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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ItemPromoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodes(WILEY, 2009-10)Release of neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF) from hair cells in the cochlea is essential for the survival of spiral ganglion neurons (SGNs). Loss of hair cells associated with a sensorineural hearing loss therefore results in degeneration of SGNs, potentially reducing the performance of a cochlear implant. Exogenous replacement of either or both neurotrophins protects SGNs from degeneration after deafness. We previously incorporated NT3 into the conducting polymer polypyrrole (Ppy) synthesized with para-toluene sulfonate (pTS) to investigate whether Ppy/pTS/NT3-coated cochlear implant electrodes could provide both neurotrophic support and electrical stimulation for SGNs. Enhanced and controlled release of NT3 was achieved when Ppy/pTS/NT3-coated electrodes were subjected to electrical stimulation. Here we describe the release dynamics and biological properties of Ppy/pTS with incorporated BDNF. Release studies demonstrated slow passive diffusion of BDNF from Ppy/pTS/BDNF, with electrical stimulation significantly enhancing BDNF release over 7 days. A 3-day SGN explant assay found that neurite outgrowth from explants was 12.3-fold greater when polymers contained BDNF (p < 0.001), although electrical stimulation did not increase neurite outgrowth further. The versatility of Ppy to store and release neurotrophins, conduct electrical charge, and act as a substrate for nerve-electrode interactions is discussed for specialized applications such as cochlear implants.
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ItemConducting polymers, dual neurotrophins and pulsed electrical stimulation - Dramatic effects on neurite outgrowth(ELSEVIER SCIENCE BV, 2010-01-25)In this study the synergistic effect of delivering two neurotrophins simultaneously to encourage neuron survival and neurite elongation was explored. Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) were incorporated into polypyrrole (PPy) during electrosynthesis and the amounts incorporated and released were determined using iodine-125 ((125)I) radio-labelled neurotrophins. Neurite outgrowth from cochlear neural explants grown on the conducting polymer was equivalent to that on tissue culture plastic but significantly improved with the incorporation of NT-3 and BDNF. Neurite outgrowth from explants grown on polymers containing both NT-3 and BDNF showed significant improvement over PPy doped only with NT-3, due to the synergistic effect of both neurotrophins. Neurite outgrowth was significantly improved when the polymer containing both neurotrophins was electrically stimulated. It is envisaged that when applied to the cochlear implant, these conducting and novel polymer films will provide a biocompatible substrate for storage and release of neurotrophins to help protect auditory neurons from degradation after sensorineural hearing loss and encourage neurite outgrowth towards the electrodes.
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ItemNo Preview AvailablePolypyrrole-coated electrodes for the delivery of charge and neurotrophins to cochlear neurons(ELSEVIER SCI LTD, 2009-05)Sensorineural hearing loss is associated with gradual degeneration of spiral ganglion neurons (SGNs), compromising hearing outcomes with cochlear implant use. Combination of neurotrophin delivery to the cochlea and electrical stimulation from a cochlear implant protects SGNs, prompting research into neurotrophin-eluting polymer electrode coatings. The electrically conducting polypyrrole/para-toluene sulfonate containing neurotrophin-3 (Ppy/pTS/NT3) was applied to 1.7 mm2 cochlear implant electrodes. Ppy/pTS/NT3-coated electrode arrays stored 2 ng NT3 and released 0.1 ng/day with electrical stimulation. Guinea pigs were implanted with Ppy/pTS or Ppy/pTS/NT3 electrode arrays two weeks after deafening via aminoglycosides. The electrodes of a subgroup of these guinea pigs were electrically stimulated for 8 h/day for 2 weeks. There was a loss of SGNs in the implanted cochleae of guinea pigs with Ppy/pTS-coated electrodes indicative of electrode insertion damage. However, guinea pigs implanted with electrically stimulated Ppy/pTS/NT3-coated electrodes had lower electrically-evoked auditory brainstem response thresholds and greater SGN densities in implanted cochleae compared to non-implanted cochleae and compared to animals implanted with Ppy/pTS-coated electrodes (p<0.05). Ppy/pTS/NT3 did not exacerbate fibrous tissue formation and did not affect electrode impedance. Drug-eluting conducting polymer coatings on cochlear implant electrodes present a clinically viable method to promote preservation of SGNs without adversely affecting the function of the cochlear implant.
