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Measures for the optimum estimation of audiometric thresholds from the auditory brainstem response potentials.

Auditory brainstem response potentials were recorded from normally hearing subjects using a wide range of stimulus intensities including a below-threshold condition. Various measures, including the traditional Jewett V (JV) amplitude, were taken from the recordings. The probability of incorrectly concluding that a response was present was found by analysing the distribution of the JV amplitude in the no-stimulus recordings and setting an amplitude of 100 nV as the criterion of whether or not a response is deemed to be present. This probability was used to define equivalent criteria for the other measures and evoked potential (EP) thresholds could then be found for each subject and stimulus by finding the lowest stimulus intensity at which the value of the measure being considered was at or above this criterion value. Two measures were found to give significantly lower and less variable EP thresholds than the others; JV amplitude taking into account the JV latency and a self-template measure involving the correlation between the response waveforms at a high stimulus intensity level and the test intensity level. The latter measure indicates that a template-matching method of threshold estimation might be as reliable for this purpose as the measurement of JV amplitude and has the potential diagnostic advantage over JV measurements that it could be readily used with a fully objective automatic threshold evaluation protocol. The probability of making a false-positive error was found to be disconcertingly high at 0.5 for single measures and 0.22 for complex measures. This underlines the need for replicates to be taken as this dramatically reduces the probability of large errors in threshold estimation.

Audiometry, Evoked Response↗

[Relations between pure-tone audiometry and cortical evoked auditory potentials].

Slow vertex response (SVR) audiometry is presently one of the methods of choice in objective auditory threshold assessment. The aim of this study was to evaluate, as objectively possible, the relationship existing between the thresholds of SVR and or pure tone audiometry (PTA). The study was carried out on twenty subjects with hearing losses of various degrees and types. While mean differences between SVR and PTA thresholds ranged between 6 to 13 dB, in some cases values over 30 dB were found. No statistically significant intra- and interindividual discrepancies were found, even though in some cases the thresholds were given different in evaluations by different examiners. No statistically significant difference in SVR versus PTA thresholds was found in patients with sensory-neural and conductive hearing loss, while in subjects with normal hearing the difference between the thresholds was greater. Our results suggest that SVR is a reliable technique in objective threshold evaluation but that in single cases its threshold cannot be directly compared to that of pure tone audiometry.

Audiometry, Pure-Tone↗

Reverse transduction measured in the isolated cochlea by laser Michelson interferometry.

It is thought that the sensitivity of mammalian hearing depends on amplification of the incoming sound within the cochlea by a select population of sensory cells, the outer hair cells. It has been suggested that these cells sense displacements and feedback forces which enhance the basilar membrane motion by reducing the inherent damping of the cochlear partition. In support of this hypothesis, outer hair cells show membrane-potential-induced length changes at acoustic rates. This process has been termed 'reverse transduction'. For amplification, the forces should be large enough to move the basilar membrane. Using a displacement-sensitive interferometer, we tested this hypothesis in an isolated cochlea while stimulating the outer hair cells with current passed across the partition. We show here that the cochlear partition distorts under the action of electrically driven hair cell length changes and produces place-specific vibration of the basilar membrane of a magnitude comparable to that observed near auditory threshold (about 1 nm). Such measurements supply direct evidence that cochlear amplification arises from the properties of the outer hair cell population.

Animals↗

Sensitivity of auditory brainstem response in acoustic neuroma screening.

Auditory brainstem response (ABR) is the reference screening technique for acoustic neuromas, but because of a few false negatives and the increasing performance of magnetic resonance imaging (MRI), its role as the standard method has been questioned. We assessed sensitivity of screening tests in 89 patients with surgically proven acoustic neuromas. Sensitivity of ABR was 92%; 94% for extracanalicular neuromas and 77% for intracanalicular neuromas. For stapedius reflex (SR), sensitivity was 84% and for caloric vestibular response (CVR) 86%. The combined sensitivity of ABR + SR was 97% and of ABR + RS + CVR 98%. For false negatives, the greatest diameter including the intracanalicular portion was always less than 18 mm, with a mean of 15 mm, and none of these tumours reached the brainstem. For patients with unilateral cochleo-vestibular deficit, we propose ABR and SR as first-line screening tests. These tests are repeated at 6 months and at 1 year in the case of normal results. MRI is ordered for patients whose auditory threshold is too low and for those whose ABR or SR results favour retrocochlear disease.

Caloric Tests↗

Effect of electrical stimulation of the crossed olivocochlear bundle on temporary threshold shifts in auditory sensitivity. I. Dependence on electrical stimulation parameters.

