Cochlear Potentials Research Articles

A superior semicircular canal dehiscence-induced air-bone gap in chinchilla

An SCD is a pathologic hole (or dehiscence) in the bone separating the superior semicircular canal from the cranial cavity that has been associated with a conductive hearing loss in patients with SCD syndrome. The conductive loss is defined by an audiometrically determined air-bone gap that results from the combination of a decrease in sensitivity to air-conducted sound and an increase in sensitivity to bone-conducted sound. Our goal is to demonstrate, through physiological measurements in an animal model, that mechanically altering the superior semicircular canal (SC) by introducing a hole (dehiscence) is sufficient to cause such an air-bone gap. We surgically introduced holes into the SC of chinchilla ears and evaluated auditory sensitivity (cochlear potential) in response to both air- and bone-conducted stimuli. The introduction of the SC hole led to a low-frequency (<2000 Hz) decrease in sensitivity to air-conducted stimuli and a low-frequency (<1000 Hz) increase in sensitivity to bone-conducted stimuli resulting in an air-bone gap. This result was consistent and reversible. The air-bone gaps in the animal results are qualitatively consistent with findings in patients with SCD syndrome.

Information from cochlear potentials and genetic mutations helps localize the lesion site in auditory neuropathy

Auditory neuropathy (AN) is a disorder characterized by disruption of auditory nerve activity resulting from lesions involving the auditory nerve (postsynaptic AN), inner hair cells and/or the synapses with auditory nerve terminals (presynaptic AN). Affected subjects show impairment of speech perception beyond that expected for the hearing loss, abnormality of auditory brainstem potentials and preserved outer hair-cell activities. Furthermore, AN can be identified either as an isolated disorder or as an associated disorder with multisystem involvement including peripheral and optic neuropathies (non-isolated AN). Mutations in several nuclear and mitochondrial genes have been identified as underlying these forms of AN. Recently, new genes have been identified as involved in both isolated (DIAPH3, OTOF) and non-isolated AN (OPA1). Moreover, abnormal cochlear potentials have been recorded from patients with specific gene mutations by using acoustic stimuli or electrical stimulation through cochlear implant. In this review, different types of genetically based auditory neuropathies are discussed and the proposed molecular mechanisms underlying AN are reviewed.

Post exposure administration of A 1 adenosine receptor agonists attenuates noise-induced hearing loss

Adenosine is a constitutive cell metabolite with a putative role in protection and regeneration in many tissues. This study was undertaken to determine if adenosine signalling pathways are involved in protection against noise injury. A 1 adenosine receptor expression levels were altered in the cochlea exposed to loud sound, suggesting their involvement in the development of noise injury. Adenosine and selective adenosine receptor agonists (CCPA, CGS-21680 and Cl-IB-MECA) were applied to the round window membrane of the cochlea 6 h after noise exposure. Auditory brainstem responses measured 48 h after drug administration demonstrated partial recovery of hearing thresholds (up to 20 dB) in the cochleae treated with adenosine (non-selective adenosine receptor agonist) or CCPA (selective A 1 adenosine receptor agonist). In contrast, the selective A 2A adenosine receptor agonist CGS-21680 and A 3 adenosine receptor agonist Cl-IB-MECA did not protect the cochlea from hearing loss. Sound-evoked cochlear potentials in control rats exposed to ambient noise were minimally altered by local administration of the adenosine receptor agonists used in the noise study. Free radical generation in the cochlea exposed to noise was reduced by administration of adenosine and CCPA. This study pinpoints A 1 adenosine receptors as attractive targets for pharmacological interventions to reduce noise-induced cochlear injury after exposure.

A visual cue modulates the firing rate and latency of auditory-cortex neurons in the chinchilla

We studied single and multi-unit activity recorded with tetrodes, from the left auditory cortex of awake chinchillas while they performed a frequency discrimination task. Auditory stimuli were preceded by a silent visual cue. We examined firing rates and first-spike latencies of 181 units in the presence and absence of the visual cue. To discard possible auditory artifacts produced by the visual cue, cochlear potentials were simultaneously recorded by an electrode positioned at the round window of the right cochlea. We found that the visual stimulus altered the firing rate and the mean first-spike latency of 9% and 18% of the recorded auditory-cortex cells, respectively. Furthermore, we found that the subset of neurons in which the firing rate was modulated by the visual cue was distinct from the subset of neurons that changed their latency in the presence of the visual cue. Adding both groups, a visual-stimulus modulated the firing characteristics of 27% of the recorded auditory-cortex neurons in the awake chinchilla. Our results imply that in the auditory cortex, latency and firing rate can be independently altered by visual stimuli, and that both types of analysis must be considered in order to fully understand neural cross-modal interactions.

