Compound Action Potential and Cochlear Microphonic Extracted from Electrocochleographic Responses to Condensation or Rarefaction Clicks

In electrocochleography (ECochG) compound action potential (CAP) and summation potential (SP) are usually separated from the cochlear microphonic (CM) by the CM cancellation technique consisting in averaging the responses evoked by rarefaction and condensation clicks. With the aim of analysing the ECochG responses evoked by monophasic clicks, we developed a numerical method based on the theory of optimal filtering, which makes no assumptions about the unknown potentials. The application of the filtering technique to the ECochG recordings obtained from 6 normally hearing children and 10 children with cochlear hearing loss allowed us to perform CAP extraction in cases where CM was not cancelled by the conventional method. Differences in SP amplitude and polarity were found between rarefaction and condensation click-evoked responses in cochlear hearing losses.     

Compound action potential and cochlear microphonic extracted from electrocochleographic responses to condensation or rarefaction clicks

In electrocochleography (ECochG) compound action potential (CAP) and summation potential (SP) are usually separated from the cochlear microphonic (CM) by the CM cancellation technique consisting in averaging the responses evoked by rarefaction and condensation clicks. With the aim of analysing the ECochG responses evoked by monophasic clicks, we developed a numerical method based on the theory of optimal filtering, which makes no assumptions about the unknown potentials. The application of the filtering technique to the ECochG recordings obtained from 6 normally hearing children and 10 children with cochlear hearing loss allowed us to perform CAP extraction in cases where CM was not cancelled by the conventional method. Differences in SP amplitude and polarity were found between rarefaction and condensation click-evoked responses in cochlear hearing losses.     

Hearing impairment in patients with acoustic neuroma—analysis by electrocochleography

Objective: In patients with acoustic neuroma, the site and severity of hearing impairment are important in discussing surgical approaches. Since the effectiveness of conventional auditory psychological testing is limited, we studied objectively hearing impairment of the cochlea and the cochlear nerve due to the tumor. Methods: Electrocochleography (ECochG) was carried out in 21 patients with acoustic neuroma. Cochlear microphonic potential (CM) and action potential (AP) in ECochG evoked with clicks and short tone bursts were recorded through a transtympanic needle electrode technique. Cochlear function was studied using the detection thresholds of CM, and cochlear nerve involvement was analyzed by differences between AP and CM detection thresholds. Results: The 1 kHz CM detection threshold was elevated in 17 (81.0%) of 21 patients indicating cochlear impairment. Of seven patients with normal hearing or mild sensorineural hearing loss in pure tone audiometry, three had a slightly elevated CM detection threshold. Of five patients with pronounced pure tone levels, four showed a CM response and were thought to have mild cochlear dysfunction. Cochlear nerve impairment was confirmed in three of four patients with well-developed CM based on elevated AP detection thresholds. Three patients had CM response but no AP response, suggesting severe cochlear nerve impairment. Conclusion: Disorders of the cochlea and the cochlear nerve can be evaluated with ECochG AP and CM measurement. The findings of ECochG are thought to be important information to judge hearing prognosis, thereby enhancing its clinical utility.     

Abnormal positive potentials in round window electrocochleography

OBJECTIVE: To describe an atypical waveform, termed an abnormal positive potential (APP), on round window electrocochleograms (RW ECochG) of children and to relate its occurrence to clinical history. STUDY DESIGN: APPs were identified prospectively, and a retrospective analysis was made of these patients' clinical histories, audiograms, and auditory outcomes (hearing aid, cochlear implant, or nonauditory communication) SETTING: Tertiary referral teaching hospital, day surgery and clinics. PATIENTS: All 431 children <110 months of age suspected of a severe to profound hearing loss who underwent RW ECochG from January 1993 to August 1997. INTERVENTION: Diagnostic RW ECochG for auditory threshold estimation. MAIN OUTCOME MEASURE: The presence on the RW ECochG of the APP: an early positive potential in the absence of a compound action potential (CAP). RESULTS: An APP was observed in 34 children. The APP was most marked in response to clicks and 8-kHz tones. The APP click threshold averaged 70 dB hearing loss. The brainstem evoked potential of these children showed an absence of waves, or a broad positive wave with no subsequent waves. Twenty-nine of 30 behavioral audiograms obtained were indicative of severe to profound hearing loss. Auditory outcomes were available from 26 children; 45% of them derived no help from a hearing aid, and 8 children received a cochlear implant. Clinical factors frequently associated with APP were prematurity in combination with kemicterus or hypoxia. CONCLUSIONS: APP thresholds were lower than neural thresholds or behavioral thresholds. Children with APP need close follow-up, because half of those studied needed nonauditory strategies to develop effective communication.     

