Rozprawy doktorskie na temat „Electrocochleography”

Distortion-product emissions (DPEs) are tonal responses that may be detected in the ear canal when the ear is stimulated simultaneously by two tones that are closely spaced in frequency. In experimental animals, DPEs are reduced in amplitude or are eliminated when cochlear function is disrupted. This association has not been investigated in human subjects. This study was designed to investigate the relation of cochlear status, as determined by pure-tone behavioral thresholds, to DPE amplitude in human subjects. Forty men were selected as subjects. Twenty had normal hearing and 20 had high-frequency sensorineural hearing loss. Pure-tone behavioral thresholds were determined using conventional audiometric procedures for eight frequencies from 750 to 8000 Hz. DPEs were generated in the test ear of each subject by stimulating the ear with two tones, f1 and f2. The stimuli were selected to approximate audiometric test frequencies. Responses were detected by a sensitive microphone that was placed in the ear canal and were extracted by spectral analysis. Results of the study indicated that DPE amplitude was associated with pure-tone threshold. When audiometric threshold was ≤10 dB HL, DPEs could be elicited at all test frequencies for 98% of subjects in both groups. Mean maximum emission amplitude ranged from 3 to 13 dB SPL across frequency. When pure-tone threshold was above 50 dB HL, DPEs were absent or were significantly attenuated. DPEs varied in amplitude when audiometric threshold was between these two extremes. The association of DPE amplitude were pure-tone threshold was frequency specific. DPE amplitude was maximal when pure-tone thresholds were ≤10 dB HL and decreased as pure-tone behavioral threshold increased in the same subject. Repetition of the DPE protocol with five subjects from each group during separate test sessions indicated that the results were reliable over time. Results of the study have clinical implications. The technique may have potential as a noninvasive means of monitoring the status of the cochlea in human subjects.

Ménière’s disease (MD) is an idiopathic inner ear disorder, characterised by episodes of vertigo, tinnitus, sensorineural hearing loss, and aural fullness in the affected ear. The relatively high variability of symptomological changes renders it difficult to confirm the MD diagnosis. The purpose of this study is to compare the diagnostic power of an instrumental method, electrocochleography (ECochG), and two subjective methods, including the criteria based on the clinical guidelines provided by the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing Equilibrium (AAO-HNS CHE) and Gibson’s Score. A quota sampling method was used to include subjects. A total of 250 potential MD patients who were referred to the Department of Otolaryngology at the Christchurch Hospital between year 1994 and 2009 have had their signs and symptoms documented and ECochG testing completed. A selection of details obtained from both AAO-HNS CHE and ECochG assessment results were examined as a chart review in regard to its function as a diagnostic tool for MD. The between-method reliability was found to be high, with a few disagreements on individual diagnosis. Based on a receiver operating characteristic (ROC) curve analysis, the ECochG measures were shown to be pertinent to the diagnosis of MD. It was also found that patients tested “positive”, as compared with those tested “negative”, tended to show higher correlations among the four key symptoms of MD and among the ECochG measures derived from the auditory evoked responses to tone bursts at frequencies in close proximity to each other.

[Truncated abstract] The cochlea presumably possesses a number of regulatory mechanisms to maintain cochlear sensitivity in the face of disturbances to its function. Evidence for such mechanisms can be found in the time-course of the recovery of CAP thresholds during experimental manipulations, and in observations of slow oscillations in cochlear micromechanics following exposure to low-frequency tones (the “bounce phenomenon”) and other perturbations. To increase our understanding of these oscillatory processes within the cochlea, and OHCs in particular, investigations into cochlear regulation were carried out using a combination of mathematical modelling of the ionic and mechanical interactions likely to exist within the OHCs, and electrophysiological experiments conducted in guinea pigs. The electrophysiological experiments consisted of electrocochleographic recordings and, in some cases, measurement of otoacoustic emissions, during a variety of experimental perturbations, including the application of force to the cochlear wall, exposure to very-low-frequency tones, injection of direct current into scala tympani, and intracochlear perfusions of artificial perilymph containing altered concentrations of potassium, sodium, and sucrose. To obtain a panoramic view of cochlear regulation under these conditions, software was written to enable the interleaved and near-simultaneous measurement of multiple indicators of cochlear function, including the compound action potential (CAP) threshold, amplitude and waveshape at multiple frequencies, the OHC transfer curves derived from low-frequency cochlear microphonic (CM) waveforms, distortion-product otoacoustic emissions (DPOAEs), the spectrum of the round-window neural noise (SNN), and the endocochlear potential (EP). ... The mathematical model we have developed provided a physiologically-plausible and internally-consistent explanation for the time-courses of the cochlear changes observed during a number of different perturbations. We show that much of the oscillatory behaviour within the cochlea is consistent with underlying oscillations in cytosolic calcium concentration. We conclude that a number of the discrepancies between the simulation results and the experimental data can be resolved if the cytosolic calcium functions as two distinct pools: one which controls basolateral permeability and one which controls slow motility. This two-calcium-pool model is discussed.