1. This study examines the effect on auditory desensitization of electrically stimulating the crossed olivocochlear bundle (COCB) at the floor of the fourth ventricle. Auditory desensitization was induced by a loud high-frequency pure tone exposure and measured as temporary threshold shifts (TTS) in the sensitivity of the compound action potential recorded from the cochlea. COCB stimulation simultaneous with the loud sound exposure reduced the TTS. This reduction was contingent on the COCB stimulus being presented as a continuous burst for the entire duration (1 min) of the exposure. 2. The reduction in TTS could be abolished by prior administration of strychnine. The action of strychnine on these TTS effects of continuous COCB stimulation paralleled its action on the classical COCB effects elicited by pulsed short COCB trains. If the action of strychnine on the classical COCB effects was allowed to reverse, then continuous COCB stimulation reduced TTS as effectively as before. 3. The most effective COCB stimulus was found to be one that was presented at a high rate of stimulation simultaneous with the exposure. The COCB effect on TTS was also found to be a tonic one; smaller but significant reductions in TTS could still be obtained with the exposure presented 5 min after COCB stimulation though not when the delay was 10 min. The tonic reductions in TTS appeared to occur without any persisting changes at the cochlea. Normal cochlear responses remeasured in the delay between the stimulus and exposure were not altered. 4. It was hypothesized that the persisting effect responsible for TTS reductions did not occur at the cochlea but at some central site facilitated by antidromic action potentials along the COCB fibers. Subsequent exposure to loud sounds would activate the central site primed by the prior COCB stimulus. This hypothesis was tested by stimulating the COCB alone as before, but then lesioning the fibers before presenting the exposure. Persistent cochlear effects of the COCB stimulus should have still resulted in a reduction in TTS. However, if the persistent effect was at a more central location, lesioning the fibers would allow afferent input to act at the facilitated central location but would not allow subsequent expression of COCB effects at the cochlea. In this case, no reductions in TTS could be expected--precisely the results that were obtained in these experiments. Thus the COCB system appeared to have a "memory" component facilitated by prior stimulation and activated by a subsequent exposure.

Acoustic Stimulation↗

Regulation of cricket phonotaxis through hormonal control of the threshold of an identified auditory neuron.

1. The phonotactic threshold of 3 to 5-day-old adult female Acheta domesticus and the threshold of the L1 auditory neuron drop progressively (Fig. 1). 2. Application of juvenile hormone III (JHIII) to 1-day-old females caused both the female's threshold for phonotaxis and the threshold of the L1 auditory neuron to drop 20 or more dB over the next 12 h (Figs. 3-4). 3. JHIII's effect on phonotactic threshold could be blocked by injection with a transcription (alpha-amanitin) or a translation blocker (emetine, Fig. 3). 4. Injection of emetine also prevented the JHIII induced drop in L1's threshold (Fig. 4). 5. Application of JHIII to the surface of, or microinjection of JHIII into one prothoracic hemiganglion caused the female to circle phonotactically away from the side of hormone addition at thresholds 25 to 35 dB lower than the pre-JHIII addition threshold within 2 h (Fig. 6). 6. Application of JHIII to the surface of both prothoracic hemiganglia, accompanied by microinjection of emetine into one hemiganglion resulted in the female emetine into one hemiganglion resulted in the female circling phonotactically toward the side receiving emetine injection, with a 25 to 35 dB drop in threshold (Fig. 6).

Animals↗

Carboplatin ototoxicity: an animal model.

A new animal model of ototoxicity is presented using intravenous carboplatin in adult chinchillas. A range of physiological and morphological effects was produced using doses calculated from the recommended therapeutic range (200-400 mg/m2). Auditory thresholds to tone pips stimuli were monitored using brain stem evoked responses (ABR). Cochlear histopathology was studied by light microscopy (LM) and ultrastructural hair cell abnormalities investigated with scanning electronmicroscopy (SEM). Carboplatin in this animal model predominantly affected the inner hair cells. This may provide an important model for the study of selective loss of the main afferent input in the auditory system.

Animals↗

Simultaneous recording and separation of early and middle latency auditory evoked potentials.