Electrocochleography in auditory neuropathy

Auditory neuropathy (AN) is a disorder characterized by the absence or the severe impairment of the auditory brainstem responses (ABRs) together with the preservation of otoacoustic emissions and/or cochlear microphonic (CM). We recorded transtympanic electrocochleography (ECohG) evoked by 0.1 ms clicks in one young adult and in four children having distortion product otoacoustic emissions and absent ABRs. In all but one patient CM and summating potential (SP) were present with normal threshold, and their amplitudes appeared comparable to or higher than the values obtained from subjects with normal hearing. The compound action potential (CAP) was absent in two patients while in one subject CM and SP were followed by a highly desynchronized neural activity. A broad CAP was found in two children and the threshold appeared clearly elevated in one of them, while it showed only a mild elevation in the other. No correlation was found between CAP and behavioral thresholds. These results suggest that ECohG can be useful in AN diagnoses since it is the only reliable tool in evaluating the auditory peripheral function in the presence of a desynchronized ABR.     

Auditory neuropathy in systemic sclerosis: a speech perception and evoked potential study before and after cochlear implantation

We report the results of speech perception and electrophysiological evaluation of the auditory periphery performed before and after cochlear implantation in a 18-year-old girl with systemic sclerosis (SS) who presented the clinical picture of auditory neuropathy. Transtympanic electrocochleography (ECochG) in response to 0.1 ms clicks was recorded 1 month before cochlear implantation on both sides while the electrically evoked neural response was obtained intraoperatively in the right ear through cochlear implant stimulation. The ECochG recordings revealed the presence of the cochlear microphonic with normal amplitude and threshold on both sides. A compound action potential was only detected in the left ear at high stimulation intensity, while the electrically evoked neural response was clearly identifiable at all the recording sites during neural response telemetry. Standardized speech perception tests were performed 1 month before cochlear implantation and several times after cochlear implant connection. Speech perception scores were close to chance before cochlear implantation while they showed a remarkable improvement thereafter. The results of this study show that subjects affected by SS could present the clinical picture of auditory neuropathy which is possibly underlain by lesions involving the distal portion of auditory nerve fibers and/or synapses with inner hair cells. The restoration of synchronous neural discharge could be achieved by electrical stimulation through cochlear implant.     

Electrocochleography in cochlear implantation: Development,applications, and future directions

Electrocochleography (ECochG) is an electrophysiological technique that records electrical potentials generated by different components of the inner ear and peripheral cochlear nerve in response to acoustic stimulation. ECochG responses can be analyzed into (1) cochlear microphonics (CM), (2) auditory nerve neurophonics, (3) summating potential, and (4) compound action potential. Over the past few decades, there have been ongoing refinements in technique and updates in the understanding of recorded potentials. Historically, ECochG found its main application in the diagnostic evaluation of Meniere’s disease (MD). However, in the last decade, the focus has shifted towards cochlear implantation (CI). In patients with residual hearing after CI, combined electric and acoustic stimulation has resulted in improved hearing and speech outcomes. Despite efforts to mitigate trauma during electrode insertion, hearing preservation rates vary after surgery. During implantation, real-time ECochG offers an opportunity to measure frequency specific CMs elicited from a localized region in the cochlea as the surgeon inserts the electrode array. In extracochlear ECochG recordings, the recording electrode can be placed on the promontory, the stapes, or the tympanic membrane. Intracochlear ECochG can be performed by inserting a recording electrode into the cochlea or by using one of the CI electrodes as the recording electrode. The loss of intraoperative ECochG signal may indicate cochlear trauma from electrode insertion, but the association between intraoperative ECochG changes and cochlear trauma remains controversial. The ability to monitor cochlear trauma during CI electrode placement holds promise to improve hearing preservation outcomes, modify surgical techniques, and change electrode design. The goal of this review is to provide a comprehensive overview of the electrophysiology and history of ECochG, discuss its recent applications in CI, and explore the ongoing research in this expanding field.     

