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Identification and separation of acoustic frequency following responses (FFRS) in man.

Frequency following responses (FFRs) to monaural tone bursts were recorded in normal and hearing impaired subjects as the potential difference between an ipsilateral earlobe electrode and a scalp vertex electrode. Whenn the rubber tube coupler between the earphone and the subject's ear was clamped, a stimulus artefact FFR was occasionally recorded. The "biological" FFR had a latency of about 1 msec and an irregular wave form which was made more sinusoidal by the addition of white noise. When the responses to tone bursts of opposite onset phases were added together, a "double frequency" FFR was obtained which had a latency of about 6 msec and whose amplitude was appreciably reduced by white noise. In some hearing impaired subjects (with no neural responses to clicks), this longer latency double frequency component could not be recorded, while in those cases in which the cochlear microphonic potential could be recorded, the shorter latency FFR was also present. It is concluded that the FFR in normally hearing subjects is made up of a short latency cochlear microphonic component and a longer latency neural component.

Adolescent

Usher's syndrome: electrophysiological tests of the visual and auditory systems.

The symptoms of Usher's syndrome - congenital hearing impairment and tapetoretinal dystrophy - are difficult to detect in young children. The electroretinogram (ERG), visual evoked potential (VEP), auditory nerve and brain-stem responses as well as the cochlear microphonic potentials were used to evaluate the defects of the visual and auditory systems in 20 patients, 3-45 years of age. This study demonstrates the usefulness, reliability and convenience of the electrophysiological tests for early diagnosis and functional evaluation of Usher's syndrome.

Adolescent

Bioelectric phenomena in the ototoxicity of nitrogen mustard.

The effects of nitrogen mustard on the electrical potentials of the inner ear were studied, and the results were correlated with the histopathologic findings which have been reported in nitrogen mustard ototoxicity. The endocochlear DC potential (EP) decreased rapidly after an injection of nitrogen mustard (NM). The amplitude of the cochlear microphonics potential (CM) diminished rapidly, and no substantial recoveries were observed. No significant changes in the magnitude of the negative potential of organ of Corti (NPOC) were observed. A large negative summating potential (SP) was recorded even when the amplitude of the CM had diminished.

Acoustic Stimulation

Vestibular microphonic potentials in pigeons.

Electrical responses to acoustic stimuli were measured by placing thin wire electrodes in the vestibular system of a pigeon model. Responses were measured after extirpation of the cochlea and the application of tetrodotoxin to the perilymphatic space. Responses seen were comparable to those of known cochlear microphonic potentials. These findings indicate that acoustic stimuli can evoke microphonic potentials in the vestibular system of the pigeon. We also found that vibrational amplitudes of less than 1 nm were sufficient to evoke a vestibular microphonic potential.

Acoustic Stimulation

Changes in cochlear microphonic sensitivity after priming C57BL/6j mice at various ages for audiogenic seizures.

Groups of mice were briefly exposed to a one-octave band of noise at 14, 18, 28, 38, or 58 days of age. Five days later the groups were divided, and some mice were behaviorally tested for audiogenic seizures by reexposing them to the same sound. The round window cochlear microphonic potential was measured in the remaining animals and compared with that observed in unprimed control subjects. Seizure behavior occurred in all animals primed on Day 18 but rarely for subjects in the other age groups. Cochlear microphonic threshold curves in mice primed on Day 18 showed a 30-dB loss in sensitivity, while all other primed groups showed little change. These data were discussed in terms of the "disuse-supersensitivity" hypothesis previously proposed to account for the physiological effects of priming in mice.

Acoustic Stimulation

Comparison of hearing threshold determined by auditory pathway electric responses and by behavioural responses.

