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Effects of electrical stimulation of efferent olivocochlear neurons on cat auditory-nerve fibers. III. Tuning curves and thresholds at CF.

In order to study the effects of efferent activity, olivocochlear efferents were stimulated with an electrode in the fourth ventricle at the decussation of the crossed olivocochlear bundle (midline-OCB stimulation) or with an electrode at the brainstem origin of medial efferents (MOC stimulation). Tuning curves, or similar measures of threshold, were obtained from auditory-nerve fibers in the presence or absence of efferent stimulation. Efferent stimulation raised the thresholds of fibers for tones at the characteristic frequency (CF) by an amount which varied with the spontaneous rate (SR) of the auditory-nerve fiber. On the average, high-SR fibers had the smallest threshold shifts, and low-SR fibers had the largest threshold shifts. The distribution of threshold shifts as a function of CF peaked at CFs of 3-8 kHz for high-SR and medium-SR fibers but appeared to peak at higher CFs for low-SR fibers. Within the high-SR or medium-SR groups, the fibers with the lowest thresholds had the largest threshold shifts. Efferent stimulation decreased the Q20 of the tuning curves from most fibers (i.e. it made the tuning curves wider), but increased the Q20 from some fibers with CFs below 2 kHz. For fibers with CFs above 4 kHz, efferent stimulation shifted the tuning-curve tails to higher sound levels by about 1 dB on the average. The qualitative patterns of the effects due to midline-OCB stimulation or to MOC stimulation were similar. The distribution of high-SR threshold shifts vs. CF appears to be displaced apically in the cochlea compared to the distribution of MOC endings on outer hair cells. This can be understood in terms of efferent activity depressing basilar membrane motion and affecting regions at, and apical to, the activated efferent synapses. To explain the low-SR threshold shifts, an additional way in which efferent activity inhibits responses appears to be required. The data are consistent with one function of the medial efferents being to raise the thresholds of auditory-nerve fibers and thereby adjust the effective range of the auditory system.

Animals↗

Auditory brain-stem response and hearing threshold in cerebellopontine angle tumours.

The auditory brain-stem responses (ABR) in 19 patients with confirmed cerebellopontine angle tumours are evaluated in relation to the hearing threshold as obtained by pure-tone audiometry. ABR pathological alterations, in terms of either absence or presence of components, appear to relate to the suprathreshold stimulus intensity and to match the changes which can be observed in subjects with normal hearing, when stimulated at the equivalent suprathreshold intensity. Of the diagnostic indexes considered (I-V interval, IT5, delta V), IT5 and delta V could be evaluated in the largest patient population. They may be used in combination to enhance their sensitivity in retrocochlear lesion detection.

Audiometry↗

Na+,K+-ATPase and Ca2+-ATPase activities in the cochlear lateral wall following surgical induction of hydrops.

Na+,K+-ATPase and Ca2+-ATPase activities have not been studied quantitatively in the cochlea affected by endolymphatic hydrops. The present study was designed to measure quantitatively the Na+,K+-ATPase and Ca2+-ATPase activities in the cochlear lateral wall and the threshold of auditory brainstem response (ABR) for guinea pigs in the early stages (=2 months) of experimentally induced endolymphatic hydrops. A significant negative association was demonstrated between Ca2+-ATPase activity and the change in ABR threshold for hydropic cochleae (P=0.014), but not for control cochleae (P=0.123), although no such significant association was revealed between Na+,K+-ATPase activity and any change in ABR threshold for both hydropic cochleae (P=0.751) and control cochleae (P=0.352). A significant increase in Ca2+-ATPase activity in the cochlear lateral wall was observed for the hydropic ear, in which normal ABR thresholds were maintained, as compared to the control ear. On the contrary, a mild decrease in Ca2+-ATPase activity in the cochlear lateral wall was observed for the hydropic ear, in which ABR thresholds increased significantly. The present findings suggest that alterations of Ca2+-ATPase activity in the cochlear lateral wall may implicate disturbed calcium-homeostasis in the inner ear, resulting in hearing dysfunction in the early stages of experimentally induced endolymphatic hydrops.

Animals↗

Hypercholesterolemia and auditory dysfunction. Experimental studies.