The acoustic reflex refers to the contraction of a middle ear muscle in response to sound. The contraction causes a stiffening of the middle ear system and, consequently, the flow of acoustic energy to the cochlea is impeded. By measuring the change in admittance in the auditory system during sound stimulation it is possible to indirectly monitor the middle ear muscle contractions. Such measurements provide useful information regarding the integrity of the auditory system and the location of the auditory pathology.

[Truncated abstract] The mammalian inner ear is innervated by the efferent olivocochlear system which is divided into medial and lateral systems. In anaesthetised animals, medial olivocochlear (MOC) axons can be electrically stimulated at the floor of the IVth ventricle. MOC stimulation suppresses the spontaneous activity and sound-evoked responses of primary afferents by its actions on outer hair cells. Effects of MOC stimulation have been also reported on responses of neurons in the cochlear nucleus, the first central auditory center receiving cochlear input. However, very little is known about the net results of MOC effects in higher order neurons. This issue was investigated by electrically stimulating MOC axons at the IVth ventricle and recording extracellular single unit activities in the central nucleus of the inferior colliculus (CNIC) of anaesthetised guinea pigs. For the first part of the study, anatomical and neurophysiological studies were carried out to establish that the focal midline MOC stimulation can selectively stimulate MOC axons without any current spread to adjacent ascending fibers. The MOC stimulation and CNIC recordings were then carried out in a series of experiments that included normal hearing animals, animals treated acutely with gentamicin (in which the acetylcholine-mediated peripheral suppression of the olivocochlear efferents is selectively eliminated) and partially deafened animals. ... However, in other CNIC neurons, effects could not be so explained, showing either additional suppression or even marked excitatory effects. (4) MOC stimulation also suppressed the spontaneous activity of CNIC neurons in normal hearing animals. When similar efferent stimulation was carried out in partially deafened animals, the abnormally high spontaneous activity of some CNIC neurons in the deafened frequency regions was also transiently suppressed by MOC shocks. The results from this study clearly demonstrate that the MOC system can modulate the responses of midbrain neurons in a more complex manner compared to the effects seen in the periphery. The more complex effects seen for responses to tones in quiet and in noisy background are likely to result from a complex interplay between altered afferent input in the cochlea and central circuitry. In addition, the ability of MOC efferents in suppressing the normal and abnormal spontaneous activity in the midbrain also could have implications for the role of the descending system in the pathophysiology and treatment of tinnitus.

During vestibular schwannoma surgery a large proportion of patients will lose their hearing. While there have been several papers investigating the mechanism behind this loss of auditory function, the exact pathophysiological mechanisms remain relatively elusive. The present study aimed to document the patterns of electrophysiological auditory responses during retrosigmoid vestibular schwannoma surgery. In particular, we aimed to determine whether the site of auditory impairment in individual cases was predominantly cochlea or neural. Auditory function was monitored intraoperatively in two patients who underwent unilateral vestibular schwannoma surgery via the retrosigmoid approach at St George’s Hospital in Christchurch, and Dunedin Public Hospital. A combination of electrocochleography and direct eighth nerve monitoring techniques were used to monitor the auditory evoked potentials from the cochlea and cochlear nerve during the course of the surgery. Auditory brainstem response recordings were obtained from the second participant due to the technical difficulties in the primary electrophysiological techniques. Technical difficulties faced during the surgical procedure prevented the recording of both electrocochleography and direct eighth nerve monitoring potentials from each of the participants. As a consequence of this, we were unable to draw any conclusions about the site of iatrogenic injury in each surgery. Despite the insufficient recordings of auditory function, the technical and practical knowledge acquired during the course of this pilot study has established a foundation upon which the continuing research may build.

