Graeme Clark Collection
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ItemMidbrain responses to micro-stimulation of the cochlea using high density thin-film arrays(ELSEVIER SCIENCE BV, 2012-05)A broader activation of auditory nerve fibres than normal using a cochlear implant contributes to poor frequency discrimination. As cochlear implants also deliver a restricted dynamic range, this hinders the ability to segregate sound sources. Better frequency coding and control over amplitude may be achieved by limiting current spread during electrical stimulation of the cochlea and positioning electrodes closer to the modiolus. Thin-film high density microelectrode arrays and conventional platinum ring electrode arrays were used to stimulate the cochlea of urethane-anaesthetized rats and responses compared. Neurophysiological recordings were taken at 197 multi-unit clusters in the central nucleus of the inferior colliculus (CIC), a site that receives direct monaural innervation from the cochlear nucleus. CIC responses to both the platinum ring and high density electrodes were recorded and differences in activity to changes in stimulation intensity, thresholds and frequency coding of neural activation were examined. The high density electrode array elicited less CIC activity at nonspecific frequency regions than the platinum ring electrode array. The high density electrode array produced significantly lower thresholds and larger dynamic ranges than the platinum ring electrode array when positioned close to the modiolus. These results suggest that a higher density of stimulation sites on electrodes that effectively 'aim' current, combined with placement closer to the modiolus would permit finer control over charge delivery. This may equate to improved frequency specific perception and control over amplitude when using future cochlear implant devices.
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ItemA single dose of neurotrophin-3 to the cochlea surrounds spiral ganglion neurons and provides trophic support( 2005)Unavailable due to copyright.
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ItemDelivery of neurotrophin-3 to the cochlea using alginate beads( 2005)Objective: The aim of this study was to design a novel cochlear neurotrophin (NT) delivery system for the rescue of auditory neurons after ototoxicity-induced deafening. Background: NT-3 is a trophic growth factor that promotes the survival of the auditory nerve and may have a potential therapeutical role in slowing neuron loss in progressive deafness, especially as an adjunct to the current cochlear implant. Beads made from alginate are biodegradable, slow release substances that can he placed at the round window or inside the cochlea. This study investigates the loading properties, release kinetics, and implantation potential of alginate beads loaded with NT-3. Methods: Alginate beads were prepared using an ionic gelation technique and postloaded with NT-3. Release of NT-3 was measured using enzyme-linked immunosorbent assay over 5 days. Alginate beads were implanted into deafened guinea pigs for 28 days, after which surviva1 of auditory neurons was assessed. Results: Enzyme-linked immunosorbent assay studies demonstrated a 98%: to 99% loading of NT-3 with a slow, partial release over 5 days in Ringers solution. Furthermore, the addition of heparin to the delivery system modulated NT-3 release to a steadier pattern. Implantation of alginate-heparin beads in guinea pig cochleae produced minimal local tissue reaction NT-3 loaded beads implanted as both the round window and within the scala tympani of the basal turn provided auditory neurons significant protection from degradation and apoptosis compared with unloaded beads or untreated cochleae. Conclusions: This study demonstrates alginate beads to be a safe, biodegradable and effective delivery system for NT-3 to the cochlea.
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ItemTracing neurotrophin-3 diffusion and uptake in the guinea pig cochlea( 2004)Unavailable due to copyright.
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ItemAcoustic and electric forward-masking of the auditory nerve compound action potential: evidence for linearity of electro-mechanical transduction( 1997)We investigated electro-mechanical transduction within the cochlea by comparing masking of the auditory nerve compound action potential (CAP) by acoustical and electrical maskers. Forward-masking of the CAP reflects the response to the masker of the cochlear location tuned to the probe. Electrical stimulation was delivered through bipolar stimulating electrodes within the basal turn of the scala tympani. The growth of masking of high-frequency probes which excite cochlear locations close to the stimulating electrodes was similar for both acoustic and electrical maskers, suggesting a linear transduction of electrical energy to mechanical energy. Exposure to intense acoustic stimulation caused an equal loss of sensitivity to acoustic and electrical maskers. Masking of lower-frequency probes by electrical maskers increased rapidly with masker current, suggesting the direct electrical stimulation of neural elements. This masking was reduced by the administration of strychnine suggesting a contribution by the efferents towards masking of these low-frequency probes.
