Cochlear Potentials Research Articles

Establishment of a cochlear injury model using bone-conducted ultrasound irradiation in guinea pigs and investigation on peripheral coding and recognition of ultrasonic signals

The cochlea of guinea pigs was irradiated with different frequencies of bone-conducted ultrasound (BCU) at a specific dose to induce cochlear hair cell-specific injuries, in order to establish frequency-related cochlear hair cell-specific injury models. Cochlear near-field potentials were then evoked using BCU of different frequencies and intensities to explore the peripheral coding and recognition of BCU by the cochlea. The inner ears of guinea pigs were irradiated by 30 kHz at 100 db and 80 kHz at100 db BCU for 6h to create frequency-related, ultrasound-specific cochlear injury models. Then, 30 kHz and 80 kHz BCU of different intensities were used to evoke auditory brainstem response (ABR) thresholds, compound action potential (CAP) thresholds, and action potential (AP) intensity-amplitude input-output curves in the normal control group and the ultrasonic cochlear injury group. This allowed us to explore the coding and recognition of BCU frequencies and intensities by cochlear hair cells. Immunofluorescence assay of outer hair cell (OHC) Prestin and inner hair cell (IHC) Otofelin was performed to verify the injury models. Irradiation of guinea pig inner ears by 30 kHz and 80 kHz BCU at a specific dose induced hair cell injuries at different sites. Irradiation with low frequency BCU mainly induced OHC injury, whereas irradiation with high frequency BCU induced IHC injury; moreover, IHC injury was more serious than OHC injury. The 30 kHz-evoked ABR threshold was significantly higher in the 30 kHz ultrasonic cochlear injury group compared to the normal control group. The 30 kHz-evoked ABR threshold was significantly higher in the 30 kHz ultrasonic cochlear injury group compared to the 80 kHz ultrasonic cochlear injury group. The difference in the 80 kHz-evoked ABR thresholds were not significant between the 30 kHz and 80 kHz ultrasonic cochlear injury groups. The click- and 30 kHz-evoked AP intensity-amplitude curves for the 30 kHz ultrasonic cochlear injury group indicate that the AP amplitude evoked at the same intensity was higher in the 30 kHz-evoked group than the click-evoked group. The spatial positions of cochlear hair cells in guinea pigs had a coding function for the frequencies of low-frequency ultrasound. OHCs have an amplification effect on the coding of low-frequency ultrasonic intensities. The peripheral perception of high frequency BCU may not require the participation of cochlear hair cells.

Author response: Clinical Reasoning: A young woman with respiratory failure, hearing loss, and paraplegia.

We thank Drs. Bhatt and Adams for the thoughtful comment on our article.1 Hypoxia affects cochlear function in many ways,2–5 including a rapid decline in both endocochlear and other cochlear potentials (i.e., cochlear microphonic, distortion-product otoacoustic emission, and compound action potential),6,7 as well as inducing histologic and cellular changes.8 Moreover, hypoxia, in the form of apneic spells, is a significant clinical predictor of newborn sensorineural hearing loss.9

Evaluación electrofisiológica del sistema auditivo y vestibular

The clinical evaluation of hearing loss in adult patients is usually performed by perceptual
 assessment through audiometer tests. This evaluation requires cooperation of the evaluated
 subjects. On the other hand, it is not possible to perform a perceptual audiometer test in
 newborns, and due to the need of an early audiological management of deafness in newborns
 -with hearing aids or cochlear implants-, modern medicine requires early diagnosis of hearing
 loss, preferably before the age of three months. Several electrophysiological clinical tools have
 been developed in audiology that allow us to make early diagnosis of hearing loss in those
 who are unable to respond an audiometry. The electrophysiological evaluation of the auditory
 system includes cochlear potentials, auditory brainstem responses, and cortical auditory
 evoked potentials. On the other hand, the electrophysiological evaluation of the vestibular
 system includes the cervical and ocular myogenic vestibular potentials (cVEMPs and oVEMPs).
 This article also includes a brief description of otoacoustic emissions, which are not an electric
 measure of the central nervous system, but are widely used as a diagnostic tool in pediatric
 audiology. The physiological advances in the knowledge of the auditory system allowed the
 early diagnosis of hearing loss in the newborn. However, none of these electrophysiological
 tests replaces the perceptual evaluation of hearing thresholds with audiometric tests.

