of pressure integration by the inner hair cell-AN fiber complex are discussed.

Acoustic Stimulation↗

High lead exposure and auditory sensory-neural function in Andean children.

We investigated blood lead (B-Pb) and mercury (B-Hg) levels and auditory sensory-neural function in 62 Andean school children living in a Pb-contaminated area of Ecuador and 14 children in a neighboring gold mining area with no known Pb exposure. The median B-Pb level for 62 children in the Pb-exposed group was 52.6 micrograms/dl (range 9.9-110.0 micrograms/dl) compared with 6.4 micrograms/dl (range 3.9-12.0 micrograms/dl) for the children in the non-Pb exposed group; the differences were statistically significant (p < 0.001). Auditory thresholds for the Pb-exposed group were normal at the pure tone frequencies of 0.25-8 kHz over the entire range of B-Pb levels, Auditory brain stem response tests in seven children with high B-Pb levels showed normal absolute peak and interpeak latencies. The median B-Hg levels were 0.16 micrograms/dl (range 0.04-0.58 micrograms/dl) for children in the Pb-exposed group and 0.22 micrograms/dl (range 0.1-0.44 micrograms/dl) for children in the non-Pb exposed gold mining area, and showed no significant relationship to auditory function.

Adolescent↗