Rabbits were used for the long-term study of auditory function associated with experimental hypertension and hypercholesterolemia. Auditory dysfunction (threshold changes of sound evoked responses) was monitored with an electrode, chronically implanted into the contralateral inferior colliculus. Hypertension was created using the renal encapsulation technique. Auditory function in the hypertension trial demonstrated a dip at higher frequencies as well as improvement at lower frequencies. One gram of cholesterol fed daily for three months was capable of making rabbits atherosclerotic. Cholesterol-fed rabbits showed increasing auditory dysfunction over time at all frequencies. When experimental hypertension was combined with hypercholesterolemia, the auditory changes appeared additive. This work, although in preliminary stages, seems to provide experimental evidence that auditory dysfunction is associated with cholesterol diet.

Animals↗

Evidence for direction-specific channels in the processing of frequency modulation.

Evidence is provided for the existence of at least three feature-specific channels in the auditory system. Thresholds for the detection of small repetitive or nonrepetitive frequency changes were measured following various adapting stimuli using a 2IFC procedure in two subjects at 1 kHz. Thresholds for single linear upward frequency sweeps (up sweeps) were increased by a factor of 2 to 3 following exposure to repetitive (8 Hz) up sweeps but not following exposure to down sweeps or tone bursts; correspondingly, thresholds for down-sweep stimuli were increased only by down sweeps. Sinusoidal FM test stimulus thresholds were elevated by both up-sweeps and down-sweeps and to a lesser extent by tone bursts. These results suggest the existence in the auditory system of channels specific to upward FM, downward FM, and probably repetition rate.

Acoustic Stimulation↗

Electromagnetic stimulation of the auditory system of deaf patients.

Electromagnetically induced auditory perception was investigated in 18 deaf patients who were candidates for cochlear implants. In the extracranial magnetic stimulation (EMS) procedure, patients were stimulated with time-varying magnetic field brief pulses from a coil positioned at the i) auricle, ii) the mastoid, and iii) the temporal lobe area. EMS elicited auditory sensations in 26 ears (of 14 patients/subjects). The lowest threshold of auditory sensation (TAS) was found to be at the 20% EMS level, with a range of 20-50% of the maximum level (2.0 Tesla), and approximately equal sensitivity in each coil position. Eleven of the subjects hearing EMS-induced sound perceived changes in pitch while 6 heard "clicks" or clicks and tones. Spearman Rho correlation analysis showed a mild negative correlation between the EMS/TAS and the pre-implant FFA, best tone threshold (BTT), and direct promontorial electrical stimulation (ES) thresholds at 250 Hz and 500 Hz. No correlation was found between EMS or ES and performance on the pre-implant or post-implant psychacoustic tests (MAC VIII or 3-Digit speech tests) or the measurements of the thickness of cutaneous and osseous tissue from the stimulation sites at the mastoid and ear canal to the cochlear and 8th nerve. A fair positive correlation was found between the EMS/TAS and the post-implant (6 months) ES threshold when the electrodes allocated the 500 Hz frequency range were stimulated. A mild positive correlation between the pre-cochlear-implant promontorial electrical stimulation (ES) at 250 Hz and the four frequency tone average (FFA: 0.5, 1, 2, 4 kHz) was also found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Interaction between continuous and impulse noise: anatomic and functional evaluation in relation to the intensity of the exposure].

Interaction between continuous and impulse noise was studied. One group of chinchillas was exposed to octave band of noise of 0.5 kHz 95 dB SPL intensity. Three groups were exposed to impulse noises of 113, 119 and 125 prak SPL emitted at 1 imp/sec, 1 imp/4 sec and 1 imp/16 sec respectively. Three groups were exposed to noise created by a combination of above continuous and impulse noises. All exposures lasted for 5 days. Hearing thresholds were measured in 35 animals using auditory evoked potentials. The combined continuous and impulse noises showed equal energy contents, but the groups exposed to 119 and 125 dB impulse noise intensities developed an exacerbation of PTS and cell hair loss. Therefore, the critical level, under which the damage associated with noise exposure is related to the total noise energy (Equal Energy Hypothesis) was reduced when impulse noise was added to continuous noise.

Animals↗

Some non-auditory correlates of the hearing threshold levels of an aviation noise-exposed population.