High frequency bone conduction auditory evoked potentials in the guinea pig: Assessing cochlear injury after ossicular chain manipulation

Permanent high frequency (>4 kHz) sensorineural hearing loss following middle ear surgery occurs in up to 25% of patients. The aetiology of this loss is poorly understood and may involve transmission of supra-physiological forces down the ossicular chain to the cochlea. Investigating the mechanisms of this injury using animal models is challenging, as evaluating cochlear function with evoked potentials is confounded when ossicular manipulation disrupts the normal air conduction (AC) pathway. Bone conduction (BC) using clinical bone vibrators in small animals is limited by poor transducer output at high frequencies sensitive to trauma. The objectives of the present study were firstly to evaluate a novel high frequency bone conduction transducer with evoked auditory potentials in a guinea pig model, and secondly to use this model to investigate the impact of middle ear surgical manipulation on cochlear function. We modified a magnetostrictive device as a high frequency BC transducer and evaluated its performance by comparison with a calibrated AC transducer at frequencies up to 32 kHz using the auditory brainstem response (ABR), compound action potential (CAP) and summating potential (SP). To mimic a middle ear traumatising stimulus, a rotating bur was brought in to contact with the incudomalleal complex and the effect on evoked cochlear potentials was observed. BC-evoked potentials followed the same input–output function pattern as AC potentials for all ABR frequencies. Deterioration in CAP and SP thresholds was observed after ossicular manipulation. It is possible to use high frequency BC to evoke responses from the injury sensitive basal region of the cochlea and so not rely on AC with the potential confounder of conductive hearing loss. Ongoing research explores how these findings evolve over time, and ways in which injury may be reduced and the cochlea protected during middle ear surgery.This article is part of a Special Issue entitled <IEB Kyoto>.

Corticofugal modulation of peripheral auditory responses.

The auditory efferent system originates in the auditory cortex and projects to the medial geniculate body (MGB), inferior colliculus (IC), cochlear nucleus (CN) and superior olivary complex (SOC) reaching the cochlea through olivocochlear (OC) fibers. This unique neuronal network is organized in several afferent-efferent feedback loops including: the (i) colliculo-thalamic-cortico-collicular; (ii) cortico-(collicular)-OC; and (iii) cortico-(collicular)-CN pathways. Recent experiments demonstrate that blocking ongoing auditory-cortex activity with pharmacological and physical methods modulates the amplitude of cochlear potentials. In addition, auditory-cortex microstimulation independently modulates cochlear sensitivity and the strength of the OC reflex. In this mini-review, anatomical and physiological evidence supporting the presence of a functional efferent network from the auditory cortex to the cochlear receptor is presented. Special emphasis is given to the corticofugal effects on initial auditory processing, that is, on CN, auditory nerve and cochlear responses. A working model of three parallel pathways from the auditory cortex to the cochlea and auditory nerve is proposed.

P54. New electrodes for routine intra-operative dual near-field (DNF) monitoring of the cochlear nerve

Purpose Intraoperative near-field recording of cochlear and brainstem auditory potentials (BAEP) can significantly reduce acquisition time ( Matthies and Samii, 1997 ; Moller et al., 1994 ). Over a period of 15 years we have designed and tested tympanic and brainstem electrodes to monitor the functional integrity of the lower auditory pathway (cochlea, cochlear nerve, brain stem) during surgery in the cerebello-pontine angle (CPA) and the internal auditory canal. Method For routine application, a ball-shaped design has proven to be most advantageous and was developed with a company (inomed Medizintechnik, Emmendingen, Germany). Currently, two stainless steel mini-ball electrodes are employed. One of them is connected to a stainless-steel spring reaching out of an insert earphone and attaches to the tympanic membrane (ECoG, Krieg et al., 2014 ). A second mini-ball electrode with a diameter of 1.6 mm can be placed on the cochlear nerve or at the dorsal cochlear nucleus of the brainstem to record a central auditory brainstem response (CABR). These electrodes were applied in more than 500 patients with lesions in the CPA and internal auditory canal during microsurgery. Near-field potentials have been compared to the far-field auditory brainstem response (ABR, Cz-A1/A2, band-pass 100–3000 Hz). Click stimuli were applied at 13.2 Hz. Data processing was carried out with a commercially available electrophysiological monitoring system (ISIS®, inomed). Results Electrode impedance was consistently lower than 5 kOhm at 1 kHz. Because of its ball shape, the intracranial electrode could easily be placed in the lateral recess of the fourth ventricle (dorsal cochlear nucleus, DCN) and on the cochlear nerve without having to pay attention to a specific contact area on its surface ( Fig. 1 ). If necessary, it was slid out just as easy. Waves I and II of the BAEP were best identified in recordings at the tympanic membrane, wave III to V were largest in recordings with the mini-ball electrodes at the brainstem or on the cochlear nerve. Compared to far-field ABR, amplitudes were 3–4 times larger for ECoG, and 2–20 times larger for CABR in patients with functional hearing ( Fig. 2 ). CABR was more variable than the ECoG, depending mostly on electrode location relative to the brainstem generators. With optimal placement of the electrodes, reliable BAEP averages were obtained within 40 s in far-field, and within less than 10 s in near-field recordings. Conclusions Electrodes developed for near-field recording on both ends of the cochlear nerve allow for an almost instantaneous feedback on the integrity of hearing. Dual near-field (DNF) recording is significantly superior to standard auditory far-field monitoring.