Mutation of OPA1 gene causes deafness by affecting function of auditory nerve terminals

Autosomal dominant optic atrophy (DOA) is a retinal neuronal degenerative disease characterized by a progressive bilateral visual loss. We report on two affected members of a family with dominantly inherited neuropathy of both optic and auditory nerves expressed by impaired visual acuity, moderate pure tone hearing loss, and marked loss of speech perception. We investigated cochlear abnormalities accompanying the hearing loss and the effects of cochlear implantation. We sequenced OPA1 gene and recorded cochlear receptor and neural potentials before cochlear implantation. Genetic analysis identified R445H mutation in OPA1 gene. Audiological studies showed preserved cochlear receptor outer hair cell activities (otoacoustic emissions) and absent or abnormally delayed auditory brainstem responses (ABRs). Trans-tympanic electrocochleography (ECochG) showed prolonged low amplitude negative potentials without auditory nerve compound action potentials. The latency of onset of the cochlear potentials was within the normal range found for inner hair cell summating receptor potentials. The duration of the negative potential was reduced to normal during rapid stimulation consistent with adaptation of neural sources generating prolonged cochlear potentials. Both subjects had cochlear implants placed with restoration of hearing thresholds, speech perception, and synchronous activity in auditory brainstem pathways. The results suggest that deafness accompanying this OPA1 mutation is due to altered function of terminal unmyelinated portions of auditory nerve. Electrical stimulation of the cochlea activated proximal myelinated portions of auditory nerve to restore hearing.

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.

Function of the sexually dimorphic ear of the American bullfrog,Rana catesbeiana: brief review and new insight

The dimorphic ear of the bullfrog, Rana catesbeiana, has long been enigmatic. The male's tympanic membrane (TM) area approximates twice the area of the female's; however, similar size differences in the area of the columellar footplate were not observed between the sexes. Hence, the male's hearing is expected to be more sensitive than the female's but this is not the case. Asking what offsets the advantage of the large TM, we applied a series of experiments to the auditory system. Male and female audiograms based on stimulation with airborne sound and on both multi-unit responses from the brain and alternating cochlear potentials ('microphonics') showed equal sensitivity and a small difference in frequency response; at low frequencies the male was more sensitive than the female. Amputating the columella and stimulating the stump with mechanical vibration showed that for an equal microphonic response, the male's footplate vibrated with lower amplitude than the female's footplate. Mechanically stimulating the TM of the intact ear replicated this result, excluding the involvement of the mechanical lever. The TM of the male weighs five times the TM of the female, and artificial loading of the TM of either sex greatly reduced the ear's sensitivity. Hence, the male's excessive area ratio (TM to columellar footplate) is offset by the heavier cartilage cushion on the male's TM, damping the TM's response to sound. This is corroborated by experimentally artificially loading the TM. The product of area ratio and footplate vibration amplitude would result in similar stimulation of the inner ear in the two sexes.

Slow build-up of cochlear suppression during sustained contralateral noise: Central modulation of olivocochlear efferents?

The strength of the medial olivocochlear (OC) reflex is routinely assayed by measuring suppression of ipsilateral responses such as otoacoustic emissions (OAEs) by a brief contralateral noise, e.g., (Berlin, C.I., Hood, L.J., Cecola, P., Jackson, D.F., Szabo, P. 1993. Does type I afferent dysfunction reveal itself through lack of efferent suppression. Hear. Res. 65, 40–50). Here, we show in anesthetized guinea pigs, that the magnitude of OC-mediated suppression of ipsilateral cochlear responses (i.e., compound actions potentials (CAPs), distortion product (DP) OAEs and round-window noise) slowly builds over 2–3 min during a sustained contralateral noise. The magnitude of this build-up suppression was largest at low ipsilateral stimulus intensities, as seen for suppression measured at contra-noise onset. However, as a function of stimulus frequency, build-up suppression magnitude was complementary to onset suppression, i.e., largest at the lowest and highest frequencies tested. Both build-up and onset suppression were eliminated by cutting the OC bundle. In contrast to “slow effects” of shock-evoked medial OC activity (Sridhar, T.S., Liberman, M.C., Brown, M.C., Sewell, W.F. 1995. A novel cholinergic “slow effect” of efferent stimulation on cochlear potentials in the guinea pig. J. Neurosci. 15, 3667–3678), which are mediated by slow intracellular changes in Ca concentration in OHCs, build-up effects of contralateral noise are immediately extinguished upon OC bundle transection and are likely mediated by central modulation of the response rates in MOC fibers due to the sustained noise. Results suggest that conventional tests of OC reflex strength may underestimate its magnitude in noisy environments.

