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Auditory evoked responses under total spinal anesthesia in rats.

In order to investigate the function of the auditory pathway from the cochlea to the brain stem under total spinal anesthesia, the auditory brain stem response (ABR), compound action potential of the cochlear nerve (CAP), and cochlear microphonics (CM) were simultaneously recorded in rats. Total spinal anesthesia was induced by infusion of 2% lidocaine hydrochloride at a constant rate of 0.10 mL/min into the cerebrospinal fluid through the rats' skulls. The ABR completely disappeared within 1.5 to 4 minutes. After cessation of the injection, the ABR reappeared, starting from wave I and progressing through waves II and III to wave IV. The latency change of the CAP throughout the recording period was quite similar to that of wave I of the ABR. A reduction in amplitude of the CM was observed, but the CM did not disappear during the recording period. Disappearance of the ABR was due, not to loss of cochlear function, but to anesthetic effects on the acoustic nerve and the brain stem. Monitoring of the ABR provided information on the level of neural activity in the brain stem under total spinal anesthesia.

Action Potentials↗

Distortion-product otoacoustic emissions and cochlear microphonics: relationships in patients with and without endolymphatic hydrops.

OBJECTIVES: Because endolymphatic hydrops causes cochlear malfunction, and both otoacoustic emissions and cochlear microphonics measure specific cochlear activities, some insight into the pathology of Meniere's disease might be gained by using these two test modalities. Specifically, the involvement of cochlear outer hair cells in patients with endolymphatic hydrops may be detected. Furthermore, it is hoped that these two tests might help determine which regions of the cochlea are affected by endolymphatic hydrops, as well as where along the auditory pathway abnormalities are present. STUDY DESIGN: Data were gathered prospectively on patients presenting to a private, tertiary referral otology/neurotology practice. METHODS: From February 1999 to April 2000, clinical information was collected on patients presenting with vertigo, hearing loss (HL), sudden HL, fluctuant HL, aural fullness, and/or tinnitus. Data included demographics, diagnosis, pure-tone and speech audiometry, tympanometry, summating potential, action potential, cochlear microphonic, and distortion-product otoacoustic emissions. Descriptive statistics were calculated, and relationships between distortion-product otoacoustic emissions and cochlear microphonics in patients with hydrops (defined as summating potential to action potential ratio > or =0.40) and without hydrops were analyzed. RESULTS: Distortion-product otoacoustic emissions were present more often and had larger amplitudes at the lower frequencies. No differences were found in the presence of distortion-product otoacoustic emissions across the frequencies for the two groups, but larger mean amplitudes were found for hydropic ears at 7966 Hz. As hearing levels worsened, both hydropic and nonhydropic ears were less likely to have emissions present; however, 18% of hydropic ears had emissions unexpectedly present when the pure-tone thresholds were > or =50 dB. The cochlear microphonic from the hydrops group tended to be smaller, but this was not statistically significant. Analysis of variance showed a small negative correlation between summating potential to action potential ratio and level of emission at 1968 Hz in hydropic ears; otherwise, there was no relationship between the ratio and emissions. The only statistically significant finding when analyzing the relationship between cochlear microphonic and otoacoustic emission was a small positive correlation between level of microphonic and level of emission at 1406 Hz in hydropic ears. No significant relationships were found between hearing thresholds and emissions or microphonics. CONCLUSIONS: Even though both distortion-product otoacoustic emissions (DPOAEs) and cochlear microphonics (CMs) measure specific cochlear activities, they were not found to be useful for differentiating patients with hydrops from those without. In some patients, however, unexpected distortion-product otoacoustic emissions were present. This may represent localizing information about which regions of the cochlea are being affected by hydrops in these patients. Also, a small positive correlation between the CM and the DPOAE at 1406 Hz was detected in the hydrops group, which may represent the effects of endolymphatic hydrops on the outer hair cell. Future investigations involving hydropic patients with unexpected DPOAEs and studies looking for more DPOAE and CM correlations at frequencies surrounding 1406 Hz are being planned.

Adult↗

Loud sound-induced changes in cochlear mechanics.

