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.     

Electrocochleography potentials evoked by condensation and rarefaction clicks independently derived by a new numerical filtering approach

The cochlear microphonic potential (CM) and the compound action potential (CAP) cannot be measured separately but only in combination. In the literature their individual estimates are conventionally recovered by the so-called CM cancellation technique. This method averages the potential obtained in response to rarefaction and condensation clicks under the assumption that changing the polarity of the clicks only affects the CM sign and does not alter the CAP in any way. However, both theory and evidence suggest that these hypotheses can be critical. In addition, recent contributions in the electrocochleography (ECochG) literature suggested that assessing the influence of stimulus polarity on the evoked CAP may constitute an indicator of clinical usefulness which the CM cancellation method cannot supply. In this work we propose a new algorithm to estimate the cochlear potentials evoked from positive clicks, CAP+ and CM+, and those evoked from negative clicks, CAP- and CM-, by processing the same kind and amount of data employed in the CM cancellation method. The application to real data taken from 3 subjects exhibiting quantitatively and qualitatively different ECochG responses at various levels of stimulation intensity is presented. In addition, simulated problems where the true CAP and CM are known are studied to permit a fair assessment of the proposed technique. Results suggest that the new algorithm is potentially able to point out small differences between CAP+ and CAP-. This encourages its further employment on a larger scale.     

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.     

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.     

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.     

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.     

Cochlear summating potential to broadband clicks detected from the human external auditory meatus. A study of subjects with normal hearing for age

The cochlear summating potential (SP) preceding the auditory nerve compound action potential (AP) was elicited by broadband alternating condensation and rarefaction clicks and recorded by noninvasive electrodes from the external auditory meatus (EAM) of 60 volunteers of both sexes, 12 to 67 years old, who had normal hearing for age. Quantitative data were obtained on: the number of ears displaying measurable SPs; the SP detection level; the SP onset, peak and rise times; the duration of the SP-AP complex; the SP amplitude; and the SP/AP amplitude ratio. Previously unknown relationships were unveiled between the amplitude, but not the temporal, measures of the SP and laterality, sex, age, and audiometrically determined hearing thresholds to 4 to 8 kHz tones. The highest correlations were obtained with these last thresholds, which suggested that receptors in the basal turn of the cochlea played a dominant role in the generation of the EAM-detected SP. To improve on existing techniques for determining abnormal SP elevation, a multiple regression method was devised that utilized sex, age, 4 to 8 kHz hearing thresholds, and AP voltage to establish upper normal limits of SP amplitude for individual subjects and ears.     

疏波和密波短声诱发的动作电位潜伏期差对梅尼埃病的诊 …

OBJECTIVE: To study the value of condensation and rarefaction clicks evoked action potential (AP) latency difference (LD) in diagnosis of Meniere's disease. METHODS: AP was recorded with ECochG in controls (50 ears) and patients with Meniere's disease(90 ears) and sensorineural hearing loss(SNHL) of other origins(60 ears). LD was calculated and analyzed. RESULTS: LD in patients with Meniere's disease was (0.30 +/- 0.15) ms, which was significantly larger than that of controls(0.18 +/- 0.07) ms and of patients with SNHL of other origins(0.20 +/- 0.10) ms (P < 0.01). In the group of Meniere's disease, LD in patients with the mild and moderate hearing impairment was larger than those with severe hearing loss(P < 0.01) and LD in patients with low tone or high tone auditory sensation curve was larger than those with flat auditory sensation curve(P < 0.01). Positive rate was 4/60(6.7%) in other SNHL patients and 58/90(64.0%) in Meniere's disease group respectively. CONCLUSION: The increase in condensation and rarefaction click evoked AP latency difference can be an objective parameter in diagnosis of Meniere's disease.     

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.     

