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Predicting pure-tone thresholds with dichotic multiple frequency auditory steady state responses.

The accuracy of dichotic multiple frequency auditory steady state in predicting pure-tone thresholds at 0.5, 1, 2, and 4.0 kHz compared to an ABR protocol (click and tone burst at 0.5 kHz) were explored in a group of 25 hearing-impaired subjects across the degree and configuration spectrum. Mean steady state thresholds were within 14, 18, 15, and 14 dB of the pure tones at 0.5, 1, 2, and 4 kHz, compared to the tone-burst ABR at 0.5 kHz pure-tone difference of 24 dB, and a click-evoked pure-tone (2-4 kHz) difference of 9 dB. Recording time for the steady state protocol was 28 minutes (+/- 11) compared to 24 minutes (+/- 9) of the ABR protocol. Degree of loss had a significant effect on steady state; configuration of hearing loss had a limited effect. Mf ASSR predicted thresholds with relative accuracy although some configurations showed discrepancies for low-frequency estimates.

Acoustic Stimulation↗

Further observations on the threshold model of latency for auditory neurons.

This paper examines the recent claim of Phillips, that the threshold model of latency is inadequate to account for the changes of latency of auditory cortical neurons in response to tones of different amplitudes and rise times. I argue that Phillips' analysis was based on an incorrect assumption and that he therefore rejected the model for the wrong reasons, though correctly, as the model is in fact inadequate, as demonstrated here and previously. The failure of the model has significant implications for signal processing in the auditory system.

Algorithms↗

The effects of tempol, 3-aminobenzamide and nitric oxide synthase inhibitors on acoustic injury of the mouse cochlea.

Oxygen free radicals have been implicated in the pathogenesis of acoustic injury of the cochlea. The purpose of this study was to evaluate the effects of tempol (a superoxide anion scavenger), 3-aminobenzamide (a poly (ADP-ribose) synthetase (PARS) inhibitor), N-nitro-l-arginine (a non-selective nitric oxide synthase (NOS) inhibitor), 7-nitroindazole (a selective neuronal NOS inhibitor) and aminoguanidine (a selective inducible NOS inhibitor) on acoustic injury. Mice were exposed to a 4 kHz pure tone of 110-128 dB SPL for 4h. Tempol, 3-aminobenzamide or N-nitro-l-arginine was intraperitoneally administered immediately before the onset of acoustic overexposure, while 7-nitroindazole or aminoguanidine was intraperitoneally administered every 12h starting immediately before the onset of acoustic overexposure. The threshold shift of the auditory brainstem response (ABR) and hair cell loss were then evaluated one and two weeks after acoustic overexposure. Tempol and 3-aminobenzamide significantly protected the cochlea against acoustic injury, whereas the NOS inhibitors did not exert any protective effect. These findings suggest that reactive oxygen species and PARS are involved in acoustic injury of the cochlea. However, further study is necessary to elucidate the roles of nitric oxide and nitric oxide synthase in acoustic injury.

Analysis of Variance↗

Auditory-nerve spontaneous rates vary predictably with threshold.

The variation of spontaneous rate with auditory nerve thresholds is compared with predictions from a simple assumption: that spontaneous and driven activity are basically similar, both being evoked by inner hair cell transmembrane potential. Under this view, spontaneous activity is seen as a response to a standing current within the hair cell and should therefore vary with threshold in a manner predictable from measured rate-intensity functions. A method for comparing spontaneous rates of fibres with differing thresholds is developed and applied to previously-collected data. The results show that spontaneous rates are quite consistent with the hypothesis, indicating no need for more complicated theories of spontaneous activity.

Action Potentials↗

Effect of protective agents against cisplatin ototoxicity.