To investigate the inner ear response to intense sound and the mechanisms behind temporary threshold shifts, anesthetized guinea pigs were exposed to tones at 100-112 dB SPL. Basilar membrane vibration was measured using laser velocimetry, and the cochlear microphonic potential, compound action potential of the auditory nerve, and local electric AC potentials in the organ of Corti were used as additional indicators of cochlear function. After exposure to a 12-kHz intense tone, basilar membrane vibrations in response to probe tones at the characteristic frequency of the recording location (17 kHz) were transiently reduced. This reduction recovered over the course of 50 ms in most cases. Organ of Corti AC potentials were also reduced and recovered with a time course similar to the basilar membrane. When using a probe tone at either 1 or 4 kHz, organ of Corti AC potentials were unaffected by loud sound, indicating that transducer channels remained intact. In most experiments, both the basilar membrane and the cochlear microphonic response to the 12-kHz overstimulation was constant throughout the duration of the intense stimulus, despite a large loss of cochlear sensitivity. It is concluded that the reduction of basilar membrane velocity that followed loud sound was caused by changes in cochlear amplification and that the cochlear response to intense stimulation is determined by the passive mechanical properties of the inner ear structures.

Acoustic Stimulation↗

[Effect of hypoxia at 5% oxygen on global electrophysiological responses from normal awake guinea pigs].

All experiments were conducted on awake guinea pigs warranting a normal physiological function of the circulatory system. Global electrophysiological responses from the round window of cochlea were monitored: cochlear microphonic (CM), summating potential (SP) and auditory compound action potential (AP). The results showed that hypoxia induced a threshold elevation at all frequencies thus affecting the whole cochlea, and also very large diminutions of AP at high intensity level exclusively in response to a high frequency, and very large increases of SP at 2 kHz and 8 kHz. After hypoxia, which lasted thirty minutes, a considerable recovery occurred, and at the end of the session recovery reached around eighty percent. Alterations of cochlea action potential in response to high intensity stimuli were dissociated from threshold changes. We speculate that threshold elevation could be associated with over-all energetic (ATP) decrease leading to diminution of endolymphatic resting potential. Action potential changes at high intensity and at cochlear base could reflect neurotransmission (afferent, efferent or sympathetic) disturbance.

Action Potentials↗

Selective inner hair cell loss does not alter distortion product otoacoustic emissions.

Outer hair cells (OHC) are believed to be the dominant source of distortion product otoacoustic emissions (DPOAE) in mammals; however, some studies in genetic mutants suggest that inner hair cell (IHC) loss may lead to a significant reduction of DPOAE amplitude. In the present study, we determined the extent to which IHC loss altered DPOAE amplitude by using carboplatin to destroy selectively the IHCs in the chinchilla while sparing virtually all of the OHCs. IHC losses of 80-100% with normal retention of OHCs did not reduce the amplitude of the DPOAEs or the cochlear microphonic potential (CM); however, it completely abolished the compound action potential (CAP). The only time that the amplitude of the DPOAEs and CM were reduced was in cases where both the IHCs and OHCs were destroyed in the base of the cochlea. We conclude that the total loss of IHCs does not lead to a significant change in DPOAE amplitude. DPOAE amplitude was only reduced when there was a significant loss of OHCs.

Action Potentials↗

The effect of cervical sympathectomy on cochlear electrophysiology.

The purpose of this study was to examine the electrophysiologic responses to sound from guinea pig cochleas, 3--6 days after a unilateral cervical sympathectomy. After recovery from surgery the guinea pigs developed a Horner's syndrome on the sympathectomized side. Some days later their bullas were opened and electrodes were placed bilaterally on the round windows. Most of the sympathectomized cochleas showed signs of decreased sensitivity to sound. They had a smaller dynamic range for the click- and tone-burst evoked compound action potential (CAP) compared with the non-sympathectomized cochleas. The threshold sound levels for the CAPs and the sound levels to produce 1 muV of cochlear microphonic potentials were unaffected. In other animals with chronic implanted electrodes, the same electrical responses were measured with only light sedation before and after sympathectomy and showed the same results. In additional animals the crossed olivocochlear bundle (COCB) was electrically stimulated and a similar inhibition of the CAP was registered on both the intact and the sympathectomized side. The results suggest that the sympathetic nerves to the cochlea, coming from the ipsilateral cervical ganglion and ending near the habenula perforata, may be important for the sound perception as they influence the CAP.