Effect of click spectrum and polarity on round window N1N2 response in the rat

The effect of the duration of click stimuli on the compound action potential recorded from the round window in the rat and the effect of low-pass filtering of short click sounds were studied. Thus the intensity functions of the round window N1 potential have a two-segment course and there is a difference in the response to rarefaction and condensation clicks, depending upon the content of low-frequency components in the click stimulus. The intensity function of the rat's response to broadband clicks does not show the same two-segment course as has been reported in experiments in other animals, and there is little difference between the response to condensation clicks and that to rarefaction clicks in this animal. However, when the duration of the click is increased or when broadband clicks are subjected to low-pass filtering, the intensity functions in response to condensation clicks do show a change in course, while the response to rarefaction clicks remains essentially unchanged. A similar change in the response to a broadband click can be induced by adding a low-pass-filtered click to the broadband click. The response to such a combination is not only a linear summation of the neural response to the individual components of the stimuli and the cochlear microphonics, but the low-frequency components that are added also affect the response to the broadband click, mainly by reducing the amplitude of the response.     

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.     

Compound action potentials recorded from the intracranial portion of the auditory nerve in man: effects of stimulus intensity and polarity

Compound action potentials (CAP) were recorded from the intracranial portion of the eighth nerve in patients with normal hearing who were undergoing neurosurgical operations for cranial nerve disorders (trigeminal neuralgia and hemifacial spasm). Brain-stem auditory-evoked potentials were recorded intraoperatively to ensure that no noticeable changes occurred in conduction in the auditory nerve as a result of surgical dissections. The CAP recorded from the middle portion of the exposed intracranial portion of the eighth nerve in response to clicks of high intensity (100-110 dB peak equivalent SPL, or pe SPL) had a triphasic shape, as is commonly seen in monopolar recordings from long nerves. A second negative peak (N2) could be identified in some patients. There was little difference in the waveform of the CAP in response to condensation and rarefaction clicks, and in some patients the waveform of the CAP remained the same over a range of stimulus intensities (from 105 to 75 dB pe SPL), whereas in others the negative peak of the CAP became much broader in response to stimuli with intensities of less than 85 dB. In some patients the N2 peak became dominant as the stimulus intensity was decreased. At low stimulus intensities, the response consisted of a single, broad negativity. The latency-intensity curves for the N1 peak had different slopes in different patients. In those individuals in whom there was a noticeable difference between the latency of the N1 peak in response to clicks of opposite polarity, the latency-intensity curves of the responses to rarefaction clicks were steeper than those of the responses to condensation clicks, and the latency of the N1 peak to condensation clicks became shorter than that to rarefaction clicks at intensities below 85-90 dB pe SPL. The latency-intensity curves for the N2 peak were usually less steep than those of the N1 peak, but in some patients the curves for these two peaks had similar slopes. The amplitude of the N1 peaks showed a steep increase in click intensities at 95 and 105 dB, and a much less steep course for intensities below 95 dB. The amplitudes of the N2 peak reached a plateau in the range 95-105 dB, and decreased more rapidly than the N1 peak below 95 dB.     

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.     

Audiological and electrocochleography findings in hearing-impaired children with connexin 26 mutations and otoacoustic emissions

We recorded cochlear potentials by transtympanic electrocochleography (ECochG) in three hearing-impaired children with GJB2 mutation who showed otoacoustic emissions. Pure tone thresholds, distortion product otoacoustic emissions (DPOAEs) and, auditory brainstem responses (ABRs) were also obtained. Subjects 1 (35delG/35delG) and 3 (M34T/wt) had profound hearing loss and showed the picture of auditory neuropathy (AN) as DPOAEs were detected with absent ABRs in both ears. The hearing impairment found in subject 2 (35delG/35delG) was profound in the right ear and moderate in the left ear. Both DPOAEs and ABRs with normal latencies and morphology were recorded only from the left ear. On the ECochG recording the cochlear microphonic was obtained from all children. No compound action potential (CAP) was detected in subject 1. A neural response was recorded only from the left ear in subject 2 with a threshold corresponding to the audiometric threshold while no CAP was detected on the right side. The ECochG obtained from subject 3 showed a low-amplitude broad negative deflection which was identifiable down to low stimulus levels. This response decreased in amplitude and duration when utilizing a high-rate stimulation paradigm. The amount of amplitude reduction was close to that calculated for normal ears, thus revealing the presence of an adapting neural component. These findings indicate that patients with GJB2 mutations and preserved outer hair cells function could present with the picture of AN. The hearing impairment is underlain by a selective inner hair cell loss or a lesion involving the synapses and/or the auditory nerve terminals. We suggest that neonatal hyperbilirubinemia may play a role in protecting outer hair cells against the damage induced by GJB2 mutations.     