In a retrospective analysis of data collected during the 1963 followup of the NAMRL Thousand Aviator Study, two hearing level groups were identified, normal and impaired, and compared along 33 non-auditory dimensions. It was discovered that these two equally noise-exposed groups could be differentiated according to their smoking history and eye color. That is, the impaired hearing group reported smoking more cigarettes for a greater period of time than did the members of the normal hearing group. Furthermore, blue-eye individuals were over-represented in the impaired hearing group and under-represented in the normal hearing group, whereas the reverse was true for brown-eyed aviators. This latter finding is consistent with reports linking temporary hearing loss and eye color. There was 31 other physical, psychological, and sociological measures which failed to appear differentially in the two groups.

Adult↗

Frequency selective effects of alcohol on auditory detection and frequency discrimination thresholds.

In the first of two experiments, the effects of ethyl alcohol on monaural and binaural thresholds for pure tones were measured for a range of frequencies. The results showed a frequency-specific effect in which low frequencies were more severely affected than higher ones. Also, monaural thresholds tended to be more affected by alcohol than binaural ones. The second experiment extended this exploration by measuring frequency discrimination at several different frequencies. In this case, we also obtained a frequency-dependent effect: the increase in discrimination thresholds above 1000 Hz was three times greater than that for lower frequencies. The data suggest that the choice of stimuli may influence the ability to detect changes in auditory performance after alcohol and may account in part for the differences among earlier studies. The results are consistent with the hypothesis that alcohol is acting centrally, at the level of mechanisms involved in the temporal and binaural summation of auditory signals, rather than influencing peripheral structures.

Adult↗

AAV gene therapy for autosomal recessive deafness 9: a single-arm trial.

Gene therapy for congenital deafness has shown promising results in children but lacks data in older populations. We conducted a single-arm trial of adeno-associated virus (AAV)-OTOF gene therapy using the Anc80L65 capsid in ten participants with autosomal recessive deafness 9 aged 1.5 to 23.9 years at five sites in China. The primary endpoints were safety and tolerability within 5 years, and secondary endpoints assessed auditory function. Initial findings from the ten patients with 6-12 months of follow-up, including one patient who received two injections, revealed that the therapy was well tolerated, with 162 grade I/II adverse events. Decreased neutrophil percentage was the most common event (16 of 162). All ten participants had at least 6 months of follow-up and improved their pure-tone-average hearing level from baseline 106 ± 9 (mean ± s.d.) to 52 ± 30 decibels (dB). Other secondary endpoints showed similar improvements, including the average click auditory brainstem response (ABR) threshold, the tone-burst ABR threshold and the auditory steady-state response (101 ± 1 to 48 ± 26 dB, 91 ± 4 to 57 ± 19 dB and 80 ± 14 to 64 ± 21 dB, respectively). Post hoc analyses were conducted to evaluate the timecourse and factors contributing to the hearing improvement. Therapeutic effect was rapid, taking 1 month to achieve most of the overall hearing improvement. On an individual level, click and tone-burst ABR thresholds, but not the auditory steady-state response, reliably predicted the behavioral pure-tone-average thresholds after 4 months (R2 = 0.68, 0.73 and 0.17, respectively). An age-dependent therapeutic effect was observed, with optimal outcomes in 5- to 8-year-olds. These preliminary results show that AAV-OTOF was safe and well tolerated in patients ranging from toddlerhood to adulthood. The trial remains ongoing and requires extended follow-up to confirm the long-term safety and efficacy. ClinicalTrials.gov registration: NCT05901480 .

Humans↗

Lack of association between otoacoustic emissions and hearing difficulty in subjects with normal hearing thresholds.

Evoked otoacoustic emissions (EOAE) are a sensitive indicator of subtle cochlear damage and hence might explain why some people complain of excessive difficulty understanding speech in a background of noise, despite having normal hearing thresholds. This phenomenon has been termed "Obscure Auditory Dysfunction" (OAD). Recorded EOAE waveforms from a group of 50 OAD patients were compared with those from a group of 50 matched controls. No significant difference could be found between the two groups across a range of objective and subjective descriptors of the EOAEs. Any cochlear component of OAD does not appear to affect the function of the outer hair cells sufficiently to modify EOAEs materially.

Auditory Threshold↗

Threshold characteristics of the human auditory brain stem response.