OPA1-related auditory neuropathy: site of lesion and outcome of cochlear implantation.

Hearing impairment is the second most prevalent clinical feature after optic atrophy in dominant optic atrophy associated with mutations in the OPA1 gene. In this study we characterized the hearing dysfunction in OPA1-linked disorders and provided effective rehabilitative options to improve speech perception. We studied two groups of OPA1 subjects, one comprising 11 patients (seven males; age range 13-79 years) carrying OPA1 mutations inducing haploinsufficiency, the other, 10 subjects (three males; age range 5-58 years) carrying OPA1 missense mutations. Both groups underwent audiometric assessment with pure tone and speech perception evaluation, and otoacoustic emissions and auditory brainstem response recording. Cochlear potentials were recorded through transtympanic electrocochleography from the group of patients harbouring OPA1 missense mutations and were compared to recordings obtained from 20 control subjects with normal hearing and from 19 subjects with cochlear hearing loss. Eight patients carrying OPA1 missense mutations underwent cochlear implantation. Speech perception measures and electrically-evoked auditory nerve and brainstem responses were obtained after 1 year of cochlear implant use. Nine of 11 patients carrying OPA1 mutations inducing haploinsufficiency had normal hearing function. In contrast, all but one subject harbouring OPA1 missense mutations displayed impaired speech perception, abnormal brainstem responses and presence of otoacoustic emissions consistent with auditory neuropathy. In electrocochleography recordings, cochlear microphonic had enhanced amplitudes while summating potential showed normal latency and peak amplitude consistent with preservation of both outer and inner hair cell activities. After cancelling the cochlear microphonic, the synchronized neural response seen in both normally-hearing controls and subjects with cochlear hearing loss was replaced by a prolonged, low-amplitude negative potential that decreased in both amplitude and duration during rapid stimulation consistent with neural generation. The use of cochlear implant improved speech perception in all but one patient. Brainstem potentials were recorded in response to electrical stimulation in five of six subjects, whereas no compound action potential was evoked from the auditory nerve through the cochlear implant. These findings indicate that underlying the hearing impairment in patients carrying OPA1 missense mutations is a disordered synchrony in auditory nerve fibre activity resulting from neural degeneration affecting the terminal dendrites. Cochlear implantation improves speech perception and synchronous activation of auditory pathways by bypassing the site of lesion.