Comment on “When an Air-Bone Gap is not a Sign of a Middle-Ear Conductive Loss” By Sohmer et al.

Comment on “When an Air-Bone Gap is not a Sign of a Middle-Ear Conductive Loss” By Sohmer et al.

Cochlear microphonic audiometry: a new hearing test for objective diagnosis of deafness

Conclusions. Objective audiometric tests could constitute a valuable tool for detection of deafness. This could be especially useful in children (universal newborn hearing screening) and non-collaborative patients, who are especially difficult candidates for classic audiometry. The cochlear microphonic audiometry (CMA) technique offers the possibility of obtaining objective audiometric profiles, highly correlated with those obtained by pure tone audiometry (PTA). Therefore, CMA could be used as an alternative test to obtain the audiometric profile of these patients. Objective. The main purpose of the present study was to demonstrate that CMA provides objective audiometric profiles by avoiding active participation by the patient. Subjects and methods. CMA specific equipment, improved for non-invasive recording of cochlear microphonic potentials, was used. This tool plots the recordings obtained as the classic audiogram. Verification of the method was carried out in adult patients by comparing the PTA with the CMA audiometric profiles obtained for each patient. Results. Our findings showed that audiometric profiles obtained from CMA are highly correlated, without statistical differences, to those obtained with PTA. More than 81% of patients explored (91.67% at 250 Hz) exhibited differences below 10 dB(HL) between tests at all exploration frequencies, while a low number of cases showed differences over 20 dB(HL).

L’ischémie cochléaire : des données fondamentales aux espoirs cliniques

Objectives To report the known data on the functional consequences of cochlear ischemia and the tools available to detect them. Methods Review of the main integrated in vivo models described in mammals. Results The main integrated models of cochlear ischemia use laser doppler velocimetry to measure the degree of ischemia. Cochlear function can be effectively monitored during cochlear ischemia through the cochlear potentials and otoacoustic emissions, each of these signals giving specific information. The cochlea appears to be particularly resistant to several minutes of reversible ischemia. Indirect monitoring of cochlear ischemia can be achieved through distortion-product otoacoustic emissions during surgical procedures to the cerebellopontine angle. It is still impossible to directly and noninvasively detect cochlear ischemia in nonsurgical clinical practice. Conclusions Integrated models of cochlear ischemia have contributed greatly to our knowledge of the functional behavior of the cochlea in this specific situation. Clinical practice now needs to be able to detect cochlear ischemia early and noninvasively, for example in cases of sudden hearing loss.

Neural and receptor cochlear potentials obtained by transtympanic electrocochleography in auditory neuropathy

Objective Transtympanic electrocochleography (ECochG) was recorded bilaterally in children and adults with auditory neuropathy (AN) to evaluate receptor and neural generators. Methods Test stimuli were clicks from 60 to 120 dB p.e. SPL. Measures obtained from eight AN subjects were compared to 16 normally hearing children. Results Receptor cochlear microphonics (CMs) in AN were of normal or enhanced amplitude. Neural compound action potentials (CAPs) and receptor summating potentials (SPs) were identified in five AN ears. ECochG potentials in those ears without CAPs were of negative polarity and of normal or prolonged duration. We used adaptation to rapid stimulus rates to distinguish whether the generators of the negative potentials were of neural or receptor origin. Adaptation in controls resulted in amplitude reduction of CAP twice that of SP without affecting the duration of ECochG potentials. In seven AN ears without CAP and with prolonged negative potential, adaptation was accompanied by reduction of both amplitude and duration of the negative potential to control values consistent with neural generation. In four ears without CAP and with normal duration potentials, adaptation was without effect consistent with receptor generation. In five AN ears with CAP, there was reduction in amplitude of CAP and SP as controls but with a significant decrease in response duration. Conclusions Three patterns of cochlear potentials were identified in AN: (1) presence of receptor SP without CAP consistent with pre-synaptic disorder of inner hair cells; (2) presence of both SP and CAP consistent with post-synaptic disorder of proximal auditory nerve; (3) presence of prolonged neural potentials without a CAP consistent with post-synaptic disorder of nerve terminals. Significance Cochlear potential measures may identify pre- and post-synaptic disorders of inner hair cells and auditory nerves in AN.

