Cochlear Action Potential Research Articles

PS-36-5 Intraoperative monitoring of cochlear nerve compound action potentials during acoustic neurinoma surgery for hearing preservation

PS-36-5 Intraoperative monitoring of cochlear nerve compound action potentials during acoustic neurinoma surgery for hearing preservation

Effects of acoustic overstimulation on cochlear evoked potentials.

Guinea pigs were exposed to 2 kHz pure-tone or octave-band pass noise at an intensity of 100 dBSPL for 30 min. The effects of sound exposure on cochlear microphonics (CM) and compound action potential (AP) were studied using a test condition devised to complete the measurement of the sensitivity of both potentials for the frequency from 1 to 7 kHz within several minutes. The loss of CM sensitivity was limited to around 5 dB for all test frequencies in animals exposed either to pure-tone or band noise. In contrast, the loss of AP in both exposure conditions was significantly greater than that of the CM, and the magnitude of the AP losses reflected the frequency characteristics of the exposure sounds. From these observations, the AP is considered to be a more sufficient index than the CM in studying the effects of acoustic overstimulation.

The effect of 6 kHz tone exposure on inner ear function of the guinea pig: relation to changes in cochlear microphonics, action potential, endocochlear potential and chemical potentials of K(+)-ions and Na(+)-ions, using a double-barrel glass electrode.

Using 97 male albino guinea pigs and applying electrophysiological methods, the effects of a 6 kHz tone were investigated at a moderate sound pressure level to the inner ear during a 24-h exposure time. Following exposure to the 6 kHz tone at 90 dB, cochleas showed decreased maximum output voltage of cochlear microphonics (CM) and action potential (AP). In the endolymph, K+ ion and Na+ ion concentrations remained unchanged during 40 min anoxia and 90 dB tone exposure. At 80 dB sound exposure decreases in maximum output voltage of CM and AP and decreases in the absolute value of EP could not be detected. Endolymph K(+)-ion Na(+)-ion concentrations were also unchanged. These findings indicate that diffusion potentials are induced at the same time as decreases of maximum output voltage in CM induced by exposure to sound at 90 dB.

Cochlear function after selective inner hair cell degeneration induced by carboplatin

The ototoxicity of carboplatin, a second generation anti-cancer agent, was examined using the chinchilla as an animal model. In animals treated with a clinical therapeutic dose (400 mg/m 2), the dominant degenerative change is to inner hair cells (IHCs). This is in sharp contrast to most other ototoxic agents, which damage primarily the outer hair cells (OHCs). Functional changes to the cochlea have been evaluated in carboplatin treated subjects by recording cochlear action potentials (CAP) and cochlear microphonics (CM); cochlear lesions were evaluated using scanning electron microscopy. In carboplatin treated animals, CAP thresholds to tone-pip stimuli were elevated in proportion to IHC damage in corresponding cochlear regions. In contrast, CM amplitudes and ‘thresholds’ remained close to normal in most cases, reflecting the preservation of OHCs in the basal turn. These results indicate a high degree of independence between the inner and outer hair cell systems in the cochlear transduction mechanism. We suggest that this species-specific preparation with selective IHC loss will provide a valuable tool for studying, separately, the role of OHCs in both afferent and efferent cochlear function.

Substance P increases cochlear blood flow without changing cochlear electrophysiology in rats

Carotid artery infusions of substance P yielded reductions in systemic blood pressure and elevations in cochlear blood flow (CoBF), measured via laser Doppler flowmeter, with no alterations in cochlear action potentials or cochlear microphonics in Wistar-Kyoto rats. Additionally, direct micro-infusions of substance P into the anterior inferior cerebellar artery, which contributes to the local vascular perfusion of the cochlea, yielded elevations in CoBF with no changes in systemic blood pressure. Pretreatment with a specific substance P receptor antagonist, ([D-Pro 2,D-Trp 7,9]SP) via the carotid artery or the anterior inferior cerebellar artery, diminished subsequent substance P-induced vascular responses. These results suggest that endogenous substance P, like other vasoactive peptides, may interact with a substance P-specific receptor population in the cochlea and may therefore participate in the ongoing regulation of CoBF. These findings also support the premise that vasodilatory hormones, along with vasoconstrictive agents, may be involved in the autoregulation of CoBF.

Role of thromboxane A2 in a microcirculation disorder of the rat inner ear.