Electrophysiologic examinations in low frequency hearing impairment: clinical and prognostic aspects

INTRODUCTION: Low-frequency hearing impairment (LFHI) is mainly associated to endolymphatic hydrops and shows a high variety of possible outcomes. Electrophysiologic examinations are widely recommended in diagnostics of LFHI, wheras up to now no data exist about the prognostic value of these examinations in a conservative therapeutic regimen. METHODS: In a quality assessment, we retrospectively evaluated the records of 90 patients, and performed an audiometric follow-up for analysis of long-time hearing data. All patients had undergone diagnostic electrocochleographic examination (ECochG) and then had been treated with rheologic infusions, followed by dehydrating infusions in patients lacking complete remission. The results of both therapeutic strategies and of long-time results were correlated to electrophysiologic findings. RESULTS: The prognosis of LFHI is significantly reflected by pretherapeutic electrocochleographic data. All significant parameters were associated to compound action potential (CAP) whereas parameters associated to cochlear microphonics (CM) did not include any utilizable prognostic value. In patients with a good outcome, the latency of CAP complex was significantly shorter, and the width of CAP complex significantly smaller than in patients with poor hearing outcome after rheologic and after dehydrating therapy and in long time assessment. The relation of summating potential (SP) und CAP was significantly smaller when the outcome was sufficient or good for either therapy and in long time analysis. Steep CAP-input-output-curves were associated to insufficient outcome after rheologic therapy and in long time assessment, but not for dehydrating therapy. CONCLUSIONS: The results indicate that ECochG is of significant prognostic value concerning hearing outcome after conservative therapy in patients suffering from LFHI. It can help the physician to counsel the patient and perform an effective management of the disease. We conclude that ECochG should be performed before the onset of therapy, including collection of SP and CAP data whereas CM parameters may be omitted.     

Reliability of cochlear microphonics in clinical electrocochleography

A study was made on the reliability of cochlear microphonics (CM) recorded in clinical electrocochleography (ECochG) by the transtympanic electrode technique. In normal-hearing subjects, the CM shift increased as the frequency was lowered at the same sound pressure, and as the sound pressure was lowered at the same frequency. The CM shift for the frequencies from 8 to 0.5 kHz was greater as the sound pressure was lowered. The above results suggest that clinical ECochG CM responses may well reflect the potential of the cochlea.     

Nimodipine, an L-channel Ca2+ antagonist, reverses the negative summating potential recorded from the guinea pig cochlea

Nimodipine, an L-type Ca2+ channel antagonist, was tested using sound-evoked cochlear potentials in guinea pigs to investigate whether these channels are involved in cochlear function. Perilymph spaces of guinea pig cochleae were perfused with artificial perilymph solutions containing 0.1-10 microM nimodipine at a rate of 2.5 microliters/min for 10 min. The cochlear potentials evoked by 10 kHz tone bursts of varying intensities were recorded from the basal turn of the scala vestibuli. Cochlear perfusion of nimodipine resulted in reversible, dose-related suppression of the compound action potential of the auditory nerve (CAP; N1-P1), a prolongation of N1 latency at suprathreshold levels, an elevated CAP threshold, a decrease in N1 latency at a constant amplitude measured at CAP threshold, a reduction in cochlear microphonics (CM), and a reduction of the negative summating potential (SP) to a point where it became positive (i.e., a reversal of SP). The endocochlear potential (EP) was not affected. These results support the hypothesis that L-type Ca2+ channels are directly involved in the operation of the organ of Corti. We speculate that L-type Ca2+ channels are integrally involved in generation of a negative summating potential and the dc motion of the cochlear partition described by others.     