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.

A mechano-acoustic model of the effect of superior canal dehiscence on hearing in chinchilla

Superior canal dehiscence (SCD) is a pathological condition of the ear that can cause a conductive hearing loss. The effect of SCD (a hole in the bony wall of the superior semicircular canal) on chinchilla middle- and inner-ear mechanics is analyzed with a circuit model of the dehiscence. The model is used to predict the effect of dehiscence on auditory sensitivity and mechanics. These predictions are compared to previously published measurements of dehiscence related changes in chinchilla cochlear potential, middle-ear input admittance and stapes velocity. The comparisons show that the model predictions are both qualitatively and quantitatively similar to the physiological results for frequencies where physiologic data are available. The similarity supports the third-window hypothesis of the effect of superior canal dehiscence on auditory sensitivity and mechanics and provides the groundwork for the development of a model that predicts the effect of superior canal dehiscence syndrome on auditory sensitivity and mechanics in humans.

Gender as a Predictor of Hearing Preservation Outcome in Acoustic Neuroma Surgery

Introduction: The correlation between gender and likelihood of preservation of serviceable postoperative hearing in acoustic neuroma surgery has seldom been reported. The limited available data suggest that, when preoperative tumor size and hearing are comparable, males have a greater likelihood of preservation of some postoperative hearing (p < 0.05 at best). Methods: A consecutive series of 184 retrosigmoid procedures for removal of unilateral acoustic neuromas (AN), in the period ending June 30, 2005, were subjected retrospectively to linear regression analysis for factors predictive of successful postoperative preservation of Gardner and Robertson Class 1 and 2 hearing (HP). These cases were selected on the basis of size (mean extracanalicular diameter < 20 mm) and preoperative hearing, and form part of a larger series of 810 consecutive cases of unilateral AN. Variables examined included age, gender, side and size of tumor, preoperative hearing, and intraoperative cochlear nerve compound action potential (CAP) threshold shift. Results: Overall HP rate was 34.4% (53.8% for intracanalicular AN). Size (p < 0.001), intraoperative CAP threshold shift (p < 0.0001), and female gender (p = 0.01) were predictors of HP. Male-female ratio for the series was 47/53. Age (p = 0.37) and tumor size (p = 0.20) did not differ between males and females. Postoperative HP occurred in 25.4% of males and 44.2 % of females, respectively (p = 0.01). Conclusions: Though female gender has not previously been identified as a predictor of greater likelihood of preservation of serviceable postoperative hearing in AN surgery, the present study strongly suggests that this is the case. Gender difference should probably be taken into account in preoperative discussion of outcome, at least in our hands, and may have other implications as well.

Evoked cochlear potentials in the barn owl

Gross electrical responses to tone bursts were measured in adult barn owls, using a single-ended wire electrode placed onto the round window. Cochlear microphonic (CM) and compound action potential (CAP) responses were evaluated separately. Both potentials were physiologically vulnerable. Selective abolishment of neural responses at high frequencies confirmed that the CAP was of neural origin, while the CM remained unaffected. CAP latencies decreased with increasing stimulus frequency and CAP amplitudes were correlated with known variations in afferent fibre numbers from the different papillar regions. This suggests a local origin of the CAP along the tonotopic gradient within the basilar papilla. The audiograms derived from CAP and CM threshold responses both showed a broad frequency region of optimal sensitivity, very similar to behavioural and single-unit data, but shifted upward in absolute sensitivity. CAP thresholds rose above 8 kHz, while CM responses showed unchanged sensitivity up to 10 kHz.

Electrophysiological measurement method and system for positioning an implantable, hearing instrument transducer

An electrophysiological measurement method and system is provided for positioning an implantable transducer of a hearing instrument relative to a middle ear component or inner ear of a patient. The method and system employ electrophysiological measurement signals obtained in response to test signals applied to an implanted transducer. In one embodiment, the electrophysiological measurements are obtained by an electrocochleography measurement device that measures the cochlear summating potential and/or action potential responsive to test signals applied to an implanted transducer. In another embodiment, an auditory brainstem response measurement device is utilized to obtain electrical potential measurement signals responsive to test signals applied to an implanted transducer.