Grâce à la miniaturisation de la technologie ainsi qu'a l'augmentation constante des capacités de calcul numérique, les méthodes objectives et les appareils de mesures de la physiologie auditive évoluent. C'est dans l'optique de créer de nouveaux outils diagnostics que la société Echodia a été créée en 2009. Celle-ci finance aujourd'hui mes recherches sous convention CIFRE.Les présents travaux proposent, dans une première partie, de présenter comment deux méthodes de mesures non invasives ont été mises en oeuvre pour être applicables au diagnostic de l'hydrops cochléaire. Les méthodes sont basées sur le fait que les réponses des cellules ciliées de la cochlée à des stimuli sonores dépendent de la position au repos de leur touffe de stéréocils. Or, l'hydrops cochléaire, l'une des principales caractéristiques de la maladie de Menière, est susceptible de venir perturber cet environnement. Une variation chimique ou mécanique de celui-ci peut ainsi être mise en évidence par différentes méthodes d'exploration objectives. La première est basée sur un enregistrement électrophysiologique. En étudiant le Potentiel de sommation (SP) de l'ÉlectroCochléoGraphie (ECochG), nous allons recueillir une image du tour basal de la cochlée. La deuxième méthode est basée sur un enregistrement acoustique dans le méat acoustique externe. En monitorant le déphasage des Produits de distorsion desoto-émissions acoustiques (DPOAE), nous allons enregistrer les réponses du tour apical de la cochlée.La deuxième partie est consacrée à une étude au cours de laquelle nous avons enregistré de manière concomitante le SP (basal) ainsi que le DPOAE (apical) chez 73 patients souffrant de vertiges de Menière, à proximité d'une attaque (n = 40) ou entre les attaques, sans symptômes cliniques (n = 33). Dans le cas des DPOAE, c'est la phase du produit de distorsion (PDA) à 2*f1-f2 qui a été étudiée en réponse à des sons stimulants de fréquence f1 = 1 kHz et f2 = 1,2 kHz. La puissance des deux fondamentaux a été fixée entre 70 et 75dB SPL en fonction du niveau du DPOAE. Le rapport entre SP et le Potentiel d’action global (AP) a, quant à lui, été mesuré de manière extra-tympanique en réponse à des clics de 95dB nHL. Ces deux mesures ont été effectuées plusieurs fois pendant un test de posture afin d'évaluer leur stabilité.Les limites normales de déphasage du DPOAE en réponse à la posture [-18 °, +38 °] ont été dépassées chez 75% des patients étant venus consulter à proximité d'une crise. Sur ces mêmes sujets, l'étude du ratio entre SP et AP a dépassé la valeur normale (<0,40) dans 60% des cas. De plus, chez les patients à proximité d'une crise de vertige, les deux types de mesures révèlent des fluctuations entre deux répétitions. Ces écarts mettent en évidence combien l'hydrops entrave le bon fonctionnement de la mécanique cochléaire. Le fait de constater des variations sur des échelles de temps aussi courtes pourrait expliquer la sensibilité imparfaite des tests diagnostics. En effet, les protocoles de mesure du SP ou des DPOAE nécessitent un moyennage des acquisitions qui, par définition, a tendance à niveler les fluctuations transitoires
Thanks to technology miniaturization as well as digital computing abilities steadily increasing, objective measurement methods and their related devices evolve. Echodia company was created in 2009 with the goal to create new diagnostic tools. The company currently supports my research work through a CIFRE convention.The first part of this thesis presents two non-invasive measurement methods that have been implemented to the diagnosis of cochlear hydrops. The methods are based on the responses of cochlear hair cells to sound stimuli, depending themselves on the resting position of their stereocilia bundles. Cochlear hydrops, a hallmark of Meniere's disease, is likely to disturb this environment. A chemical or mechanical variation of this environment may be observed by various objective exploration methods. The first method is based on an electrophysiological recording. By studying the Summating Potential (SP) of the Electrocochleography (ECOG) we will register activity in the basal part of the cochlea. The second method is based on a sound recording in the external acoustic meatus. By monitoring the phase shifts of Distortion-Product OtoAcoustic Emissions (DPOAE), we will record the apical responses of the cochlea.The second part of this thesis focuses on a study in which we recorded concomitantly the SP (basal) and the DPOAE (apical) in 73 patients with Menière's disease, close to an attack (n = 40) or between attacks without clinical symptoms (n = 33). In the case of DPOAE, the phase at 2*f1-f2 has been studied in response to pure sinusoidal sounds at frequency f1 = 1 kHz and f2 = 1,2 kHz. The power of the two primary was set between 70 and 75dB SPL based on the level of the DPOAE. The SP to Action Potential (AP) ratio has been measured by extra-tympanic electrode in response to 95dB nHL clicks. These two measurements were performed several times during a postural test to evaluate their stability.The normal limit of the phase shift of the DPOAE during a postural test [-18 °, +38 °] was exceeded in 75% of patients near an attack. On these subjects, the study of the SP/AP ratio exceeded the normal value (<0.40) in 60% of cases. In addition, the two types of measurements made on patients near a vertigo attack reveal fluctuations between reiteration. These differences highlight how hydrops hinders the proper functioning of the cochlear mechanics. This short time scales fluctuations might explain the imperfect diagnostic sensitivity of SP and DPOAE tests, as averaging procedures would tend to level out transient fluctuations characteristic of hydrops