HYPOTHESIS: The goals of this investigation were to compare the efficacy of three protective agents against cisplatin-induced elevation of auditory brainstem response (ABR) thresholds and to examine whether these protective agents prevent cisplatin-induced alterations of the antioxidant defense system in the cochlea of the rat. BACKGROUND: Cisplatin is an ototoxic antitumor agent. Previous animal studies have shown that cisplatin administration causes an elevation of ABR thresholds. These auditory changes are accompanied by alterations in the concentration of glutathione and the antioxidant enzymes in the cochlea. The authors' previous work has indicated that the protective agent diethyldithiocarbamate (DDTC) prevents decrease in glutathione (GSH), alteration of antioxidant enzyme activity, and disruption of cochlear function with cisplatin administration. METHODS: Wistar rats were sedated and underwent pretreatment ABR testing using clicks and tone burst stimuli at 8, 16, and 32 kHz. Control rats received saline by intraperitoneal (i.p.) injection. Positive control rats were administered cisplatin 16 mg/kg i.p. Three groups of rats received protective agents in combination with cisplatin. The DDTC-protected rats were given 600 mg/kg of DDTC subcutaneously 1 hour after cisplatin. Animals protected by 4-methylthiobenzoic acid (MTBA) were given 250 mg/kg of this agent i.p. 30 minutes before cisplatin. Animals protected with ebselen were given 16 mg/kg i.p. one hour before cisplatin. The ABR thresholds were recorded 72 hours after cisplatin administration in all groups. Cochleas were removed, and extracts of the tissues were analyzed for GSH, activities of antioxidant enzymes (superoxide dismutase [SOD], catalase, glutathione peroxidase, and glutathione reductase) and malondialdehyde (MDA) (as an index of lipid peroxidation). RESULTS: Cisplatin-treated rats had significant ABR threshold shifts, ranging from 27 to 40 dB. Rats administered each of the three protective agents in combination with cisplatin had ABR threshold shifts of <10 dB. The cochleae of rats administered cisplatin alone had nearly a 50% depletion of glutathione and about a 50% reduction in the activities of SOD, glutathione peroxidase, and glutathione reductase, while catalase activity was reduced to 70% of control values. These changes were accompanied by a reciprocal elevation of MDA of 165%. These changes, namely, the depletion of GSH and antioxidant enzyme activity and the elevation of MDA in the cochlea, were largely attenuated by the administration of the protective agents tested. CONCLUSION: These findings suggest that cisplatin ototoxicity is related to lipid peroxidation and that the use of protective agents prevents hearing loss and lipid peroxidation by sparing the antioxidant system in the cochlea. These results suggest the possibility that the clinical use of protective agents could effectively reduce or prevent damage to the inner ear of patients receiving cisplatin chemotherapy, provided that the antitumor effect is not altered.

Adjuvants, Immunologic↗

The automated prediction of hearing thresholds in sleeping subjects using auditory steady-state evoked potentials.

OBJECTIVE: To examine the relationship between auditory steady-state evoked potentials (SSEPs) and behavioral thresholds in sleeping subjects. DESIGN: 60 adults and children with hearing thresholds ranging from normal to profound were selected on the basis of appropriate audiograms. Behavioral audiograms were determined at the octave frequencies 250-4000 Hz. These behavioral thresholds were then compared with the SSEP thresholds obtained during natural sleep for adults, or natural or sedated sleep for children. RESULTS: A strong relationship between behavioral and SSEP thresholds was observed. The strength of the relationship increased with increasing frequency and increasing degree of the loss. On the basis of these data, the prediction of behavioral thresholds from SSEP levels was determined. It was found that the standard deviation of the error in this prediction decreased with increasing frequency and increasing degree of the loss. There was no significant age effect in the results obtained at any of the frequencies. CONCLUSION: The results suggest the SSEP technique can be used as a predictor of behavioral threshold in adults and children at the frequencies 250-4000 Hz.

Adult↗

Masker phase effects in normal-hearing and hearing-impaired listeners: evidence for peripheral compression at low signal frequencies.

The presence of cochlear-based compression at low frequencies was investigated by measuring phase effects in harmonic maskers. In normal-hearing listeners, the amount of masking produced depends strongly on the phase relationships between the individual masker components. This effect is thought to be determined primarily by properties of the cochlea, including the phase dispersion and compressive input-output function of the basilar membrane. Thresholds for signals of 250 and 1000 Hz were measured in harmonic maskers with fundamental frequencies of 12.5 and 100 Hz as a function of the masker phase curvature. Results from 12 listeners with sensorineural hearing loss showed reduced masker phase effects, when compared with data from normal-hearing listeners, at both 250- and 1000-Hz signal frequencies. The effects of hearing impairment on phase-related masking differences were not well simulated in normal-hearing listeners by an additive white noise, suggesting that the effects of hearing impairment are not simply due to reduced sensation level. Maximum differences in masked threshold were correlated with auditory filter bandwidths at the respective frequencies, suggesting that both measures are affected by a common underlying mechanism, presumably related to cochlear outer hair cell function. The results also suggest that normal peripheral compression remains strong even at 250 Hz.

Acoustic Stimulation↗

Modeling distortion product otoacoustic emission input/output functions using segmented regression.

Distortion product otoacoustic emissions (DPOAEs) are low-level acoustic signals, the detection of which involves extraction from a background of noise. Boege and Janssen [J. Acoust. Soc. Am. 111, 1810-1818 (2002)] described a method for modeling the presence and growth of these responses. While improving growth function parameter estimation, this technique excludes a significant fraction of the data (especially low-level responses), and relies on ad hoc model fit acceptance criteria. The statistical difficulties associated with these limitations are described, and a weighted segmented linear regression model that avoids them is proposed. A simple test is presented for the presence of DPOAE growth. This technique is compared to that of Boege and Janssen in a dataset of 9 556 input/output (I/O) functions collected over 4 years on 866 ears from 379 construction apprentices and 63 age-matched controls. Comparisons are made on the entire dataset and within audiometric hearing loss categories. Segmented regression avoids the statistical pitfalls of the previous method, allows estimation of the threshold and slope of auditory response on a far greater number of I/O functions, and improves estimation of these parameters in this dataset. The potential for this method to yield more sensitive metrics of hearing function and compromise is discussed.