Action Potentials↗

Electrophysiological evidence for the presence of NMDA receptors in the guinea pig cochlea.

An excitatory amino acid, possibly L-glutamate, which probably acts as a neurotransmitter at the inner hair cell-afferent fiber synapses in the cochlea. In the present study, we have used an electrophysiological approach to investigate at this level the presence of a major type of excitatory amino acid receptor, namely the glutamatergic receptor for which N-methyl-D-aspartate is a selective agonist. Our results show that, when N-methyl-D-aspartate and the antagonist 2-amino-5-phosphonovalerate are perfused through the perilymphatic scalae, they induced, by different mechanisms, a significant reduction of the amplitude of the compound action potential and an increase of the N1 latency, both predominant at high intensity tone burst stimulations. No significant difference was found in the presence or absence of Mg2+ in the artificial perilymph used as a vehicle. A further slight N-methyl-D-aspartate-induced decrease of the amplitude of the compound action potential, although non significant, was observed when the Mg2(+)-free perilymph contained 100 or 1000 microM glycine. In all the experimental conditions, no effect was observed on the cochlear microphonic potential. This observation is consistent with an action of N-methyl-D-aspartate and 2-amino-5-phosphonovalerate at receptors located on the auditory nerve dendrites contacting the inner hair cells. In conclusion, our results suggest the presence of N-methyl-D-aspartate receptors in the cochlea.

2-Amino-5-phosphonovalerate↗

An energy-dependent step in aminoglycoside ototoxicity: prevention of gentamicin ototoxicity during reduced endolymphatic potential.

Guinea pigs received a bolus of gentamicin (10 mM for 5 min) by perilymphatic perfusion which normally led to an irreversible loss of the cochlear microphonic potential (CM). Various experimental conditions that reduced the endolymphatic potential (EP) were then superimposed on the gentamicin application. Reversible reductions in EP (and, concomitantly, in CM) were induced by asphyxia (3 min), intravenous furosemide (50 mg/kg), and perilymphatic perfusion of aminooxyacetic acid (10 mM). When the administration of gentamicin was initiated at the time of maximal EP reduction the usual irreversible gentamicin-induced decline of CM was prevented. The results indicate that a metabolic process is essential in the expression of gentamicin toxicity. The data are consistent with the inhibition of an energy-dependent transport of the aminoglycoside. Alternatively, the data are also compatible with the hypothesis that entry of gentamicin into hair cells is prevented by a reduction in their transmembrane electrical potential.

Aminoglycosides↗

[Animal experiment studies using a low-frequency, phase-delayed masker in inner ear diagnosis].

Endolymphatic hydrops is usually diagnosed on the basis of clinical symptoms although objective parameters for this disease can be difficult to differentiate from other disorders of the inner ear. Low-frequency acoustic biasing using a highly intensive phase-shifted low-frequency masker was studied according to its ability to determine disorders of cochlear micromechanics in diseases caused in animal models. Ossicular disruption, experimentally induced early endolymphatic hydrops and gentamycin-induced inner ear damage could be objectively determined histologically and electrophysiologically. Statistical analysis proved that the low-frequency acoustic biasing technique allowed electrophysiologic differentiation of the groups studied that was independent from known clinical parameters. To substantiate the group differences by variance analysis, an intensity of at least 100 dB SPL was required for the 52 Hz masker, and the difference in relation to the test-tone intensity had to be 10 or 20 dB SPL. The early stages of experimentally-induced endolymphatic hydrops could be identified by means of a low-distinct modulation span of the compound action potential amplitude (< 50 uV) and a reduced positive summating potential amplitude with a phase-shifted maximum value compared to the control groups. During the test phases the cochlear microphonic potentials showed only slight suppression of their amplitudes and no modulation effect when compared to the control groups. The modulation behavior of the responses could be correlated with the histologic and supposed micromechanic states of the basilar membrane and organ of Corti, thus allowing validation of the measuring technique.