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ItemThe effect of polypyrrole with incorporated neurotrophin-3 on the promotion of neurite outgrowth from auditory neurons(ELSEVIER SCI LTD, 2007-01)This research aims to improve the nerve-electrode interface of the cochlear implant using polymer technology to encourage neuron survival, elongation and adhesion to the electrodes. Polypyrrole (Ppy) doped with p-toluene sulphonate (pTS) is an electroactive polymer into which neurotrophin-3 (NT3) can be incorporated. Ppy/pTS+/-NT3 was synthesised over gold electrodes and used as a surface for auditory neuron explant culture. Neurite outgrowth from explants grown on Ppy/pTS was equivalent to tissue culture plastic but improved with the incorporation of NT3 (Ppy/pTS/NT3). Electrical stimulation of Ppy/pTS/NT3 with a biphasic current pulse, as used in cochlear implants, significantly improved neurite outgrowth from explants. Using (125)I-NT3, it was shown that low levels of NT3 passively diffused from Ppy/pTS/NT3 during normal incubation and that electrical stimulation enhanced the release of biologically active NT3 in quantities adequate for neuron survival. Furthermore, Ppy/pTS/NT3 and its constituents were not toxic to auditory neurons and the Ppy/pTS/NT3 coating on gold electrodes did not alter impedance. If applied to the cochlear implant, Ppy/pTS/NT3 will provide a biocompatible, low-impedance substrate for storage and release of NT3 to help protect auditory neurons from degradation after sensorineural hearing loss and encourage neurite outgrowth towards the electrodes.
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ItemSpeech perception as a function of electrical stimulation rate: using the nucleus 24 cochlear implant system( 2000)Objective: To investigate the effect of varying electrical stimulation rate on speech comprehension by cochlear implant users, while keeping the number of stimulated channels constant. Design: Three average rates of electrical stimulation,250, 807, and 1615 pulses per second per channel (pps/ch), were compared using a speech processing strategy that employed an electrode selection technique similar to that used in the Spectral Maxima Sound Processor strategy (McDermott, McKay,& Vandali, 1992; McDermott & Vandali, Reference Note 1; McKay, McDermott, Vandali, & Clark, 1991)and the Spectral Peak strategy (Skinner et al., 1994;Whitford et al., 1995). Speech perception tests with five users of the Nucleus 24 cochlear implant system were conducted over a 21-wk period. Subjects were given take-home experience with each rate condition. A repeated ABC evaluation protocol with alternating order was employed so as to account for learning effects and to minimize order effects. Perception of open-set monosyllabic words in quiet and open-set sentences at signal to noise ratios ranging from +20 to 0 dB, depending on the subject’s ability, were tested. A comparative performance questionnaire was also administered. Results: No statistical differences in group performance between the 250 and 807 pps/ch rates were observed in any of the speech perception tests. However, significantly poorer group performance was observed for the 1615 pps/ch rate for some tests due predominantly to the results of one subject. Analysis of individual scores showed considerable variation across subjects. For some subjects, one or more of the three rate conditions evaluated provided benefits on some speech perception tasks. The results of the comparative performance questionnaire indicated a preference for the 250 and 807pps/ch rates over the 1615 pps/ch rate for most listening situations. Conclusions: For the speech processing strategy, implant system, and subjects evaluated in this study, the group results indicated that the use of electrical stimulation rates higher than 250 pps/ch (up to 1615 pps/ch) generally provided no significant improvement to speech comprehension. However, individual results indicated that perceptual.
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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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ItemChronic electrical stimulation of the auditory nerve using non-charge-balanced stimuli( 1999)This study was designed to evaluate the pathophysiological response of the cochlea following long-term intracochlear electrical stimulation using a poorly charge-balanced stimulus regime, leading to direct current (DC) levels >0.1 µA. Four normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods up to 2200 h. Stimuli consisted of 50 µs monophasic current pulses presented at 2000 pulses per second (pps) per channel, and resulted in DC levels of 0.4-2.8 µA. Both acoustic and electrical (EABR) evoked potentials were periodically recorded during the stimulation program. Frequency-specific stimuli indicated that an extensive and widespread hearing loss occurred over the 4-24 KHz region in all stimulated cochleae, although the 2 KHz region exhibited thresholds close to normal in some animals, despite long-term implantation and chronic stimulation. Longitudinal EABRs showed a statistically significant increase in threshold for three of the four animals. Histopathological evaluation of the cochleae revealed a highly significant reduction in ganglion cell density in stimulated cochleae compared with their controls. Spiral ganglion cell loss was significantly correlated with the degree of inflammation, duration of electrical stimulation, and the level of DC. In conclusion, the present study highlights the potential for neural damage following stimulation using poorly charge-balanced stimuli.
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ItemIntracellular responses of the rat anteroventral cochlear nucleus to intracochlear electrical stimulation( 1998)Unavailable due to copyright.