Acoustic Impedance Tests↗

Improved contingent negative variation audiometry.

In earlier reports we described contingent negative variation audiometry (CNV-A) and explored the accuracy of the method used in clinical conditions. Amplitude was found to be the factor which determines the accuracy of CNV-A. With this study we aimed to increase the amplitude of the CNV so as to improve the accuracy of CNV-A. The amplitude of the CNV is dependent on the content of the information of the S2 stimulus in the CNV paradigm. For this purpose we used a light stimulus (red or green) for the S2. The patient had to recognize the stimulus and act accordingly. The tests were performed on 12 volunteers in whom we simultaneously registered the CNV and the slow vertex response. The amplitude of the CNV was on average higher than with the previous CNV-A methods. The mean value of the absolute difference of the results between CNV-A and subjective tonal audiometry (ADG) was 6.9 +/- 5.5 dB. The mean difference between the results of both methods, however, was only 4.3 +/- 7.8 dB. The new CNV-A method is more accurate than the previous one. Nevertheless, we believe that not all possibilities for the improvement of the method have been explored. By taking into account the psychological factors which influence the amplitude of the CNV, and with a better computer analysis of the recordings, it will probably be possible to obtain even more accurate objective data on the threshold of perception of auditory stimuli with the aid of CNV-A.

Adult↗

Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of auditory nerve output after threshold recovery.

BACKGROUND: Acoustic stress can alter cochlear function even in the absence of permanent threshold elevation; however, synaptic consequences of transient acoustic stimulation remain incompletely understood. OBJECTIVE: This study aimed to investigate whether transient acoustic stimulation induces changes in the auditory nerve output and cochlear ribbon synapse morphology following hearing threshold recovery. METHODS: Young adult CBA/CaJ mice were exposed to band-limited acoustic stimulation (45-2,000&#xa0;Hz, 95&#xa0;dB SPL, 2&#xa0;h). Auditory brainstem responses (ABRs), hair cell and spiral ganglion neuron survival, and synaptic morphology were evaluated before exposure and up to 2&#xa0;weeks post-exposure. RESULTS: ABR thresholds were transiently elevated immediately after exposure but largely recovered by 1&#xa0;day post-exposure. In contrast, ABR wave I amplitudes significantly increased after threshold recovery across multiple test frequencies. Ribbon-associated puncta in both inner and outer hair cell regions exhibited biphasic temporal changes, with an initial decrease immediately after exposure followed by an increase at 1&#xa0;day post-exposure. The ribbon-associated punctal area also increased after exposure and remained elevated at later post-exposure time points. No significant loss of hair cells or spiral ganglion neurons was observed. Exploratory genomic analysis suggested enrichment of pathways related to metabolic defense and cellular stress responses. CONCLUSIONS: Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of peripheral auditory nerve output without overt cellular degeneration. These findings support a model in which early cochlear responses to acoustic perturbation include adaptive synaptic plasticity and gain regulation, extending current concepts of noise-induced cochlear change beyond irreversible synaptic loss.

Animals↗

Effect of bilateral auditory cortex lesions on absolute thresholds in Japanese macaques.

1. The behavioral audiograms of four Japanese macaques (Macaca fuscata) were assessed before and after receiving two-stage bilateral lesions of auditory cortex. Thresholds were assessed for each ear with the use of insertion earphones. 2. The bilateral lesions resulted in a large initial hearing loss followed by partial recovery that left the animals with a permanent hearing loss in both ears. 3. The initial hearing loss consisted of a total insensitivity to sound in the ear contralateral to the second lesion with limited hearing in the other ear. However, the animal with the most complete lesion was initially unable to hear sound in either ear. Broadband noise was often more effective in eliciting a behavioral response than tones. 4. Partial recovery occurred in all animals and was observed as early as the first week after surgery. Most of this recovery occurred during the first 3-7 wk after surgery. This rapid phase of recovery was sometimes followed by a more gradual phase although thresholds were still elevated after 94 wk. 5. The permanent hearing loss, which averaged from 30 to 44 dB, was not constant across frequency. Threshold shifts were smallest at 63 Hz and progressively increased with frequency to a maximum loss from 8 to 25 kHz with slightly less loss at 32 kHz. 6. Analysis of the psychophysical functions and threshold stability gave no indication of any nonsensory deficits in attention or vigilance. 7. These results, taken with those of previous experiments, indicate that each hemisphere is primarily involved in the detection of sound in the contralateral ear and secondarily involved in detection in the ipsilateral ear. This arrangement differs from that seen in sound localization where each hemisphere is involved with the contralateral hemifield as opposed to the contralateral ear. Thus it appears that the functional organization of auditory cortex for sound localization is different from that for the detection and identification of sound itself.