[Truncated abstract] The present study investigated whether any of the characteristics of the compound action potential (CAP) waveform or the spectrum of the neural noise (SNN) recorded from the cochlea, could be used to examine abnormal spike generation in the type I primary afferent neurones, possibly due to pathologies leading to abnormal hearing such as tinnitus or tone decay. It was initially hypothesised that the CAP waveform and SNN contained components produced by the local action currents generated at the peripheral ends of the type I primary afferent neurones, and that changes in these local action currents occurred due to changes in the membrane potential of these neurones. It was further hypothesised that the lateral olivo-cochlear system (LOCS) efferent neurones regulate the membrane potential of the primary afferent dendrites to maintain normal action potential generation, where instability in the membrane potential might lead to abnormal primary afferent firing, and possibly one form of tinnitus. We had hoped that the activity of the LOCS efferent neurones could be observed through secondary changes in the CAP waveform and SNN, resulting from changes in the membrane potential of the primary afferent neurones. The origins of the neural activity generating the CAP waveform and SNN peaks, and the effects of the LOCS on the CAP and SNN were experimentally investigated in guinea pigs using lesions in the auditory system, transient ischemia and asphyxia, focal and systemic temperature changes, and pharmacological manipulations of different regions along the auditory pathway. ... Therefore, the CAP and SNN are altered by changes in the propagation of the action potential along the primary afferent neurones, by changes in the morphology of the tissues surrounding the cochlear nerve, and by changes in the time course of the action currents. If the CAP waveform is not altered, the amplitude of the 1kHz speak in the spontaneous SNN can be used as an objective measure of the spontaneous firing rate of the cochlear neurones. However, because the SNN contains a complex mixture of neural activity from all cochlear neurones, and the amplitude of the spontaneous SNN is variable, it would be difficult to use the spontaneous SNN alone as a differential diagnostic test of cochlear nerve pathologies. To record extratympanic electrocochleography (ET ECochG) from humans, a custom-designed, inexpensive, low-noise, optically isolated biological amplifier was built. Furthermore, a custom-designed extratympanic active electrode and ear canal indifferent electrode were designed, which increased the signal-to-noise ratio of the ECochG recording by a factor of 2, decreasing the overall recording time by 75%. The human and guinea pig CAP waveforms recorded in the present study appeared similar, suggesting that the origins of the human and guinea pig CAP waveforms were the same, and that experimental manipulations of the guinea pig CAP waveform can be used to diagnose the cause of abnormal human ECochG waveforms in cases of cochlear nerve pathologies.