Auditory brain stem responses (ABRs) were recorded from ten normal-hearing subjects in response to 100-microseconds clicks from a TDH 49 earphone at a rate of 48 pps and at levels randomly varied in 2-dB steps between 34 and 52 dB p.e. SPL. At each level, 10 000 epochs were averaged with use of a weighted concept and a running estimate was made of the signal-to-noise ratio (SNR). This quantity was used to detect the presence of the ABR and the median threshold was found at 38 dB p.e. SPL. The mean averaged background noise level was 11.3 nVrms, and the "true" ABRrms amplitude function crossed this value at 35.5 dB p.e. SPL, which indicates the level where the SNR = 1. By extrapolation, it was found that the ABR amplitude became zero at 32 dB p.e. SPL. The perceptual thresholds of the click were estimated by means of a modified block up-down procedure, and the median value was found at 33 dB p.e. SPL. The slope of the amplitude function and the magnitude of the averaged background noise are the two factors responsible for the ABR threshold sensitivity, which thus depends on both physiological and technical parameters. Therefore, these have to be considered together with the method of detection when the ABR is used to indicate the hearing sensitivity.

Auditory Threshold↗

Fibromyalgia as a disorder of perceptual organization? An analysis of acoustic stimulus processing in patients with widespread pain.

We examined to what extent patients with fibromyalgia differ from painfree control subjects in the perception and processing not only of somatosensory but also of external stimuli. For this purpose the acoustic perception of 30 patients with fibromyalgia was compared with that of 36 generally pain-free age and gender matched subjects. The groups were also controlled for organic disease of pathological dysfunction of the ear and auditory nerves. Thresholds of unpleasantness and hearing thresholds were determined autiometrically for various frequencies. In addition the participants rated their experience of daily noise, vulnerability to acoustic stress, and functional and affective complaints associated with fibromyalgia. As expected the results show reduced unpleasantness thresholds for all frequencies and a nonsymptomatic hearing loss for higher frequencies. The elevated hearing threshold correlated significantly with experience of noise at the place of work, which was also elevated in the fibromyalgia group. Generalized pain had a high impact on the interaction between threshold of unpleasantness and daily noise experience. We interpret the differences in thresholds of hearing and of unpleasantness in patients with fibromyalgia as a form of either preconscious or conscious acts to protect against disturbing stimulation. Our results support the notion of a generalized disturbancy of perceptual thresholds in patients with fibromyalgia not restricted to the perception of pain.

Adult↗

Dietary vitamin C supplementation reduces noise-induced hearing loss in guinea pigs.

Vitamin C (ascorbate) is a water-soluble, low molecular weight antioxidant that works in conjunction with glutathione and other cellular antioxidants, and is effective against a variety of reactive oxygen species, including superoxide and hydroxyl radicals that have been implicated in the etiology of noise-induced hearing loss (NIHL). Whereas most animals can manufacture their own vitamin C, humans and a few other mammals such as guinea pigs lack the terminal enzyme for vitamin C synthesis and must obtain it from dietary sources. To determine if susceptibility to NIHL could be influenced by manipulating dietary levels of vitamin C, albino guinea pigs were raised for 35 days on a diet with normal, supplemented or deficient levels of ascorbate, then exposed to 4 kHz octave band noise at 114 dB SPL for 6 h to induce permanent threshold shifts (PTS) of the scalp-recorded auditory brainstem response. Animals that received the highest levels of dietary ascorbate developed significantly less PTS for click stimuli and 4, 8, 12, and 16 kHz tones than animals on normal and deficient diets. Outer hair cell loss was minimal in all groups after noise exposure, but permanent damage to stereocilia were observed in noise-exposed ears. The results support the hypothesis that dietary factors influence individual susceptibility to hearing loss, and suggest that high levels of vitamin C may be beneficial in reducing susceptibility to NIHL.

Acoustic Stimulation↗

[Age and features of cortical auditory evoked potentials].

Auditory evoked potentials (AEP) elicited by acoustic stimuli of various frequencies and intensities were studied in children aged from three to sixteen years. With age, peak latencies of the AEP components decrease on the average (taking into account the differences of such changes depending on the frequency and intensity of the stimuli presented) by 67.6 +/- +/- 13; 82.0 +/- 7.5; 65.6 +/- 7.2; 32.3 +/- 6.7 ms for components P1, N1, P2, N2 respectively. In 90% of the cases the thresholds of auditory sensations coincided with AEP thresholds; in 10% of the cases the thresholds of electrocortical reactions were by 5 dB lower than those of the auditory sensations. Enhancement of the stimulus to 80 dB lead to an increase of the AEP amplitude, while further augmentation of stimulus intensity in most cases resulted in a decrease of the AEP amplitude which was accompanied by unpleasant sensations or preceded their appearance. The frequency of this phenomenon drops with the age from 90% in 3-4 years old children, down to 30% in juveniles 15-16 years old.