Columella footplate motion and the cochlear microphonic potential in the embryo and hatchling chicken

A piezoelectric (PZE) vibrator was used to mechanically drive the columella footplate and stimulate the cochlea of chicken embryos and hatchlings. Our objectives were to characterize the motion of the PZE driver and determine the relationship between columella footplate motion (displacement/ velocity) and the cochlear microphonic recorded from the recessus scala tympani (CMrst). At each frequency, displacement of the PZE driver probe tip was linearly related to the applied voltage over a wide range of attenuation levels (-60 to -20 dBre:50 Vp-p). The mean displacement across frequencies (100-4000 Hz) was 0.221+/-0.042 micromp-p for a constant applied voltage level of -20 dBre:50 Vp-p. Displacement was within 1.5 dB of the mean for this stimulus level at all frequencies except for 4000 Hz, where it was approximately 3 dB higher (p < 0.01). CMrst amplitudes in hatchlings were larger than amplitudes in embryos (p=0.003). For a given frequency, CM was linearly related to footplate displacement and velocity at both ages. The transform ratio of CMrst/A (CM amplitude/displacement) increased at approximately 6 dB/octave at frequencies between 100 and 1000 Hz in hatchlings suggesting that cochlear impedance (Zc) was resistive at these frequencies. In a large fraction of the embryos, Zc exhibited reactive behavior.

Effects of nimodipine, an L-type calcium channel antagonist, on the chicken’s cochlear potentials

At most synapses in the brain, neurotransmitter release depends on N-type or P/Q-type calcium channels. However, available in vitro experimental data suggest that there exist almost exclusively L-type calcium channels in sensory hair cells of most species. To test whether chicken hair cells depend on L-type calcium channels for neurotransmitter release, we examined the effects of nimodipine, a selective L-type calcium channel antagonist, on acoustically evoked cochlear potentials in 10–15 week old chickens in vivo. Diffusion of nimodipine into scala tympani significantly elevated threshold, dramatically decreased the amplitude and increased the latency of the compound action potential within 20 min of drug application. The summating potential was also significantly reduced in amplitude, but the cochlear microphonic was relatively less affected. All the effects were reversible after nimodipine was washed out with artificial perilymph except that the cochlear microphonic amplitude remained decreased. Application of omega-conotoxin GVIA, an N-type calcium channel antagonist and agatoxin Tk, a P-type calcium channel antagonist had no observable effects on the cochlear potentials. These results suggest that L-type calcium channels control neurotransmitter release from avian hair cells.

Inferior colliculus stimulation causes similar efferent effects on ipsilateral and contralateral cochlear potentials in the guinea pig

The inferior colliculus (IC) is a processing center in both the ascending and descending auditory pathways. It has been demonstrated anatomically to send descending projections to the region of the medial olivocochlear (MOC) neurons in the auditory brainstem. Activation of MOC system produces reductions in cochlear neural activity. Individual MOC fibers innervate relatively restricted regions of the cochlea. Recent studies have shown that selective electrical stimulation within the IC central nucleus (ICC) produces frequency-specific reductions of neural activity in the contralateral cochlea (Ota, Y., Oliver, D.L., Dolan, D.F., 2004. Frequency-specific effects on cochlear responses during activation of the inferior colliculus in the guinea pig. J. Neurophysiol. 91, 2185–2193). This efferent effect is likely mediated through selective activation of MOC cells. In this study, we investigated the effects of selective stimulation of one ICC on cochlear output in both ears in anesthetized and paralyzed guinea pigs to explore possible differences in the effective efferent innervation of the two ears. ICC stimulation had a similar tonotopically tuned effect on the distortion product otoacoustic emission (DPOAE) and the cochlear whole-nerve action potential (CAP) in each cochlea. The bandwidth of the efferent effect in each ear was measured and compared at different stimulation levels. For a given ICC stimulation site, the efferent effects were larger for the CAP response. The effect on each response measure was greater in the contralateral than the ipsilateral ear. The effective bandwidth of the efferent effect on the CAP was current-level-dependent but less so for the DPOAE. The results of transections at various locations within the brainstem suggest that the effects were mediated by the MOC system. From the results presented here, the descending efferent system, which originates in the auditory cortex, has frequency-specific, spatially restricted, bilateral effects. The effects are greater in the contralateral ear.