A method, consisting of wideband (1-5000 Hz) recording, dual artifact rejection (for both EEG and muscle artifacts) and separation of the EAEP by digital high-pass filtering of the averaged signal, is proposed for the simultaneous recording of early and middle latency auditory evoked potentials. The high-pass was realized by a simple recursive filter. The middle (MAEP) latency components were derivable directly from the wideband averaged signal without further filtering, thus avoiding wave form distortions. Through this method additional information on the afferent auditory system can be gained, and auditory threshold determination can be considerably improved. The proposed procedure is implementable on any computer-based EP system and does not require extra amplifiers, filters or separate test runs for the acquisition of the MAEP.

Brain↗

Ototoxicity, nephrotoxicity and pharmacokinetics of cisplatin and its monohydrated complex in the guinea pig.

PURPOSE: To evaluate and compare the ototoxicity and nephrotoxicity of cisplatin and cis-diammineaquachloroplatinum(II) ion (monohydrated complex of cisplatin, MHC, formed in vivo by hydrolysis of cisplatin) after their separate administration to guinea pigs. METHODS: A dose of 4 mg/kg body weight of MHC was deemed suitable for the toxicity evaluation after dose titration. Electrophysiological hearing thresholds (auditory brainstem response, ABR), plasma creatinine and weight were measured in three groups of animals before and after receiving MHC 4 mg/kg (0.0141 mmol/kg), cisplatin 4.24 mg/kg (0.0141 mmol/kg, i.e. equimolar dose) or cisplatin 8 mg/kg (0.0267 mmol/kg) as an i.v. bolus injection. Cisplatin and MHC were analysed using liquid chromatography with post-column derivatization. RESULTS: Administration of MHC 4 mg/kg caused a moderate ABR threshold shift, a significant increase in creatinine and a significant weight loss, changes similar to those seen after administration of cisplatin 8 mg/kg. Animals given cisplatin 4.24 mg/kg had a slight increase in creatinine, but had no ABR threshold shift and gained weight during the experiment. The pharmacokinetic parameters of cisplatin and MHC were estimated after administration of cisplatin 4.24 mg/kg and MHC 4 mg/kg. The area under the blood-ultrafiltrate concentration versus time curve (AUC) for cisplatin after administration of MHC 4 mg/kg was 23% (56+/-5.0 micro g.min.ml(-1)) (means+/-SD) of that after administration of cisplatin 4.24 mg/kg (240+/-25 micro g.min.ml(-1)). The AUC for MHC after administration of cisplatin 4.24 mg/kg was 20% (30+/-4.9 micro g.min.ml(-1)) of that after administration of MHC 4 mg/kg (149+/-26 micro g.min.ml(-1)). CONCLUSIONS: MHC 4 mg/kg causes ototoxicity, nephrotoxicity and weight loss when administered to guinea pigs. The toxic effects were similar to those seen after administration of cisplatin 8 mg/kg and higher than those seen after administration of cisplatin 4.24 mg/kg.

Animals↗

[Therapy of sensorineural hearing loss in the aged with arteriosclerotic disease: a comparison of hydroxyethyl starch and prostaglandin].

We assessed 42 patients (aged between 51 and 86 years, average age: 71.6 years) with chronic bilateral sensorineural hearing loss in old-age, who showed bilateral pathological loss of discrimination. This was a group of patients diagnosed with internal-angiological arteriosclerotic vascular disease (uni- or bilateral obliteration of the carotid artery, condition following a cerebral ischaemic attack or peripheral arterial occlusive disease). 21 patients received infusion treatment with hydroxyethylamylum (HAES-steril 10%), a further 21 patients were infused with prostaglandin (Prostavasin, PGE-1) for three weeks. Pure tone audiometric and speech audiometric assessments were carried out before and after the infusion treatment (minimal loss of discrimination, overall word discrimination). It was statistically shown that there was no significant improvement of the average auditory threshold between 0.5 and 8 kHz using hydroxyethylamylum and prostaglandin. However, the examination results verify an increase of the minimal loss of discrimination and an improvement of speech comprehension following therapy with hydroxyethylamylum and prostaglandin. Between these two substances no difference was to be proved statistically. Our therapeutic results can be explained by the following considerations: 1. An improved circulation of the inner ear and the auditory pathway is to be regarded as possible reason for the achievement of the therapeutic effect. 2. An influence on the transmitter system of the cochlea and the auditory pathway is conceivable.

Aged↗

Auditory evoked responses (AER) and augmenting-reducing phenomenon in patients with progressive supranuclear palsy (PSP).