Peripheral effects of the cortico-olivocochlear efferent system

The auditory efferent system comprises descending pathways from the auditory cortex to the cochlea, allowing modulation of sensory processing even at the most peripheral level. Although the presence of descending circuits that connect the cerebral cortex with olivocochlear neurons have been reported in several species, the functional role of the cortico-olivocochlear efferent system remains largely unknown. We have been studying the influence of cortical descending pathways on cochlear responses in chinchillas. Here, we recorded cochlear microphonics and auditory-nerve compound action potentials in response to tones (1–8 kHz; 30–90 dB SPL) before, during, and after auditory-cortex lidocaine or cooling inactivation (n = 20). In addition, we recorded cochlear potentials in the presence and absence of contralateral noise, before, during, and after auditory-cortex micro-stimulation (2-50 μA, 32 Hz rate) (n = 15). Both types of auditory-cortex inactivation produced changes in the amplitude of cochlear potentials. In addition, in the microstimulation experiments, we found an increase of the suppressive effects of contralateral noise in neural responses to 2–4 kHz tones. In conclusion, we demonstrated that auditory-cortex basal activity exerts tonic influences on the olivocochlear system and that auditory-cortex electrical micro-stimulation enhances the suppressive effects of the acoustic evoked olivocochlear reflex. [Work supported by FONDECYT 1120256; FONDECYT 3130635 and Fundacion Puelma.]

Electrophysiologic Consequences of Flexible Electrode Insertions in Gerbils With Noise-Induced Hearing Loss

Flexible electrode interaction with intracochlear structures in a noise-damaged region of the cochlea can lead to measureable electrophysiologic changes. An emerging goal in cochlear implantation is preservation of residual hearing subsequently allowing for combined electric and acoustic stimulation (EAS). However, residual hearing is at least partially lost in most patients as a result of electrode insertion. A gerbil model was used to examine changes to acoustically evoked cochlear potentials during simulated cochlear implantation. Gerbils were partially deafened by noise exposure to mimic residual hearing in human cochlear implant candidates. After 1 month, round window and intracochlear recordings during flexible electrode insertion were made in response to 1 kHz tone burst stimuli at 80 dB SPL. After the insertion, the cochleas were histologically examined for hair cell loss because of the noise exposure and trauma because of the electrode insertion. Anatomic damage from the flexible electrode was not observable in most cases. However, insertions caused response declines that were, on average, greater than the controls, although some losses were similar to the controls. The CM was more sensitive than the CAP for detecting cochlear disturbance. Because response reductions occurred in the absence of anatomic damage, disturbances in the fluid at the base appear to affect responses from the apex. The losses were less than in previous experiments where the basilar membrane was penetrated.

Effects of Cardiopulmonary Bypass Surgery on Auditory Function: A Preliminary Study

Hearing loss has been reported as a complication following cardiac surgery with extracorporeal circulation. Preoperative hearing testing is not commonly done in these procedures, so preoperative and postoperative hearing loss, if any, may occur unnoticed. 30 subjects in the age range of 50–70 with a mean age of 60.16 years with myocardial infarction and scheduled to undergo cardiopulmonary bypass surgery underwent detailed audiological assessment comprising of pure tone audiometry with extended high frequency audiometry, speech audiometry and otoacoustic emissions (OAE) testing. The audiological testing was done preoperatively and at 2 weeks after the surgery. On pure tone audiometry, the difference between pre- and postsurgery mean values for both ears at 10, 12, and 16 KHz showed highly significant differences (P < 0.0001). On OAE testing, a significant difference (P < 0.05) between pre- and postvalues of signal to noise ratio (SNR) was found. It is hypothesised that CPB surgery makes blood redistribution to other organs easy, deviating from internal ear, which is highly susceptible as it lacks collateral circulation and its cells have high energy metabolism. Epithelial damage on internal ear microcirculation causes reduction of the cochlear potentials and hence hearing loss.

O3-E-20. Intraoperative cochlear nerve mapping by cochlear nerve action potential

Methods for intraoperative mapping of the cochlear nerve (CN) in surgery for acoustic neurinoma (AN) have not yet been established. We attempted intraoperative mapping of the cochlear nerve by cochlear nerve action potential (CNAP) with a new recording probe. The subjects were 10 patients who had undergone surgery for AN using a retrosigmoid approach. Three of the 10 patients had severe hearing impairment so that CNAP data could not be obtained. In six of seven patients with useful hearing acuity, CN could be identified during surgery. However, CNAP was obtained in the nerves adjacent to CN. We could identify CN by the difference in waveforms between CN and the adjacent nerves. The recording probe was appropriate for mapping, but was inappropriate for functional monitoring. In contrast, conventional electrodes were more suitable for functional monitoring, but were not suitable for mapping. The combination of these electrode types would greatly improve the accuracy of monitoring. We performed CNAP by monopolar and bipolar recording. In bipolar recordings, the signal to noise ratio was higher than that in the monopolar recordings. The combination of monopolar and bipolar recordings would also improve the accuracy of monitoring.