Animals↗

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid electrophysiological and neurotoxic effects in the guinea-pig cochlea.

We have recorded cochlear potentials after perilymphatic perfusion of cumulative doses of the excitatory amino acid alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) which selectively recognizes the non-N-methyl-D-aspartate ionotropic receptor formerly known as the quisqualate receptor. Our results show that AMPA (1-80 microM) caused a significant suppression of the amplitude of the compound action potential evoked by acoustic stimulation. A total elimination of this potential at the 100 microM concentration was observed in all animals. In no case was the cochlear microphonic potential, a hair cell receptor potential, affected by AMPA. Histological examinations were performed either at the end of the physiological studies or on cochleas perfused for 10 min with a single dose of AMPA (50 or 100 microM). In both experimental conditions, a selective dendritic swelling or radial afferent nerve endings under the sensory inner hair cells was observed. No damage was found in both types of hair cells supporting cells, lateral and medial efferent fibers and spiral afferent nerve ending on the outer hair cells. The occurrence of the radial dendrite swelling was prevented when 6,7-dinitroquinoxaline-2,3-dione (500 microM) was perfused in the cochlea 10 min prior, then concomitantly with AMPA. The present study strongly suggests that non-N-methyl-D-aspartate receptors, possibly of the AMPA subtype, are involved in the synaptic transmission between the inner hair cells and the primary auditory neurons. They provide further support for the hypothesis that L-glutamate, or another excitatory amino acid, acts as an inner hair cell neurotransmitter.

Acoustic Stimulation↗

Intracochlear acoustic pressure measurements: transfer functions of the middle ear and cochlear mechanics.

Direct intracochlear acoustic pressure recordings (from 20 to 20,000 Hz) are used to measure the middle-ear transfer functions (forward and reverse) and to better understand the cochlear mechanics in the guinea pig. In the forward direction, the middle-ear transfer function is strongly dependent on the frequency and presents a maximum of +30 dB at 1,000 Hz (bulla open). In the reverse direction, the middle-ear transfer function looks like an ideal reverse middle-ear pressure transformer with -35 dB gain and 0 degrees phase lag from 20 to 8,000 Hz (bulla open, closed ear canal). Passive cochlear mechanics is studied with the help of intracochlear pressure measurements and differential cochlear microphonic potential recordings in the different turns.

Acoustic Stimulation↗

Combined cochleo-saccular and neuroepithelial abnormalities in the Varitint-waddler-J (VaJ) mouse.

Hearing loss in Varitint-waddler-J (VaJ) mice is of mixed origin with both cochleo-saccular and neuroepithelial components. Both VaJ/VaJ and VaJ/+ mutants show impaired cochlear function, but the homozygotes are more severely affected than heterozygotes. Neither group have any detectable compound action potential. Cochlear microphonics are only seen in half of the heterozygotes, at a reduced amplitude and raised threshold, and are not detected in any homozygotes. Summating potentials (SP) responses are seen in most of the heterozygotes, at high stimulus levels. The only responses in homozygotes were negative SPs seen in half of the mutants at very high sound levels, while the remaining homozygotes showed no responses to sound stimulation. Endocochlear potentials (EP) were often small or absent in both groups of mutants, with the homozygotes being more severely affected. Reduced pigmentation in the stria vascularis appears to be associated with a reduced EP, while a primary defect of the neuroepithelium, detectable by electron microscopy in hair cells of 14 day old mice, dramatically influences evoked potentials.

Animals↗

Contributing generator of frequency-following response in man.

A contributing generator of the frequency-following response (FFR) was identified in a patient with severe neurological impairment, by comparing latencies and phase shifts of the FFR to the latency of the auditory brainstem evoked responses (ABR), and by comparing the duration of the FFR to that of the acoustic stimulus. In this patient, the ABR comprised only waves I and II; activity in the inferior colliculus was not identified. Both onset and offset latencies and phase shifts of the FFR were substantially shorter than the latency of the first wave of the ABR. The duration of the FFR corresponded precisely to that of the acoustic stimulus. These results are interpreted as supporting the view that the cochlear microphonic potential (CM) contributes to the scalp-recorded FFR.