Variations in amplitude and latency of P1, N1 and P2 waves of AER induced by increasing the stimulus intensity (augmenting-reducing) were measured in PSP patients and compared to those observed in normal subjects. The studied population included 17 patients (10 male, 7 female, mean age 66 +/- 8 yr) with a typical PSP symptomatology and 17 normal subjects (10 male, 7 female, mean age 66 +/- 9 yr). All subjects from both the groups showed a normal auditory threshold (less than 30 db SPL or a moderately increased threshold never exceeding 10 db SPL). Nine patients had normal BAER; 4 patients showed an abnormal III wave; 3 patients showed an abnormal V wave. One patient had a poorly individualized BAER. Latencies and amplitudes of P1, N1 and P2 waves derived from Cz and Fz (linked ear reference) were studied with 50, 60, 70 and 80 db intensities and for each patient slopes of amplitude-stimulus intensity and latency-stimulus intensity curves were studied. Although patients showed decreased AER amplitudes, the augmenting-reducing phenomenon was not different from controls regarding either latency or amplitude changes with increasing stimulus intensity. Previous studies had established a negative correlation between the augmenting-reducing responses and HVA levels in the cerebrospinal fluid (CSF). Similarity of augmenting-reducing mechanisms in PSP and normal subjects favors the hypothesis of unimpaired mesocortical and mesolimbic dopaminergic pathways in PSP. This hypothesis is also supported by postmortem studies using biochemical markers.

Aged↗

Ontogenetic changes in the response properties of individual, primary auditory afferents in the vocal plainfin midshipman fish Porichthys notatus Girard.

The auditory system of adult midshipman fish Porichthys notatus Girard is an important sensory receiver system used during intraspecific social communication to encode conspecific vocalizations, but the response properties and function of this system in the pre-adult stages are unknown. Midshipman fish, like other teleosts, use the saccule as the main acoustic end organ of the inner ear. In this study, we examined the discharge properties and the frequency response dynamics of auditory saccular afferent neurons in pre-adult midshipman (approximately 4-12 months of age) to determine whether encoding of auditory information, inclusive of conspecific vocalizations, changes across life history stages. Extracellular single unit recordings were made from saccular afferents while sound was presented via an underwater speaker. Comparisons with adult data show that the resting discharge rate and auditory threshold sensitivity increased with age/size, while temporal encoding of frequency did not show any significant shifts. The results indicate that the saccular afferents of juveniles, like those of non-reproductive adults, are best adapted to temporally encode the low frequency components (<or=100 Hz) of midshipman vocalizations. This report represents the first in vivo investigation of age-related changes in the encoding properties of individual auditory neurons for any fish species.

Acoustic Stimulation↗

[Brainstem auditory evoked potentials (BAEP) in the rabbit. Normal patterns].

Brain stem auditory evoked potentials using skin electrodes have been studied in rabbits. The obtained records are integrated by 6 consecutive waves ranging up to 10 ms. of latency time. The most important, constant and well-performed waves were the I, II and IV waves, which persist until the auditory threshold by 10 dB. The obtained results in 50 ears have been statistically treated. Subsequently, a normal pattern of the BAEP in rabbits has been performed as a base for upcoming papers.

Animals↗

Dissociation of fMRI activation and awareness in auditory perception task.

To investigate the relationship between activity in sensory cortex, and the experience of sensory stimuli, functional magnetic resonance imaging (fMRI) of temporal cortex was performed while subjects indicated their perception of speech sounds combined with noise. Auditory cortex activation was found to decrease with decreasing stimulus saliency. Speech stimuli presented at an intensity level near auditory threshold produced significant activation in temporal cortex even when subjects did not report perception of stimuli. These dissociations between simultaneously recorded neurophysiological and psychophysical measures suggest that stimulus-evoked cortical activity does not necessarily produce conscious perception.

Acoustic Stimulation↗

Confirmation of deafness in infancy.

AIM: To assess delay in confirming hearing impairment in infants identified by universal neonatal screening and to investigate the causes. PATIENTS: Infants identified from 25 199 babies screened from January 1992 to December 1997. METHODS: A two stage transient evoked oto-acoustic emission test (TEOAE), with a threshold auditory brainstem response (ABR) recording undertaken on those who failed. The screen identified infants with a permanent congenital hearing impairment (PCHI) averaging 40 dBnHL or worse in the best ear. Those with less impairment were also ascertained. The positive predictive value (PPV) of the ABR test and measures of delay between identification and eventual diagnosis were analysed. RESULTS: A targeted PCHI was found in 1.18/1000 neonates. The PPV of the ABR for confirming a targeted PCHI was 100% when the ABR threshold was >/= 80 dBnHL. Nine of 11 infants with this threshold had severe or profound permanent deafness. The delay from ABR to audiological certainty was about 1 month-diagnosis was confirmed around 3 months. There was uncertainty when the ABR was 40-80 dBnHL. The PPV was 60% and 8% when the ABR thresholds were 70 dBnHL and 50 dBnHL, respectively. 85 of 111 infants with ABR thresholds in this range had a temporary conductive impairment. Their early diagnosis depended upon the type and degree of hearing impairment and diagnosis was delayed to about 8 months in these infants. CONCLUSIONS: Hearing impairments identified by universal screening are delayed in all but those with severe or profound bilateral PCHI. This delay can be reduced by applying in early infancy a battery of audiological tests and requires further exploration.