Ménière’s disease (MD) is an inner ear condition characterised by progressive hearing loss, tinnitus, aural fullness, and vertigo. Migraine is a common, chronic neurovascular disorder characterised by attacks of severe headaches, autonomic nervous system dysfunction, and, in some patients, visual disturbances. Patients with certain subclasses of migraine may also present with symptoms typically experienced by MD sufferers, such as vertigo, hearing loss, and tinnitus. Currently most MD cases are diagnosed through subjective criteria such as the guidelines provided by the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing Equilibrium (AAO-HNS CHE) and the Gibson score. Migraine is diagnosed subjectively according to the International Headache Society (IHS). The purpose of this study was to investigate whether tone burst Electrocochleography (ECochG) measures, which have been found to be effective in assisting with the diagnosis of MD, may be sensitive in differentiating between suspected MD patients with and without a history of migraine. A database of 395 patients, whose medical files included ECochG records, was analysed. The ECochG data and other patient characteristics were compared between three groups, including patients who had a history of migraine and attacks of vertigo (“Migraine”), patients who had no history of migraine but reported having had headaches and attacks of vertigo (“No migraine-with headache”), and patients who reported having had attacks of vertigo but neither a history of migraine nor headaches (“No migraine-without headache”). The “Migraine” group was found to have a significantly higher proportion of “negative” ECochG cases compared to the other two groups. The “Migraine” group also had the lowest occurrence of hearing loss and lowest mean Gibson scores amongst the three groups. These findings suggest that some patients who are subjectively diagnosed with MD may have vestibular migraine instead of MD. It is, therefore, concluded that utilisation of physiological test such as ECochG may improve the differential diagnosis of MD and vestibular migraine.

Disabling hearing loss is a problem around the world, with the World Health Organization estimating that 466 million people worldwide have disabling loss, and that this number is expected to increase to over 900 million people by 2050. There are different types of hearing loss, but sensorineural hearing loss (SNHL) is the most common and results from damage to the inner ear. The audiogram is the most common test used to diagnose hearing loss, but it is limited in that it can only identify a shift in hearing sensitivity (thresholds), i.e., it cannot identify the cochlear location causing SNHL. The electrocochleogram (ECochG) is an evoked response consisting of several summed responses of electrical potentials from within the inner ear. Several components represent activity from different places in the inner ear: the compound action potential (CAP) is the summed onset response of auditory nerve fibers, the cochlear microphonic (CM) is the AC response of the hair cells (primarily outer hair cells), and the summating potential (SP) is the DC hair cell response (primarily inner hair cells). Most ECochG responses in humans are collected non-invasively (e.g., from the ear canal or ear drum), whereas most ECochG responses in animal models are collected invasively (e.g., from the cochlear round window).

In this project, we aimed to bridge this gap by recording non-invasive ECochG responses from awake chinchillas. We first started by calculating standard ECochG metrics from existing data across different forms of SNHL. Next, we tested the feasibility of recording non-invasive ECochG responses from the ear canals of awake chinchillas. Finally, we defined and calculated additional metrics from ECochG responses to further help in identifying location(s) of SNHL. The ability demonstrated here to record non-invasive ECochG responses from awake animals increases the translational applicability of pre-clinical SNHL animal models by permitting detailed cochlear assessments at multiple time points post exposure. Detailed ECochG measures can advance hearing science and audiology by helping to identify the location of damage causing the hearing loss, which can ultimately allow for more individualized treatment.

THE DEPARTMENT OF SPEECH PATHOLOGY AND AUDIOLOGY. FACULTY OF ARTS, UNIVERSITY OF THE WITWATERSRAND, JOHANNESBURG In partial fulfillment of the requirements for the degree of Master of Arts by coursework in Audiology June 1999
High stimulus repetition rates have been proposed as a solution to the poor sensitivity and specificity of the standard electrocochleogram. The use of this approach has been confounded, however, by conflicting literature reports on the effects of high stimulus repetition rates on normal subjects. This study aimed to confirm the effects of high stimulus repetition rates on normal hearing subjects as a precursor to clinical high stimulus repetition rate electrocochleography trials. Electrocochleogram tracings were recorded binaurally from 51 normal hearing subjects at 7.1 cps, 51.1 cps, 101.1 cps and 151.1 cps and the summating potential and action potential latencies and amplitudes, summating potential/action potential amplitude ratios and waveform widths were recorded. Statistical analyses showed that increasing the stimulus repetition rate caused statistically (p