Since thromboxane (TX) A2 causes vasoconstriction and platelet aggregation, we evaluation the effect of a TXA2 receptor antagonist (vapiprost) and a TXA2 synthetase inhibitor (Y-20811) on a microcirculation disorder in the rat inner ear that was induced by a photochemical reaction between an intravenous injection of rose bengal (RB) and green light. A gradual decrease of the cochlear action potential (CAP) to an 8 kHz sound stimulus was measured with an electrocochleogram and occurred after the RB injection. The CAP then disappeared 5 min after the injection of RB. Both vapiprost and Y-20811 significantly prolonged the time required to complete suppression of the CAP as compared with saline as control. These findings indicate that TXA2 may play an important role in microcirculation disorders in the rat inner ear.

か牛マイクロフォン電位（ＣＭ）遅発反応 その特性と分析法

Cochlear microphonics (CM) and delayed response following CM (DRCM) were investigated in 10 guinea pigs. The acoustic stimuli used were 1 kHz and 4 kHz tone pips. DRCM could be detected in all animals with a threshold less than 35 dB pe SPL in cochlear action potential (AP), but decreased or became undetectable at AP thresholds over 40 dB pe SPL. The input-output curves of DRCM revealed typical nonlinear properties and showed the saturation phenomenon at fairly low sound intensity around 60 dB pe SPL, compared to the sound level at which CM is saturated. Thus, CM and DRCM could be separated by a modification of Probst's method, taking into account their different input-output functions. DRCM differed from CM by being independent of the frequency of acoustic stimulation, although it was dependent on the phase. DRCM seemed to contain relatively low frequency ranges, 0.5 to 2.0 kHz. Therefore, DRCM evoked by 4 kHz tone pips could be separated easily from CM by high-cut filtering. The waveform of DRCM, separated by a modification of Probst's method, was quite similar to that separated by high-cut filtering. Thus, DRCM is thought to be a different evoked potential from CM.

Frequency-specific enhancement of the cochlear compound action potential: Influence of the forward masker

Under restricted frequency and intensity conditions, forward masking can result in the amplitude of the CAP being increased above its unmasked value (Henry, 1991). The present study provides a quantitative analysis of this enhancement effect. In response to forward maskers having the same frequency as the probe stimulus, central frequency (CF) enhancement varies as a function of the level of the forward masker: the lowest masker level at which it can reliably be detected is often well below the visual detection threshold of the CAP generated by the unmasked probe stimulus; the highest masker level at which it can reliably be detected corresponds to approximately 10 dB above the probe stimulus CAP threshold. A second low frequency (LF) enhancement region also exists, encompassing a narrow range of more intense maskers. CF enhancement can double the amplitude of the CAP, whereas LF enhancement is less pronounced. The magnitude of CF enhancement varies as a function of the duration of the forward masker, with longer durations generally increasing the magnitude of the effect. This duration effect, however, interacts with the level of the stimulus. Decreasing the interval between the end of the forward masker and the beginning of the probe increases the magnitude of CF enhancement.

Measurements of perilymphatic oxygen tension in guinea pigs exposed to loud sound

Using different types of custom-made oxygen-sensitive microelectrodes, the perilymphatic oxygen partial pressure (PO2) was determined in anesthetized guinea pigs. Cochlear temperature, heart rate, and arterial blood pressure and acid-base status were monitored. The PO2 in the basal scala tympani perilymph (200 microns below the round window membrane) was found to be 53 +/- 17 mmHg (mean +/- SD) in 33 normal animals. In 11 guinea pigs exposed to loud sound for 15 min (10 kHz pure tone, 125 dB SPL) there was on average a continuous decline in the perilymphatic PO2, which was significant only 30 min post-exposure. A considerable variation in response was found in individual animals. Mean arterial blood pressures showed a slightly increasing time course, while heart rates did not change significantly during the whole period of the experiment. Arterial acid-base status and PO2 values remained within normal limits and did not change significantly. Cochlear microphonics and compound action potentials were substantially decreased after acoustic overstimulation. The results are discussed with due consideration of sources of error.

Effects of Circulatory Disturbance on the Cochlea

In order to determine the effects on the cochlea of circulatory disturbance in the basilar artery system, the cochlear action potential (AP) and the cochlear blood flow were measured in cats with the artery occluded. The occlusion was performed in the basilar, the anterior cerebellar and in the internal auditory arteries. During occlusion the decrease in the cochlear blood flow was greatest in the internal auditory artery and the least in the basilar artery. While the cochlear blood flow showed various levels of decrease depending on the occlusion site and the individual animal, the degree of AP alteration correlated with the decreased rate in the cochlear blood flow.