Acoustic Impedance Tests↗

Influence of acoustic experience on the ontogeny of frequency generalization gradients in the chicken.

The role of auditory experience in the ontogeny of perceptual coding was investigated in hatching chickens. In Experiment 1, auditory frequency generalization gradients were determined by using a habituation-generalization paradigm and an orienting response. One-day and 3-4 day chicks were habituated to 800-Hz tones and then tested at five frequencies ranging from 800 to 1,000 Hz. One-day chicks displayed reliably flatter generalization gradients than 3-4-day chicks. In Experiment 2 an auditory deprivation method is described in which an ear impression compound was injected into the external ear. This method (a) is fully calibrated and provides approximately 40 dB of attenuation across a .125- to 4.0-kHz range, (b) appears to be fully reversible, and (c) is applicable prior to normal auditory experience as well as at subsequent stages. In Experiment 3, this method was used to investigate the effects of auditory deprivation on the "perceptual sharpening" described in Experimental 1. Chicks were deprived from Embryonic Day 18 1/2 to 3-4 days posthatch, at which time normal, deprived, and sham-operated chicks were tested as in Experiment 1. The generalization gradients of the deprived chicks were significantly flatter than those of the 3-4 day normal and sham-operated chicks and were similar to those of 1-day chicks. This effect cannot be attributed to (a) operative procedures, (b) changes in auditory thresholds, or (c) changes in response rate with age or condition. Thus the perceptual sharpening normally occurring between 1 and 3-4 days posthatch fails to occur during that time in the absence of a normal acoustic environment.

Acoustic Stimulation↗

Exploration of cochlear function by otoacoustic emissions: relationship to pure-tone audiometry.

The amplitudes, growth functions and detection thresholds of evoked otoacoustic emissions (EOE) were measured in 44 normally hearing subjects and 138 patients with two categories of cochlear dysfunctions: (a) acoustic trauma; and (b) presbycusis. Separate sets of experiments were also performed: (a) detection of stimulus frequency emissions; and (b) click EOE. EOE properties were studied around 2 kHz, 1 kHz and 0.75 kHz (+/- 0.1 kHz). A partial correlation and multivariate analysis was carried out to investigate the relationships between EOE properties and puretone auditory thresholds (from 0.25 to 8 kHz, half-octave steps). For each experiment and each frequency, only one highly significant correlation was found, linearly relating the n kHz EOE threshold with the hearing threshold at 2n kHz: there was a shift of about one octave between EOE amplitudes and audiometric data. This means that EOE thresholds give no direct information about the local cochlear state. A simplified model has been implemented, which assumes that EOE thresholds and amplitudes are proportional to the total number of residual active sites along the organ of Corti, i.e., to the total length of active basilar membrane towards the base of the cochlea. It is shown that this model accounts for the results revealed by the statistical analysis and closely fits the experimental data.

Acoustic Stimulation↗

High-frequency audiometric monitoring for early detection of aminoglycoside ototoxicity.

Treatment with aminoglycosides is known to cause irreversible hearing loss, typically affecting higher-frequency hearing first and progressing to lower frequencies. Standardized methodology has not been developed for early detection of ototoxicity. Serial conventional (0.25-8 kHz) and high-frequency (9-20 kHz) hearing threshold monitoring was done prospectively in 53 hospitalized patients administered aminoglycosides. Hearing loss occurred in 47% of the ears studied, with hearing loss first appearing in the high-frequency range in 71% of ears showing change. Analysis of data on an individual basis revealed a five-frequency range most susceptible to initial ototoxicity. Testing only this range would have resulted in early identification of 82% of ears showing change. Results confirm the critical need for serial auditory threshold monitoring encompassing high frequencies in patients receiving aminoglycosides. A shortened five-frequency monitoring protocol is presented and suggested for use with patients unable to tolerate lengthy audiometric testing procedures.

Amikacin↗