In order to evaluate their reliability for determing the hearing threshold, the cochlear microphonic potentials, the auditory nerve and brain stem neural evoked responses as well as the cortical evoked responses were compared with the behavioural hearing thresholds of the same subjects in the same session. The threshold for recording the cochlear microphonic potnetial was found to be appreciably higher than the behavioral threshold. The threshold for recording the auditory nerve and brain stem responses was within a few decibels of the behavioural threshold. The thresold of the cortical evoked response was several decibels higher. It is concluded that (1) the auditory nerve and brain stem neural evoked responses are the best indicators of hearing threshold; (2) the cortical evoked responses are usually comparable, and (3) all types of evoked responses are indispensable aids in the evaluation of hearing and the determination of site of lesion in the auditory system.

Audiometry

Modulation of the masking phenomenon by the crossed part of the medial olivocochlear bundle.

The masking phenomenon is used in clinical investigation of the inner ear to determine the frequency selectivity properties of the auditory system. Sectioning of the crossed part of the medial efferent bundle in a guinea pig model decreases the simultaneous masking phenomenon. The efferent effect seen in the forward masking varied with the masking paradigm used. When the masker onset precedes the maskee onset by more than 40 ms, masking diminishes after sectioning the crossed part of the medial efferent bundle. When this duration was shortest (30 ms), no effect was observed. This phenomenon could be explained by the time necessary to stimulate the medial efferent loop. Our results could explain some differences observed in the compound action potential masking curves with different masking paradigms.

Acoustic Stimulation

[Correlation of the latency shift and brain stem potentials in basocochlear hearing loss and the time course of the click stimulus-induced evoked wave in the cochlea].

Frequency-specific information on high tone loss in the inner ear can, and if so only indirectly, be obtained from changes in latency of the click-evoked brain stem potential (ABR). The relationship between latency increases of the Jewett-wave-V in basocochlear hearing loss and the time course of the travelling wave on the basilar membrane will be presented. The latency increases of basocochlear hearing loss at 2 kHz, 1 kHz and 500 Hz correspond to both the computer-simulated time course of the travelling wave and to those of the derived responses. From a pathophysiological standpoint, receptor cells in basocochlear hearing loss are not functional, beginning at the oval window, so that, dependent on the degree of inactivity, a delay corresponding to that of the time course of the travelling wave passes until active hair cells are reached and action potentials released that produce, when summed up a potential of delayed latency.

Acoustic Stimulation

Blockade of synaptic transmission from hair cells to auditory afferent nerves by 6-cyano-2,3-dihydroxy-7-nitroquinoxaline, a selective non-NMDA receptor antagonist.

6-Cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) is a new, potent and selective competitive antagonist for the non-N-methyl-D-aspartate (non-NMDA) type of excitatory amino acids receptors. We studied the effect of CNQX on the compound auditory nerve action potential (CAP), cochlear microphonics (CM), summating potential (SP) and endocochlear potential (EP). CNQX in doses of 10-20 microM reduced the CAP magnitude and increased the N1 latency without affecting the CM, SP, or EP. Parallel shifts of CAP amplitude- and latency-intensity functions were observed. The CAP suppressed by 10 microM CNQX was completely reversed by a 10-min washout with artificial perilymph. As 10 microM and 20 microM CNQX seem to exert a selective antagonism for non-NMDA receptors, results indicate that non-NMDA receptors play a major role in synaptic transmission from hair cells to auditory afferent nerves.

6-Cyano-7-nitroquinoxaline-2,3-dione

A correlation of the effects of normoxia, hyperoxia and anoxia on PO2 of endolymph and cochlear potentials.

Change in PO2 in endolymph, endocochlear potentials and cochlear microphonics have been tested in normoxia, hyperoxia and anoxia on 24 guinea pigs. The polarographic method and construction of oxygen-sensitive microelectrodes is described in detail. The normal level of PO2 in endolymph vaires between 20 and 30 mm Hg. One-minute anoxia induced by breathing 100% N2 caused a decline in PO2, EP and CM, but during recovery only PO2 returned with over-correction to the preexposure level. Hyperoxia evoked by breathing 100% oxygen failed to increase the cochlear potentials and the PO2 in the endolymph. This suggests that vasoconstriction most likely occurs proximal to the capillaries bed of the stria vascularis.