Latency and Amplitude Compound Action Potential Tuning Curves for Tonal Stimuli with Nontraditional Envelopes

To evaluate the influence of the acoustic context on the latency and amplitude tuning curves (TCs) of cochlear nerve compound action potentials (CAPs), tonal stimuli were generated with a variety of amplitude modulation envelopes. CAPs were produced by intensity increases (onsets) and decreases (offsets) from the low ambient sound level and by intensity changes from a preexisting tonal level. Onset CAPs from ambient levels generated V-shaped TCs. However, when simultaneous masking was used with onset CAPs which were produced by a 5- to 12-dB increase from preexisting levels of approximately 65 dB SPL, TCs were W-shaped and similar in appearance to those produced by simultaneous masking of offset CAPs. The forward masking of this same CAP resulted in a very sharp V-shaped TC. These data suggest that the preadaptation to 10 ms of a moderate level of a tonal stimulus can increase the tuning of ensembles of cochlear neurons to subsequent transient amplitude changes.

Influence of acoustic deprivation on recovery of hair cells after acoustic trauma

The purpose of this study was to investigate how the recovery of the cochlea, after acoustic trauma, might be influenced by acoustic stimulation or deprivation. In anaesthetized adult chinchillas, both ears were simultaneously exposed to a traumatizing acoustic stimulus (2 kHz tone, at 117 dB SPL for 15 min). Probe microphones positioned in both bullae were used to ensure identical exposure to the two ears; this was important because the experiment relies on within-animal controls. Cochlear action potential thresholds across frequency (CAP audiograms) were used to verify the similarity of threshold shifts to the two ears. Immediately following, a unilateral ossiculectomy was performed which resulted in one cochlea being acoustically deprived during the recovery period, whilst the other was not. In groups of animals with recovery periods of 1, 3, 6 and 12 weeks, both the acoustically deprived and the normally stimulated cochleas were examined with scanning electron microscopy. To quantify hair cell damage, we used a damage scale based on stereociliar integrity; for each cochlea, a standard region 5.5–8.5 mm from the apex was studied in detail. We found that after acoustic trauma, hair cell damage to the cochlea which is deprived of sound during the recovery period, is significantly greater compared with that in the normally stimulated, contra-lateral cochlea. Our results suggest that mechanical activation of the inner ear acts to inhibit long-term degenerative processes, or influence repair of partially damaged hair cells.

音響刺激後のか牛有毛細胞の回復 入力遮断の影響

This study was designed to investigate the effects of acoustic deprivation and stimulation following acoustic trauma.Symmetrical bilateral cochlear lesions were produced in 33 chinchillas by exposure to a high intensity pure tone (117dBSPL, 2kHz) for 15 minutes. Cochlear thresholds were derived from the cochlear action potentials (CAP) taken prior to and one day after exposure. Then the incudo-malleolar complex of one side was removed so that one cochlea was normally stimulated during the recovery period, while the other was deprived of sound. After a period of one to twelve weeks the OAP's on the non-deprived (nonoperated) side were measured. Hair cell damage in the acoustically deprived cochlea was assessed with scanning electron microscopy. In order to quantify the degree of damage to the sensory epithelium, a hair cell damage scale was implemented based on stereociliary integrity.The control group consisted of six chinchillas with unilateral ossiculectomy but no sound exposure, and four which received sound exposure only. The cochleas of these animals also were analyzed by scanning electron microscopy.The most significant result of this study was that the cochleas with acoustic deprivation during the recovery period sustained a higher degree of damage than the acoustically stimulated cochleas.Another result was that symmetrical cochlear lesions could be produced by strict monitoring of sound pressure balance in both middle ear cavities. Finally, careful ossiculectomy did not affect cochlear morphology.

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.

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.

Characterization of an EPSP-like potential recorded remotely from the round window.

The whole-nerve cochlear action potential (CAP), to tone burst stimulation, was recorded before and after application of tetrodotoxin (TTX) to the intact round window (RW) membrane. TTX abolished the CAP leaving a residual negative potential without altering the summating potential (SP) or the cochlear microphonic (CM). The residual potential retained its polarity when recorded from scala vestibuli. The peak latency, amplitude, and tuning properties of the residual potential showed features similar to the CAP. Application of kainic acid to the RW membrane eliminated the residual potential, leaving the SP and CM unaltered. It is hypothesized that the sources of the residual potential are the excitatory post-synaptic potentials from the peripheral processes of afferent dendrites under the inner hair cells.