Animals↗

The deterioration of hearing with age: frequency selectivity, the critical ratio, the audiogram, and speech threshold.

The frequency selectivity of the auditory system was measured by masking a sinusoidal signal (0.5, 2.0, or 4.0 kHz) or a filtered-speech signal with a wideband noise having a notch, or stopband, centered on the signal. As the notch was widened performance improved for both types of signal but the rate of improvement decreased as the age of the 16 listeners increased from 23 to 75 years, indicating a loss in frequency selectivity with age. Auditory filter shapes derived from the tone-in-noise data show (a) that the passband of the filter broadens progressively with age, and (b) that the dynamic range of the filter ages like the audiogram. That is, the range changes little with age before 55, but beyond this point there is an accelerating rate of loss. The speech experiment shows comparable but smaller effects. The filter-width measurements show that the critical ratio is a poor estimator of frequency selectivity because it confounds the tuning of the system with the efficiency of the signal-detection and speech-processing mechanisms that follow the filter. An alternative, one-point measure of frequency selectivity, which is both sensitive and reliable, is developed via the filter-shape model of masking.

Adult↗

The relationship between auditory brainstem response and behavioral thresholds in normal hearing infants and adults.

The nature of age-related improvements in auditory sensitivity was explored by comparing behavioral and auditory brainstem response (ABR) thresholds in 3- and 6-month-old infants and in adults. Thresholds were estimated for tone pips at 1, 4, and 8 kHz, presented at a rate of 13.3/s. The time course of development of the two response measures was compared, and the correlation between thresholds for individual subjects was examined. Infant ABR threshold was adultlike at all frequencies, even among 3-month-olds. Infant behavioral thresholds were elevated relative to adult thresholds. Between 3 and 6 months, significant improvement occurred in the 8-kHz behavioral threshold, but no improvement occurred at other frequencies. This difference between ABR and behavioral measures in developmental time course suggests that peripheral sensitivity is not a major determinant of behavioral threshold elevation during infancy. The correlation between behavioral and ABR thresholds was significant at 4 kHz for 3-month-olds and at 8 kHz for adults. This suggests that variability in sensory function at these frequencies contributes to both behavioral and ABR thresholds, although other factors are likely to be involved as well.

Acoustic Stimulation↗

An active process in cochlear mechanics.

A model for cochlear mechanics is proposed to take account of its two systems, one passive and one active. The classical passive system stimulates the inner hair cells directly at levels above about 40 dB SL. At intensities below about 60 dB an active process, the 'cochlear amplifier' (CA), somehow provides additional energy that enhances the vibration of a narrow segment of the basilar membrane near the apical foot of the familiar, traveling wave envelope. The outer hair cells are essential for CA. The active system acts like a high-Q acoustic resonator, and it accounts for the great sensitivity and sharp tuning expressed by the 'tips' of neural tuning curves. The tips are selectively vulnerable to anoxia, noise exposure and other trauma. The CA model explains the detection of small differences in time as well as in frequency, the dual character of the electrocochleogram, recruitment of loudness in cochlear hearing impairment, the long latency of normal neural responses near threshold, acoustic emissions (both stimulated and spontaneous) and the locus of TTS in the frequency range above the exposure tone. Both the classical high-intensity system and the active low-level CA system are highly nonlinear and they combine to compress the great dynamic range of hearing into a much narrower range of mechanical movement of the cilia of the inner hair cells. The mechanism of CA is unknown, and the problem remains of how its action can be triggered by submolecular movements near threshold.

Auditory Threshold↗

Objective detection of auditory evoked potentials. Comparison of several statistical tests in the frequency domain by means of Monte Carlo simulations.

Fully objective assessment of the hearing threshold by auditory evoked potentials requires an objective detection of these responses by means of suitable statistical tests. The Rayleigh test, Watson's U2 test, Kuiper's test and Hodges-Ajne's test check the phase angle distribution of a Fourier harmonics in a sample of stimulus-related EEG epochs. The modified Rayleigh test includes, in addition to the phase angles, the amplitude information in the form of ranks of the spectral amplitudes. To compare the signal detection performance of these tests, estimates of the probability density functions were calculated by means of extensive Monte Carlo simulations. From the probability density functions, the sensitivity of the tests was calculated and receiver operating characteristics (ROC) were constructed. The modified Rayleigh test appeared to be the most powerful test, followed by the Rayleigh test and Watson's U2 test. The application of Kuiper's test and Hodges-Ajne's test as well is not to be recommended for AEP detection.

Auditory Threshold↗