Intraoperative Round Window Recordings to Acoustic Stimuli From Cochlear Implant Patients

Acoustically evoked neural and hair cell potentials can be measured from the round window (RW) intraoperatively in the general population of cochlear implant recipients. Cochlear implant performance varies greatly among patients. Improved methods to assess and monitor functional hair cell and neural substrate before and during implantation could potentially aid in enhanced nontraumatic intracochlear electrode placement and subsequent improved outcomes. Subjects (1-80 yr) undergoing cochlear implantation were included. A monopolar probe was placed at the RW after surgical access was obtained. The cochlear microphonic (CM), summating potential (SP), compound action potential (CAP), and auditory nerve neurophonic (ANN) were recorded in response to tone bursts at frequencies of 0.25 to 4 kHz at various levels. Measurable hair cell/neural potentials were detected to 1 or more frequencies in 23 of 25 subjects. The greatest proportion and magnitude of cochlear responses were to low frequencies (<1,000 Hz). At these low frequencies, the ANN, when present, contributed to the ongoing response at the stimulus frequency. In many subjects, the ANN was small or absent, whereas hair cell responses remained. In cochlear implant recipients, acoustically evoked cochlear potentials are detectable even if hearing is extremely limited. Sensitive measures of cochlear and neural status can characterize the state of hair cell and neural function before implantation. Whether this information correlates with speech performance outcomes or can help in tailoring electrode type, placement or audiometric fitting, can be determined in future studies.

Acute hyperfibrinogenemia impairs cochlear blood flow and hearing function in guinea pigs in vivo

Objective: Impairment of microcirculation is a possible cause of sudden sensorineural hearing loss (SSNHL). Fibrinogen is known as a risk factor for both microvascular dysfunction and SSNHL. Therefore, the aim of this study was to investigate the effect of elevated serum levels of fibrinogen on cochlear blood flow and hearing function in vivo. Design: One group of guinea pigs received two consecutive injections of 100 mg fibrinogen while a control group received equimolar doses of albumin. Measurements of cochlear microcirculation by intravital microscopy and of hearing thresholds by auditory brainstem response (ABR) recordings were carried out before, after first and after second injection. Study sample: Ten healthy guinea pigs were randomly assigned to a treatment group or a control group of five animals each. Results: Serum fibrinogen levels were elevated after the first and second injections of fibrinogen compared to basal values and control group respectively. Increasing levels of fibrinogen were paralleled by decreasing cochlear blood flow as well as increasing hearing thresholds. Hearing threshold correlated negatively with cochlear blood flow. Conclusions: The effect of microcirculatory impairment on hearing function could be explained by a malfunction of the cochlear amplifier. Further investigation is needed to quantify cochlear potentials under elevated serum fibrinogen levels.

Detection of intracochlear damage during cochlear implant electrode insertion using extracochlear measurements in the gerbil

An intraoperative monitoring algorithm during cochlear implant electrode insertion could be used to detect trauma and guide electrode placement relative to surviving hair cells. The aim of this report was to assess the feasibility of using extracochlear recording sites to monitor acoustically evoked responses from surviving hair cells and neural elements during implantation in an animal model. Animal experiments. The normal-hearing gerbil was used. Two recording methods, one using a lock-in amplifier and another using Fourier analysis of recorded signals, were used to obtain frequency-specific information about the responses to tones. Amplitude and threshold determinations were made at the round window and at three extracochlear sites. To induce intracochlear damage, a platinum-iridium wire was inserted through the round window. The wire was advanced, and changes in the potentials were correlated with cochlear contact. Anatomic integrity was assessed using cochlea whole mount preparations. In general, the lock-in amplifier showed greater sensitivity and lower thresholds at higher frequencies relative to the Fourier method. Also, the lock-in amplifier was more resistant to masking effects. Both systems were able to detect loss of cochlear potentials secondary to intracochlear trauma. Histologic damage was seen in all cases and corresponded to electrophysiologic changes. Impact of electrodes on cochlear structures affecting cochlear performance could be detected from several extracochlear sites. The lock-in amplifier demonstrated greater sensitivity and resistance to noise when compared to the fast Fourier transform recording paradigm. The latter showed greater flexibility of detecting and separating hair cell and neural potentials.