Animals

Components of the frequency-following potential in man.

The scalp recorded frequency-following potentials (FFP) are a composite of several FFP's which may be distinguished by comparing simultaneously recorded waveforms from vertical and horizontal derivations in response to tones of very low frequently (below 350 Hz). The two most prominent FFP's were designated FFP1 and FFP2. FFP1 was recorded equally well in vertical and horizontal derivations and at a high stimulus intensities tended to be the predominant FFP. FFP2 followed FFP1 usually by about 1.7 msec and was optimally recorded in the vertical derivation. FFP2 threshold was about 10 dB lower than threshold for FFP1 and in several subjects, FFP2 was observed at 25 dB SL. Two other FFP's, a far-field recorded cochlear microphonic potential and a low-amplitude FFP, the latter presumably of neural origin, were also studied.

Acoustic Stimulation

Cochlear threshold assessment using tone-derived action potentials.

An evoked-potential technique has been evaluated which detects whether the cochlea responds to a continuous, low level tone. The technique involves recording the cochlear action potential (AP) response to a suprathreshold probe tone, first in the absence and then in the presence of a continuous masking tone at the same frequency. Subtraction of the masked AP waveform from the unmasked AP yields a 'derived' potential, provided the continuous tone is above the threshold of cochlear sensitivity. Derived AP responses may be recorded with continuous masking tones over 10 dB below the threshold to the probe stimulus. In normally hearing guinea pigs, the mean best derived threshold using a 10-microV response criterion was 7.1 dB SPL, compared to 18.9 dB for conventional AP thresholds. The tone-derived response appears to provide a more sensitive and frequency-specific method for determining cochlear thresholds.

Animals

Auditory brain stem responses in preterm infants: evidence of peripheral maturity.

This study explored further the relationship between peripheral and central auditory maturation on the basis of the auditory brain stem response. Auditory brain stem responses were recorded in preterm infants and adults to rarefaction and condensation click stimuli transduced through insert Tubephones. Infant recordings presented a triphasic waveform preceding wave I similar to that of the cochlear receptor potentials seen with adults during electrocochleography. Wave I latency and amplitude were found to be equivalent to those of adult subjects. Moreover, neither latency nor amplitude variability among infant wave I responses was found to be any greater than adults. Latencies of waves III and V, however, exhibited the expected differences relative to the adult comparison group. When the indirect evidence of cochlear receptor potentials in the infant are viewed adjacent to the observations that their ABR wave I latency, amplitude, and variability were entirely consistent with those of young adults, the data lend strong support for peripheral auditory electromaturity. These data are discussed relative to previously published reports of prolonged wave I latency in the infant which was attributed either to middle ear effects or immaturity of the cochlea and first order VIIIth nerve neurons.

Adult

Modulation of cochlear tuning by low-frequency sound.

An intense, low-frequency tone (about 30 Hz) modulates the sensitivity of the inner ear to high-frequency stimulation. This modulation is correlated with the displacement of the basilar membrane. The findings suggest that the modulation may also affect cochlear tuning. We have investigated modulation of cochlear tuning by low-frequency sound in the guinea pig. Applying indirect methods of measurement (narrow-band analysis of compound action potentials and compound-action-potential tuning curves), the results suggest a shift of the excitation pattern along the basilar membrane towards higher-frequency areas. The shift occurred for both scala tympani and scala vestibuli displacement of the cochlear partition. Tuning curves, obtained from single units in the cochlear nerve, show sensitivity loss and a tip shift towards lower frequencies. This was also found for both scala tympani displacement and scala vestibuli displacement. The shift of the tip of the tuning curve towards lower frequencies corresponds to the inferred high-frequency shift of the excitation pattern. The relationship of these phenomena with the pathophysiology of Ménière's disease and with possible active mechanisms in cochlear transduction is discussed.

Animals

The combined effect of cisplatin and furosemide on hearing function in guinea pigs.