Brain↗

The effects of ototoxicity on the auditory brain stem response and the scalp-recorded cochlear microphonic in guinea pigs.

The objective determination of hearing impairment with evoled response techniques may be of value in the early detection of ototoxic reactions, especially in infants and other "difficult" patient populations. In this study the auditory brain stem response to "clicks" at two intensities and two repetition rates were recorded from guinea pigs that had been given one of two dosage levels of kanamycin or no drug. The scalp-recorded cochlear microphonic to continuous tones was also recorded. Hearing loss was seen in one-third of the animals receiving kanamycin. The temporal course of the deficit varied considerably between animals. Auditory system change was most readily detected in response to low-intensity stimuli, while change in repetition rate of the clicks did not affect the results. The cochlear microphonic potentials correlated with the auditory brain stem response.

Animals↗

The influence of transient asphyxia on receptor potentials in inner hair cells of the guinea pig cochlea.

Intracellular recordings were made from inner hair cells in the basal turn of the guinea pig cochlea during transient asphyxia. During these periods the endocochlear potential was reversibly reduced, the hair cell resting membrane potential was slightly hyperpolarized and the cochlear microphonic potential was decreased, all with similar time courses. The eighth nerve compound action potential and DC and AC components of the inner hair cell receptor potential were strongly attenuated and with similar slow time courses. The asymmetrical low frequency receptor potentials became symmetrical, and this change was attributed to alterations in the mechanical properties of the organ of Corti. The desensitization of the cochlea during transient asphyxia was associated with the loss of asymmetry of the inner hair cell receptor potential.

Animals↗

The effect of sectioning auditory centrifugal fibers on the cochlear microphonic and action potential in guinea pigs.

This investigation on 8 guniea pigs determined the immediate effect on the cochlear microphonic (CM) and action potential (AP) of ipsilateral sectoning of the autitory centrifugal fibers. An acoustic signal was used to evoke the CM and AP of one ear of guinea pig and the homolateral olivo-cochlear bundle and lateral lemniscus were then sectioned. Differences between pre- and post-section CM and AP were measured. The results demonstrated an increase in the CM and a decrease in the AP in all animals. Speculation with regard to the overall function of the auditory centrifugal system was offered.

Action Potentials↗

Cochlear function and sodium and potassium activated adenosine triphosphatase.

The maintenance of the cation gradients between endolymph and perilymph in the cochlea requires the operation of a cation pump. An adenosine triphosphatase system activated by sodium and potassium is present in high activity in the cochlear membranes (tegmentum vasculosum and stria vascularis). The cochlear microphonic potential is inhibited by perilymphatic perfusion of ouabain and erythrophleine. Since the microphonic potential depends on the high concentration of potassium ions in the endolymph, our findings strongly suggest the operation of an adenosine triphosphatase cation pump system activated by sodium and potassium, in the generation of cochlear cation gradients.

Animals↗

Ménière's disease and the summating potential. III. Effect of glycerol administration.

We investigated the effect of administering hypertonic glycerol on cochlear and auditory nerve responses to rectangular-pulse clicks and on pure-tone behavioral thresholds. Eleven ears with Ménière's disease, and 20 ears without the disease were studied. Among the ears with Ménière's disease summating potential (SP) amplitudes decreased and 250 to 1,000-Hz thresholds improved after glycerol administration. Action potential amplitudes from the ears with Ménière's disease also decreased after glycerol ingestion, but to a lesser degree. In contrast, among the ears without Ménieère's disease, 250- to 1,000-Hz behavioral thresholds did not change significantly after glycerol nor did any of the electrophysiologic responses. Analogous group differences were found when the ears were regrouped according to the presence of absence of pathologic SP enlargement. These results demonstrate a tendency for three variables-(1) clinical diagnosis of Ménière's disease, (2) enlarged SP, and (3) positive glycerol test result-to cluster together in the same population of ears.

Action Potentials↗