Action potential tuning curves recorded with a derived response technique

A number of laboratories use tonal masking methods in conjunction with the cochlear action potential (AP) to generate AP tuning curves. In these studies, the amplitude of AP elicited by a probe stimulus is monitored as the level of masker is varied. An amplitude reduction (AR) by a specified amount (25%–100%) is used to indicate masking of the response. An alternative method was investigated in which interaction of the probe and masker is monitored by digital subtraction of the unmasked and masked responses, generating a tone‐derived (TD) response. An amplitude criterion of 10‐μV TD response is used to indicate masker/probe interaction. Tuning curves were recorded from the round window of anesthetized guinea pigs using AR and TD methods. With near threshold probe stimuli, similar tuning curves were obtained. With higher levels however, markedly different results were observed. AR tuning curves became elevated and sharper while TD curves became lower and broader. The TD method appears to better represent the frequency spread of responses with increasing stimulus level as demonstrated at the single unit level. In addition, TD tuning curves were able to detect second harmonic distortions of the probe stimulus, while AR tuning curves did not. [Work supported by Program project grant P01 NS24372 and Training Grant NS 07278.]

Electrically Stimulated Increases in Cochlear Blood Flow: II. Evidence of Neural Mediation

In a companion paper, we reported that electrical stimulation increased cochlear blood flow (CBF). This response was found to be an increasing function of current intensity and was frequency-selective, with the best response at approximately 500 Hz continuous sinusoidal current. The present investigation seeks to discover the mechanism of this effect. Direct measurement of cochlear temperature during electrical stimulation revealed no evidence of local heating. Autonomic neuronal activation is not likely, as neither atropine, hexamethonium, nor propranolol abolished the evoked CBF response. Strial activity could be suppressed by the use of furosemide, but the evoked CBF response persisted. Inactivation of auditory afferent neurons with kainic acid also did not change the evoked CBF response. Dimethyl sulfoxide, a potent oxygen-free radical scavenger, did suppress the evoked CBF response to a small but significant degree. This suggests that oxygen-free radicals may be produced within the cochlea during electrical stimulation. Finally, the evoked CBF response was completely suppressed by procaine and tetrodotoxin, with recovery of evoked CBF response accompanying recovery of cochlear action potentials. These data indicate that stimulation of neural fibers, distinct from autonomic and auditory afferent neurons, may modulate CBF.

Cochlear hypoxia and the compound action potentials.

A relatively restricted area, including the ear, was perfused in guinea pigs with hypoxic blood having a pO2 of 10, 20, and 30 mm Hg, respectively. The changes induced to the cochlear action potentials were analyzed and the results compared with those obtained in a previous study in which the guinea pigs were rendered hypoxemic by ventilating them with air entrapped in a closed circuit from which the CO2 was continuously absorbed. The changes induced to the cochlear action potentials by both methods were very similar. However, while using the territorial model for inducing hypoxia, 75% of the animals showed a threshold shift at a blood pO2 of 20 mm Hg and with the general model all the animals showed a threshold shift at 25 mm Hg blood pO2. In other words, if the hypoxic condition affected the whole body, other factors such as a slight, but continuous tendency to acidosis with significant increase in blood lactic acid concentration could join the oxygen deficit in affecting cochlear function.

Evolution of recruitment at different frequencies during the development of endolymphatic hydrops in the guinea pig.

The study of human temporal bones has identified endolymphatic hydrops as a common feature of several diseases. In particular it is systematically found in those bones removed from patients with premortem Menière's disease. Menière's disease is known to induce sensorineural pathology with recruitment, which changes with the evolution of the hearing loss, and is suspected to induce a cochlear conductive loss by a possible increase in static pressure of endolymph. Amplitude/intensity functions of sensorineural responses can reflect recruitment and/or conduction loss. Experimentally induced hydrops in animals provokes cochlear physiological alterations, some of which closely resemble certain features of Menière's disease. In the present study using a guinea-pig animal model, we have examined amplitude/intensity functions at the round window for cochlear microphonics (RWCM), summating potentials (RWSP) and action potentials (CAP) at different stages of hearing loss in experimentally induced hydrops. During the period of fluctuating thresholds there was reduction of maximal RWCM amplitude, no change in RWSP and recruitment on the CAP. At a later stage when the audiogram was flat and fluctuations were no longer seen, RWCM remained unchanged. At this time RWSP could show recruitment while CAP amplitudes at all intensities were reduced, indicating either a cochlear conductive loss and/or a general depression of neural activity.