Effect of the High Potassium Ion in the Perilymphatic Spase on the Cochlear Potentials

Effect of the High Potassium Ion in the Perilymphatic Spase on the Cochlear Potentials

Effect of Temperature Change on the Cochlear Potentials of the Guinea Pig

Effect of Temperature Change on the Cochlear Potentials of the Guinea Pig

W3.4 Intraoperative observation of changes in cochlear nerve action potentials during exposure to electromagnetic fields generated by mobile phones

W3.4 Intraoperative observation of changes in cochlear nerve action potentials during exposure to electromagnetic fields generated by mobile phones

Effects of Electrical Stimulation of Olivocochlear Fibers in Cochlear Potentials in the Chinchilla

The mammalian cochlea has two types of sensory cells; inner hair cells, which receive auditory-nerve afferent innervation, and outer hair cells, innervated by efferent axons of the medial olivocochlear (MOC) system. The role of the MOC system in hearing is still controversial. Recently, by recording cochlear potentials in behaving chinchillas, we suggested that one of the possible functions of the efferent system is to reduce cochlear sensitivity during attention to other sensory modalities (Delano et al. in J Neurosci 27:4146-4153, 2007). However, in spite of these compelling results, the physiological effects of electrical MOC activation on cochlear potentials have not been described in detail in chinchillas. The main objective of the present work was to describe these efferent effects in the chinchilla, comparing them with those in other species and in behavioral experiments. We activated the MOC efferent axons in chinchillas with sectioned middle-ear muscles by applying current pulses at the fourth-ventricle floor. Auditory-nerve compound action potentials (CAP) and cochlear microphonics (CM) were acquired in response to clicks and tones of several frequencies, using a round-window electrode. Electrical efferent stimulation produced CAP amplitude suppressions reaching up to 11dB. They were higher for low to moderate sound levels. Additionally, CM amplitude increments were found, the largest (≤ 2.5dB) for low intensity tones. CAP suppression was present at all stimulus frequencies, but was greatest for 2kHz. CM increments were highest for low-frequency tones, and almost absent at high frequencies. We conclude that the effect obtained in chinchilla is similar to but smaller than that observed in cats, and that the effects seen in awake chinchillas, albeit different in magnitude, are consistent with the activation of efferent fibers.

Presynaptic and postsynaptic mechanisms underlying auditory neuropathy in patients with mutations in theOTOForOPA1gene

AbstractObjective: Our objective was to compare acoustically- and electrically-evoked potentials of the auditory nerve in patients with postsynaptic or presynaptic auditory neuropathy with underlying mutations in the OPA1 or OTOF gene. Study design: Transtympanic electrocochleography (ECochG) was recorded from two adult patients carrying the R445H OPA1 mutation, and from five children with mutations in the OTOF gene. Cochlear potentials to clicks or tone-bursts were compared to recordings obtained from 16 normally hearing subjects. Electrically-evoked neural responses recorded through the cochlear implant were also obtained. Results: The cochlear microphonic (CM) was recorded from all subjects, with normal amplitudes. After cancelling the CM, cochlear potentials were of negative polarity with reduced amplitude and prolonged duration compared to controls in both groups of patients. Prolonged negative responses were recorded as low as 50–90dB below behavioural threshold in subjects with OTOF mutations where...

Using the Cochlear Microphonic as a Tool to Evaluate Cochlear Function in Mouse Models of Hearing

The cochlear microphonic (CM) can be a useful analytical tool, but many investigators may not be fully familiar with its unique properties to interpret it accurately in mouse models of hearing. The purpose of this report is to develop a model for generation of the CM in wild-type (WT) and prestin knockout mice. Data and modeling results indicate that in the majority of cases, the CM is a passive response, and in the absence of outer hair cell (OHC) damage, mice lacking amplification are expected to generate WT levels of CM for inputs less than approximately 30 kHz. Hence, this cochlear potential is not a useful metric to estimate changes in amplifier gain. This modeling analysis may explain much of the paradoxical data in the literature. For example, various manipulations, including the application of salicylate and activation of the crossed olivocochlear bundle, reduce the compound action potential but increase or do not change the CM. Based on this current evaluation, CM measurements are consistent with early descriptions where this AC cochlear potential is dominated by basal OHCs, when recorded at the round window.