Brainstem and cochlea potentials evoked by rarefaction and condensation single-slope stimuli. A preliminary report

Influences of stimulus polarity on Jewett wave V are rather small when using clicks which produce two or more polarity changes within a short time interval. In order to separate pressure changes towards rarefaction (R) and towards condensation (C) we applied steep single-slope stimuli returning very slowly to baseline. Brainstem responses recorded from 8 human subjects differed markedly for R and C onset. Amplitudes were much higher for R than for C onset. The main C response was double-peaked with the first peak appearing about 0.5 ms earlier and the second, higher one, 1 ms later than the predominant R wave. The transition from single-slope to click stimulation was investigated by combining R and C slopes. For large time intervals, independent responses to either slope were observed. Down to an on/off interval of 1 ms, the on-response predominated. For still shorter intervals an equalization of R and C responses and a graduation towards click responses was found. Using the same stimuli, cochlear microphonics (CM) and compound action potentials (CAP) were recorded from 7 guinea pigs. The CM did not replicate the slow off-motion of the single-slope stimulus, but returned back to baseline after 0.6 ms. The C compared with R latency of the CAP (peak N1) was also delayed by 0.6 ms. This delay, and that of human peak V, may be explained by CAP initiation only by one direction of basilar membrane motion.     

The effect of BAPTA and 4AP in scala media on transduction and cochlear gain

We have injected by iontophoresis 4-amino-pyridine, a K+ channel blocker and BAPTA, (a Ca++ chelator), into scala media of the first three turns of the guinea pig cochlea. We measured the reduction in outer hair cell (OHC) receptor current, as indicated by cochlear microphonic measured in scala media evoked by a 207 Hz tone, and compared this with the elevation of the cochlear action potential (CAP) threshold. We found that in the basal turn, for frequencies between 12 and 21 kHz, CAP threshold was elevated by about 30 dB, while in the second turn, at the 3 kHz place, the maximum elevation was 15 dB. In the third turn, iontophoresis of 4AP and BAPTA reduced CM by similar amounts to that in the basal and second turn, but caused negligible elevation of CAP threshold. We conclude that the gain of the cochlear amplifier is maximal for basal turn frequencies, is halved at 3 kHz, and is reduced to close to one for frequencies below 1 kHz (no active gain). The effect of 4AP and BAPTA on neural threshold and the receptor current represented by CM may be explained by their action on OHC transduction without the involvement of IHCs.     

人工耳蜗植入术中圆窗耳蜗电图评价耳蜗残余听功能

目的应用术中圆窗耳蜗电图评估极重度感音神经性聋患者耳蜗残余听功能。方法20例患者全麻下人工耳蜗植入手术过程中,行术中圆窗耳蜗电图测试,测出的复合动作电位（CAP）阈值与术前纯音测听或其他听力测试之阈值进行比较。结果20例患者术中圆窗耳蜗电图测试测出的复合动作电位（CAP）阈值与术前1、2、4kHz听力测试阈值分别有较好的相关系数（0．20429,0．04076,0．38163）。结论术中圆窗耳蜗电图可以较准确客观地评估极重度感音神经性聋患者耳蜗残余听功能,且是人工耳蜗植入术前听力学评估方法的有意义的补充。     

An interaction between PPADS, an ATP antagonist, and a moderately intense sound in the cochlea

In the organ of Corti ionotropic receptors for ATP (ATPRs) on cells that are bathed by perilymph have been suggested to modulate cochlear mechanics. The purpose of the present study was to test the hypothesis that endogenous extracellular ATP acting through ATPRs is involved in modulating cochlear mechanics during moderately intense sound exposure. Guinea pigs were exposed to either: (1) a perilymphatic administration of pyridoxal-phosphate-6-azophenyl-2', 4'-disulfonic acid (PPADS, 1 mM), an ATP antagonist; (2) a moderately intense sound (6.7 kHz tone, 95 dB SPL, 15 min); or (3) a combination of both the PPADS and the sound. The effects on cochlear potentials (cochlear microphonic, CM; negative summating potential, SP; compound action potential of the auditory nerve, CAP; and N(1) latency) evoked by a 10 kHz tone pip were monitored. PPADS alone reduced the CAP and the SP and increased N(1) latency. The intense sound alone reduced the CAP and SP. The combination of PPADS with the intense tone induced reversible effects on cochlear potentials that were greater than induced by either treatment alone. The effect on N(1) latency and low intensity CM was a potentiation since the effect was greater than a simple addition of the effect of either treatment alone. The effects of the combination treatment on CAP, SP and high intensity CM were not different from additive. Results are consistent with the hypothesis that ATPRs in the organ of Corti are involved in modulating cochlear mechanics during moderately intense sound exposure.     

