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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

[The promontory test and electrocochleography with reference to indications for cochlear implant].

A successful cochlear implant demands a functioning auditory nerve. A subjective and qualitative recording can be obtained by promontory testing (PT) whereas cochlear microphonics (CM) give information about the status of the hair-cells in the inner ear. The results of both tests together show different patterns: in sensory deafness in which a cochlear implant is indicated, no CM and no compound action potentials (CAP) can be obtained, whereas the patient reports hearing sensations (PT positive) in response to promontory testing. Deafness caused by lesions close to the second neurone of the auditory pathways can be localized by preserved CM and CAP, but there is no response to promontory testing. A ganglionic deafness ie. of the first neurone can be distinguished by preserved CM, absent CAP and a negative PT. The combined results of electrocochleography and promontory testing help in deciding whether a cochlear implant is indicated, and in localising the origin of the deafness, eg. neural or sensorineural. The possible results are illustrated by examples.

Adult

[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

Origins of the scalp recorded frequency-following response in the cat.

The frequency-following response (FFR) is a short-latency scalp-recorded evoked potential elicited by the presentation of low-frequency acoustic stimuli. It is thought to be the result of the synchronous electrical activity in brain stemauditory nuclei to each wave in the acoustic signal. The present investigation constitutes an attempt to determine the generators of the FFR in the cat by analysis of the response and by section of brain stem auditory nuclei and tracts. Among the results were the following: (1) the cochlear nuclei contribute approximately 50% of the amplitude of the scalp-recordedFFR in the cat. (2) The cochlea also makes a significant contribution, accounting for an average of nearly 25% of the response amplitude. (3) The superior olivary nuclei (and/or the nuclei of the lateral lemnisci) account for about 20% of the response amplitude. (4) The contributions from the inferior colliculi (contrary to earlier studies) were found to be relatively insignificant. (5) As a consequence of the existence of multiple generators, the FFR ample area of hair cell excitation for each stimulus frequency involved in the mediation of the FFR, suggestion that scalp-recorded FFRs could be used to ascertain low-frequency hearingsensitivity in uncooperative human subjects.

Animals

Latency and amplitude tuning curves of the N1 and N2 components of the cochlear nerve compound action potential.

Compound action potential tuning curves (CAP TCs) generated by masking the N1 component of the CAP provide a means of assessing the ability of the cochlea to selectively tune to certain stimuli. This paper examines some of the factors which can influence this TC when a moderately intense (i.e. 40-80 dB SPL) probe stimulus is used. At these levels, each of the four corners of the trapezoidal stimulus envelope is capable of generating a CAP. Also, short stimulus rise times can merge the CAPs produced by the first two corners, but this does not appear to have a major effect on the CAP TC. It was shown that the N2 component of the CAP for the first corner of the stimulus is equally capable of producing a well-tuned TC. Another study has shown that, in addition to amplitude decrements, one can use latency increases as a criterion for CAP TCs. We have demonstrated that latency TCs are more finely tuned than amplitude TCs at high levels, especially when the stimulus rise time is short.

Animals

Compound action potential input/output functions in young and quiet-aged gerbils.

Auditory-nerve compound action potentials (CAP) and cochlear microphonic (CM) potentials were measured with round window electrodes in two sets of quiet-reared gerbils: young (N = 9 ears, 4-7 months) and aged (N = 11 ears, 35-37 months). CAP thresholds, measured at probe frequencies from 0.5 to 25.6 kHz, are plotted as audibility curves. Input/output (I/O) functions were derived from CAP and CM amplitude measurements at six frequencies. When compared to young controls, CAP audibility curves from aged animals all show some degree of threshold shift, ranging from minimal to severe, as well as increased variability. Our data suggest that some of the variability in the aged-animal audibility curves can be attributed to variations in individual genetic factors. Maximum CAP amplitudes for the aged animals average significantly less than those of the young controls at all frequencies tested. Young control I/O functions are generally steeper than those of the aged gerbils. Differences in the CM amplitudes of the young and aged gerbils are not as clear cut as the differences in the CAP. Possible mechanisms explaining the decrease in amplitudes and slopes of the CAP I/O functions in aged animals include changes in numbers or thresholds of primary ganglion cells, or a decrease in synchrony in discharges of auditory-nerve fibers.

Action Potentials

Offset AP masker tuning curve and the FFT of the stimulus.

In previous experiments, it was noted that a cochlear compound action potential (CAP) can be produced by the offset of a tone, provided that the amplitude of the tone is modulated by a trapezoid with slopes that are typically much steeper than required to produce onset responses. Subsequently, such trapezoidal tone bursts with steep slopes were used as probe stimuli in simultaneous and forward masking experiments that were designed to evaluate the tuning characteristics of these offset CAPs. Masker tuning curves (MTCs) were generated by plotting the masker frequency necessary to reduce the amplitude of the offset CAP by 50%. Simultaneous masking of the offset CAP generated a W-shaped MTC, with two sharply tuned tips and one sharply tuned peak. Forward masking generated a sharply tuned V-shaped offset MTC. By contrast, for onset CAPs, both simultaneous and forward masking generated V-shaped MTCs. The very steep stimulus slopes required to produce an offset CAP are likely to generate much more acoustic splatter than the more gradual slopes required to produce an onset CAP, and this may be related to the different shapes of the onset and offset simultaneous MTCs. To explore this possibility, the relationship of the spectral characteristics (determined by fast Fourier transform, or FFT) to the shape of the MTC was studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Cochlear action potential tuning curves recorded with a derived response technique.

Previous action potential (AP) tuning curve methods have used a reduction in amplitude of the probe-elicited AP as an indication of tone-induced masking. The reduction criterion used in different studies has varied from 25% to 100%. For low level probe stimuli, which elicit a low-amplitude AP, this is a sensitive indicator. In contrast, for high-amplitude AP responses elicited by high-level stimuli, the required reduction in absolute terms is large, making it an insensitive indicator. AP tuning curves have been recorded using a sensitive method for detecting masker/probe interaction with a fixed criterion, unrelated to the unmasked AP amplitude. For each masking condition, a derived response was obtained by digitally subtracting the tone-masked AP waveform from the unmasked response. Derived responses are generated if there are ANY changes in the AP waveform induced by the masker, including amplitude changes, latency changes, or even changes in AP morphology not necessarily associated with the major peaks. A fixed criterion (10 microV) of tone-derived (TD) response was used as an indication of interaction of the responses to the masker and probe. Tuning curves generated by this method were compared with those generated by conventional amplitude reduction (AR) methods. TD tuning curves show different characteristics, especially with respect to increasing probe levels. They appear to give a good representation of the array of afferent fibers responding to a probe stimulus. In addition, frequency regions making minor contributions to the AP are better represented in TD tuning curves.

Animals