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。     

The correlation between ECochG parameters and early auditory behavior after cochlear implantation in children

Objective: The individual outcome after cochlear implantation in children with auditory synaptopathy/neuropathy (AS/AN) is difficult to predict. A tool for preoperative assessment would be helpful for counseling parents. This study evaluates the outcome after CI in children with AS/AN and with sensorineural hearing loss (SNHL), and correlates it with the preoperative ECochG results in order to find specific parameters of prognostic value. Design: The improvement of auditory behavior after CI was retrospectively assessed using the LittlEARS questionnaire and quantified in a score (LS). This score was correlated with the CAP/SP ratio in the preoperative ECochG. The score was further correlated with the patient’s age six months following CI. Study sample: Nine children with AS/AN were compared to nine children with SNHL. Results: Both groups showed a significant improvement in LS following CI. There was a significant positive correlation between the CAP/SP ratio and the improvement in LS in all children. The correlation between age and LS was significantly negative in the SNHL group and positive in the AS/AN group. Conclusion: All children with AS/AN and SNHL benefit to a similar extent from CI. The preoperatively assessed CAP/SP ratio has a prognostic value for the development of auditory behavior following CI.     

Frequency-specific electrocochleography indicates that presynaptic and postsynaptic mechanisms of auditory neuropathy exist

OBJECTIVES: The physiological mechanisms underlying auditory neuropathy (AN) remain unclear and it is likely that the multiple disruptions are classified under the broadly defined term. Cochlear implantation is being more widely used in this population to bypass the suspected site-of-lesion although a number of cases have been identified within the Sydney Cochlear Implant Centre where this management strategy has been unsuccessful. It is likely that this relates to the different physiological mechanisms underlying AN. DESIGN: To investigate the site-of-lesion in AN, frequency-specific round window electrocochleography (ECochG) was used to assess local hair-cell, dendritic, and axonal currents generated within the cochlea in 14 subjects with AN and compared with responses from two normally hearing subjects. ECochG results were then compared with electrically evoked auditory brain stem response (EABR) measured after cochlear implantation. RESULTS: The results of this study demonstrate that two dominant patterns of ECochG waveforms (produced by a high-frequency alternating tone burst) can be identified in this population of AN subjects: (a) gross waveform showing a prolonged summating potential (SP) latency that, in most cases, is followed by a small compound action potential; and (b) gross waveform showing a normal latency SP waveform followed by a broad negative potential [assumed to reflect the dendritic potential (DP) identified in anaesthetized guinea-pigs]. This study demonstrates that in most subjects (n = 7) with a prolonged latency SP but no DP, normal morphology EABR waveforms were elicited for all electrode channels. On the other hand, all subjects (n = 7) who showed a normal latency SP followed by a broad negative DP, showed EABR waveforms that were absent or having poor wave V morphology. The authors' interpretation of this is that ECochG results may provide a classification of AN into pre- and postsynaptic lesions. CONCLUSIONS: We suggest that a presynaptic and postsynaptic type of AN exist that may have implications for the fitting of cochlear implants.     