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ItemGrowth factors, auditory neurones and cochlear implants: a review( 1999)The total number and the integrity of the auditory neurones available for stimulation govern the benefits that patients can derive from cochlear implants. Although electrical stimulation of the cochlea has been reported to promote auditory neuronal survival, this trophic effect is insufficient to regenerate de novo fibres. Hence, any agent that can maximize the number of, or regenerate functional auditory neurones would be of great benefit. Several studies have identified various growth factors crucial to the normal development of auditory neurones. In addition, in vitro studies have demonstrated that several growth factors are important for the maintenance, rescue and repair of adult auditory neurones. In vivo studies confirm the in vitro findings, reporting that specific growth factors are able to support auditory neuronal survival following injury or trauma, and in lower species growth factors have been associated with regenerating auditory neurones. In addition to their trophic actions, several growth factors have also been reported to affect ion channels thus the electrical response of neuronal fibres. Indeed, growth factors have been reported to enhance neuronal excitation and to improve the efficacy of synaptic transmission. Taken in concert, these effects suggest that exogenous growth factors delivered to the cochlea may improve the transmission of the electrical stimuli from the implanted electrode to the auditory pathway. Further studies are warranted to investigate how the adjunct delivery of growth factors with the cochlear implant may constitute a better treatment for hearing-impaired individuals.
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ItemAssessment of intracochlear ossification by three-dimensional reconstruction of computerised scans( 1995)The aim of the study was to investigate whether the three-dimensional (3-D) images from computed tomography (CT) scans of the ears could adequately define the site and extent of new bone in the cochlea, and how these images compared with those created by magnetic resonance imaging (MRI). The patients whose investigations were used in the study were being assessed for a cochlear implant and were selected on the basis of their history and the appearance of their two-dimensional (2-D) CT scans. Four patients had progressive mixed deafness, a family history of deafness, and stapedectomies. They were considered to be deaf from otosclerosis and needed further assessment because their scans showed either obstructed cochleas from new bone, or demineralized otic capsules to the point that we could not determine whether new bone was present or not. The fifth patient was being assessed within 3 months of suffering deafness from meningitis. In one ear he had extensive ossification, and in the other the degree of opacification shown in axial and coronal cuts of the basal turn was inconsistent. Essentially the problem is that at the magnification used in examination of the inner ear, the resolution of 2-D CT scans gives indistinct borders between bone and water. Magnetic resonance imaging has commonly been used in these cases. The study showed that it is now possible to confirm whether or not there is new bone and to demonstrate the site and extent of new bone with both 3-D and MRI images. It is not possible to give a degree of sensitivity and specificity for this observation because of the small group of subjects in the study. It should be worth applying the reconstruction software to scans from helical scanners with a view to assessing whether the resolution of the 3-D images can be improved further.
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ItemComparison of monaural acoustic and electric stimulation: unit types in the cat inferior colliculus( 1995)This study has shown that 1) the ratio of excitatory and inhibitory inputs to units in the central nucleus of the inferior colliculus is altered when one cochlea is neomycin-deafened and/or electrically stimulated; 2) prestimulus threshold shift and lateral inhibition mechanisms can be used to explain these results; and 3) at high current levels a leakage current into the modiolus can evoke unit population responses.
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ItemEnhancement of the radiographic changes in the otic capsule and cochlea due to otosclerosis using three dimensional reconstruction of CT scans( 1995)The otic capsule changes of cochlear otosclerosis are occasionally such that standard high resolution CT scans are not clear enough to determine the significance of edge blurring as a predictive factor for implantation. The use of a software package to produce three dimensional enhancement of the CT images has resolved some of these difficulties in specific cases.
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ItemElectrophysiologic effects following acute intracochlear direct current stimulation of the guinea pig cochlea( 1995)Auditory brain stem responses to both acoustic (auditory brain stem response [ABR]) and electrical (electrically evoked auditory brain stem response [EABR]) stimuli, as well as the frequency-specific compound action potential (CAP), were recorded before and periodically following continuous intracochlear DC stimulation (2, 7, and 12 µA) for 2 hours in normal-hearing guinea pigs, by means of a banded intracochlear electrode array. Click-evoked ABR, frequency-specific CAP, and the EABR input-output function remained generally unchanged following stimulation at 2 µA DC. However, following stimulation at 7and 12 µA, a significant decrement of the amplitude of the click-evoked ABR, frequency-specific CAP, and electrophonic component of the EABR was observed, while there was an increase in the amplitude of the EABR, associated with direct electrical stimulation of the auditory nerve.