Adolescent↗

Long-term effects of carboplatin brainstem infusions on hearing thresholds in monkeys.

OBJECTIVE: To isolate the central auditory neurotoxicity of carboplatin from its well-established ototoxic effects. DESIGN: The "best-case scenario" of targeted drug delivery to brain cancer was simulated by infusing carboplatin directly into the brainstem of cynomolgus monkeys with chronically implanted catheters. Because this manner of drug administration produced low levels of carboplatin in spinal fluid and blood, it was assumed that resulting deficits were dictated by the central auditory neurotoxicity of platinum compounds and not peripheral ototoxic effects. The magnitude of this hearing loss was estimated by comparing the auditory brainstem response thresholds of treated monkeys with results from normal controls. SUBJECTS: Six adult male cynomolgus monkeys (Macaca fascicularis) weighing 4 to 6 kg (3 received carboplatin treatment and 3 served as normal controls). INTERVENTION: Brainstem infusions of carboplatin. RESULTS: The average threshold of carboplatin-treated monkeys was elevated 8.8 dB (SD = 7.3 dB) relative to normal controls 6 months after the termination of drug delivery and increased to 10.7 dB with less variation between subjects (SD = 5.6 dB) 1 year after drug treatment. Although small in magnitude, the hearing loss was statistically significant (P<.05). CONCLUSIONS: Brainstem infusions of carboplatin induced some degree of hearing impairment in all treated monkeys. These threshold elevations were modest compared with the ototoxic effects that have been reported after systemic doses of carboplatin. Our findings suggest that the neurotoxic sensitivity of cochlear hair cells is not shared by neurons in the central auditory pathways. As a result, methods for reducing the ototoxic effects of chemotherapy remain a viable strategy for preserving auditory function in patients with brain cancer.

Animals↗

Pseudoauditory air conduction thresholds in the deaf.

Pure-tone air conduction thresholds, as well as speech detection thresholds, were obtained from both ears of 10 profoundly deaf individuals before and after the administration of a local anesthetic in two conditions: under earphones, and while wearing a conventional-type hearing aid. The results indicated only minimal differences between the pre-anesthetic and post-anesthetic thresholds. These findings support the contention that high intensity, low frequency thresholds in the profoundly deaf are primarily auditory in nature and do not contain significant vibratory components. The continued use of hearing aids with profoundly deaf children is recommended.

Adolescent↗

Correlation between electrical auditory brainstem response and perceptual thresholds in Digisonic cochlear implant users.

OBJECTIVES: To examine the relationships between psychophysical perceptions and the electrically evoked auditory brainstem responses (EABRs) in multichannel cochlear implant (CI) users and to determine the effectiveness of EABRs in electrode failure. DESIGN: A descriptive study reported the EABR characteristics while the different electrodes were activated. Characteristics of the EABR and of the perceptual measures served as compared variables in a correlational study. SETTING: The study was carried out in the audiology clinic of an otolaryngology department at a university hospital. PATIENTS: The subjects consisted of nine consecutively selected habitual Digisonic DX1OR multichannel CI users. Seven patients were postlinguistically deafened adult patients; two were congenitally deaf children. MAIN OUTCOME MEASURES: Ipsilateral recordings were performed using a previously published method. Morphology, latency, and amplitude measures of the EABR recordings were described, computed, and compared with the literature data for EABRs obtained while activating other types of CI and for acoustically evoked ABRs. Correlations between EABRs and behavioral perception thresholds were analyzed using the parametric Pearson's correlation test. RESULTS: EABRs allowed the authors to detect failure of no. 10 electrode integrity in one child. Perceptual threshold measures were found to be highly significantly related to the EABR threshold across subjects and electrode position (n = 31, r = 0.98; P < 0.001; linear regression equation: perceptual threshold = 1.06 EABR threshold + 0.76). The latencies and amplitudes were found to be similar to those described in the literature. CONCLUSIONS: EABRs may be used to estimate settings for the Digisonic DX10 CI even in a pediatric population, although they cannot entirely replace behavioral measurements, especially in children. The EABR can be employed for electrode dysfunction diagnosis. Further studies are needed to determine whether recordings of EABR quality could contribute to the evaluation of functional prognosis during the rehabilitation.

Adult↗