Compound Action Potentials Recorded from the Intracranial Portion of the Auditory Nerve in Man: Effects of Stimulus Intensity and Polarity

Compound action potentials (CAP) were recorded from the intracranial portion of the eighth nerve in patients with normal hearing who were undergoing neurosurgical operations for cranial nerve disorders (trigeminal neuralgia and hemifacial spasm). Brainstem auditory-evoked potentials were recorded intraoperatively to ensure that no noticeable changes occurred in conduction in the auditory nerve as a result of surgical dissections. The CAP recorded from the middle portion of the exposed intracranial portion of the eighth nerve in response to clicks of high intensity (100-110 dB peak equivalent SPL, or pe SPL) had a triphasic shape, as is commonly seen in monopolar recordings from long nerves. A second negative peak (N²) could be identified in some patients. There was little difference in the waveform of the CAP in response to condensation and rarefaction clicks, and in some patients the waveform of the CAP remained the same over a range of stimulus intensities (from 105 to 75 dB pe SPL), whereas in others the negative peak of the CAP became much broader in response to stimuli with intensities of less than 85 dB. In some patients the N² peak became dominant as the stimulus intensity was decreased. At low stimulus intensities, the response consisted of a single, broad negativity. The latency-intensity curves for the N¹ peak had different slopes in different patients. In those individuals in whom there was a noticeable difference between the latency of the N¹ peak in response to clicks of opposite polarity, the latency-intensity curves of the responses to rarefaction clicks were steeper than those of the responses to condensation clicks, and the latency of the N¹ peak to condensation clicks became shorter than that to rarefaction clicks at intensities below 85–90 dB pe SPL. The latency-intensity curves for the N² peak were usually less steep than those of the N¹ peak, but in some patients the curves for these two peaks had similar slopes. The amplitude of the N¹ peaks showed a steep increase in click intensities at 95 and 105 dB, and a much less steep course for intensities below 95 dB. The amplitudes of the N² peak reached a plateau in the range 95–105 dB, and decreased more rapidly than the N¹ peak below 95 dB.     

自适应滤波提取耳蜗微音器电位初探

为解决表面电极引导耳蜗微音器电位的结果中存在刺激伪迹信号的状况，探讨了用自适应滤波处理抵消刺激伪迹信号提取的方法，结果发现：正常耳的ＣＭ较同侧表面电极引导的波形有一定的滞后时间，２ｋＨｚ以上的神经动作电位波形分化明显；３１耳极重度感音神经性聋和１１耳中度或中重度感音神经性聋耳各频率的ＣＭ消失，９耳极重度感音神经性聋和２９中度和中重度感音神经性聋各频率存在较好的ＣＭ波形。提示：不同程度的感音神经性聋     

Abnormal Cochlear Potentials from Deaf Patients with Mutations in the Otoferlin Gene

Otoferlin is involved in neurotransmitter release at the synapse between inner hair cells (IHCs) and auditory nerve fibres, and mutations in the OTOF gene result in severe to profound hearing loss. Abnormal sound-evoked cochlear potentials were recorded with transtympanic electrocochleography from four children with otoferlin (OTOF) mutations to evaluate physiological effects in humans of abnormal neurotransmitter release from IHCs. The subjects were profoundly deaf with absent auditory brainstem responses and preserved otoacoustic emissions consistent with auditory neuropathy. Two children were compound heterozygotes for mutations c.2732_2735dupAGCT and p.Ala964Glu; one subject was homozygous for mutation p.Phe1795Cys, and one was compound heterozygote for two novel mutations c.1609delG in exon 16 and c.1966delC in exon 18. Cochlear potentials evoked by clicks from 60 to 120 dB peak equivalent sound pressure level were compared to recordings obtained from 16 normally hearing children. Cochlear microphonic (CM) was recorded with normal amplitudes from all but one ear. After cancelling CM, cochlear potentials were of negative polarity with reduced amplitude and prolonged duration compared to controls. These cochlear potentials were recorded as low as 50–90 dB below behavioural thresholds in contrast to the close correlation in controls between cochlear potentials and behavioural threshold. Summating potential was identified in five out of eight ears with normal latency whilst auditory nerve compound action potentials were either absent or of low amplitude. Stimulation at high rates reduced amplitude and duration of the prolonged potentials, consistent with neural generation. This study suggests that mechano-electrical transduction and cochlear amplification are normal in patients with OTOF mutations. The low-amplitude prolonged negative potentials are consistent with decreased neurotransmitter release resulting in abnormal dendritic activation and impairment of auditory nerve firing.