The effect of the combined administration of cisplatin and furosemide on the electrophysiological hearing thresholds and endocochlear DC potential (EP) was studied in guinea pigs. A lack of interaction was found in animals given repeated intraperitoneal injections of a low dose of cisplatin with a pharmacological dose of furosemide. An ototoxic interaction occurred when a moderately high dose of cisplatin was administered intravenously at a time when the strial function was most affected by a very high dose of furosemide. The interaction was seen both as a decreased EP and a pronounced shift of auditory thresholds. It is concluded that the stria vascularis plays a role in the ototoxic mechanism of cisplatin.

Animals

Thresholds of cat cochlear nucleus neurons to microwave pulses.

Action potentials of neurons in cat dorsal and posteroventral cochlear nuclei were recorded extracellularly with glass microelectrodes while the head of the cat was exposed to microwave pulses at 915 MHz using a diathermy applicator. Response thresholds to acoustic tones, acoustic clicks, and microwave pulses were determined for auditory units with characteristic frequencies (CFs) from 278 Hz to 39.2 kHz. Tests with pulsatile stimuli were performed for durations of 20-700 mus, principally 20, 70, and 200 mus. Brainstem midline specific absorption rate (SAR) threshold was as small as 11.1 mW/g per pulse, and specific absorption (SA) threshold was a small as 0.6 muJ/g per pulse. Microwave thresholds were generally lower for CF less than 9 kHz, as were most acoustic thresholds. However, microwave threshold was only weakly related to click threshold and CF-tone threshold of each unit.

Animals

Rapid disruption of cochlear function and structure by trimethyltin in the guinea pig.

Trimethyltin (TMT) is a potent ototoxicant which acutely disrupts generation of the action potential evoked by a broad range of tone frequencies and subsequently produces selective high frequency impairment and outer hair cell (OHC) damage in the extreme basal turn of the cochlea. We investigated the development of TMT ototoxicity in the guinea pig 6-48 h following treatment using the compound action potential (CAP), cochlear microphonic (CM), endocochlear potential (EP) and light and electron microscopic examinations. At all time intervals studied, TMT reduced CAP sensitivity and CM amplitude. The effect was relatively broad across test frequencies at 6 h and subsequently became restricted to higher frequencies. No disruption of the EP was observed between 6 and 24 h following TMT. OHC pathology in the basal turn of the cochlea 12 h following TMT consisted of vacuolization in the supranuclear region and disruption of the cuticular plate; some mitochondria exhibited dark inclusions. Type 1 spiral ganglion cells appeared swollen at 24 h with separation of myelin from the cell bodies. No pathological changes were observed in the inner hair cells (IHC). The present data identify the OHC as targets responsible for the loss of CM sensitivity after TMT as the EP was unaffected. These data suggest that CAP and CM recovery at low and middle frequencies following acute TMT administration is accompanied by recovery of neurotransmission at the IHC or Type 1 SGC level and OHC recovery at apical regions of the cochlea.

Action Potentials

Electrically evoked whole-nerve action potentials: data from human cochlear implant users.

This study describes a method for recording the electrically evoked, whole-nerve action potential (EAP) in users of the Ineraid cochlear implant. The method is an adaptation of one originally used by Charlet de Sauvage et al. [J. Acoust. Soc. Am. 73, 615-627 (1983)] in guinea pigs. The response, recorded from 11 subjects, consists of a single negative peak that occurs with a latency of approximately 0.4 ms. EAP input/output functions are steeply sloping and monotonic. Response amplitudes ranging up to 160 micro V have been recorded. Slope of the EAP input/output function correlates modestly (approximately 0.6-0.69) with results of tests measuring word recognition skills. The refractory properties of the auditory nerve were also assessed. Differences across subjects were found in the rate of recovery from the refractory state. These findings imply that there may be difference across subjects in the accuracy with which rapid temporal cues can be coded at the level of the auditory nerve. Reasonably strong correlations (approximately 0.74-0.85) have been found between the magnitude of the slope of these recovery curves and performance on tests of word recognition.

Cochlear Implants