Corresponding effects of hypoxia on the cochlear microphonic and the compound action potential

Mild hypoxia has an unexpected influence on the compound action potential (CAP) compared to its effect on the cochlear microphonic (CM). While the CM decreases in amplitude near threshold, the low-level CAP increases in amplitude by as much as 400% and decreases in latency and width. The magnitude of latency decrease is dependent on the center frequency of $\text{1}\text{3}$ octave band-filtered clicks used as stimuli. Below 13500 Hz the latency is increasingly shortened at a rate of 0.073 ms/octave. At high intensities moderate hypoxia has no effect on either the CM or the CAP. However, with more severe hypoxia the high-level CM also begins to deteriorate. Correspondingly both the high- and low-intensity CAP decrease in magnitude and increase in latency relative to their control values. Assuming that the low-level CM is generated by outer hair cells, these results suggest that one relationship between outer hair cell function and auditory nerve function near threshold is that of inhibition. The fact that N₁ latency is shortened suggests that this inhibition occurs in the basalward direction.     

顺铂中毒后豚鼠耳蜗电位变化的特征及形态学实验观察

目的 观察顺铂对耳蜗微音电位（ＣＭ）、总和电位（ＳＰ）及复合动作电位（ＣＡＰ）的影响及毛细胞形态学改变。方法 用人工外淋巴液和顺铂灌流豚鼠耳蜗，分别记录耳蜗第三回中阶的ＣＭ、－ＳＰ及ＣＡＰ，琥珀酸脱氢酶染色观察毛细胞的数量变化，透射电镜观察外毛细胞结构。结果 顺铂灌流１ｈ：≤６０ｄＢ ＳＰＬ声强级刺激时ＣＭ、－ＳＰ和ＣＡＰ幅度均较灌流顺铂前略下降，≥７０ｄＢ ＳＰＬ声强级刺激时幅度比灌流顺铂前明显     

Non-linear aspects of outer hair cell transduction and the temporary threshold shifts after acoustic trauma

The 200-Hz cochlear microphonic potential (CM) and the compound action potential (CAP) of the auditory nerve evoked by tone-bursts were recorded in the basal turn of the cochlea of anaesthetised guinea pigs, before and after exposure to traumatic high-frequency tones that produce a temporary threshold shift (TTS) in this cochlear region. The drop in CM and the TTS were highly correlated, suggesting that it is the disruption of the outer hair cells generating the CM that causes the TTS. The previously measured rise in endocochlear potential and drop in organ of Corti K+ levels suggest that the TTS is due to a temporary closure of outer hair cell mechanoelectrical transduction (MET) channels, which produces a drop in the mechanical sensitivity of the organ of Corti, due to disruption of the active process provided by outer hair cells. The time course of the onset and recovery of TTS is consistent with a kinetic folding and refolding of MET channels over a time course of hours and days. Mathematical modelling of this putative channel folding suggests that TTS recovery may be accelerated by the presentation of additional sounds during the recovery period. We present electrophysiological data (CM and CAP measurements) showing that this accelerated recovery occurs. Using two-tone complexes (phase-locked 5- and 10-kHz traumatic tones, and 10-kHz traumatic tones with 25-Hz bias tones), we also show that the mechanisms producing TTS are non-linear and asymmetric, and that the greatest 'trauma' occurs when the hair bundles of outer hair cells are deflected away from the basal body of these cells (i.e. in the direction normally causing hyperpolarisation of the cell membrane potential).     

effects of glutamate on distortion-product otoacoustic emissions and auditory brainstem responses in guinea pigs

Objective To investigate changes in evoked potentials and structure of the guinea pig cochleae during whole cochlear perfusion with glutamate. Methods CM, CAP, DPOAE, and ABR were recorded as indicators of cochlear functions during whole cochlear perfusion. The morphology of the cochlea was studied via transmission electron microscopy. Results There were no significant changes in DPOAE amplitude before and after glutamate perfusion. CM I/O function remained nonlinear during perfusion. ABR latencies were delayed following glutamate perfusion. The average CAP threshold was elevated 35 dB SPL following glutamate perfusion.. The OHCs appeared normal, but the IHCs and afferent dendrites showed cytoplasmic blebs after glutamate perfusion. Conclusions While being a primary amino acid neurotransmitter at the synapses between hair cells and spiral ganglion neurons, excessive glutamate is neurotoxic and can destroy IHCs and spiral ganglion neurons. The technique used in this study can also be used to build an animal model of auditory neuropathy.     

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.