Graeme Clark Collection
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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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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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ItemInner ear implants(Dekker, 2004)The cochlear implant is an electronic device that brings useful hearing to severely to profoundly deaf people through multiple-channel electrical stimulation of the auditory nerves in the inner ear. This is required if their inner ears are so badly damaged by injury and disease, or so inadequately developed, that they cannot provide sufficient hearing for communication, even when the sound is amplified with a hearing aid. By stimulating the nerve directly with patterns of electrical pulses, the implant bypasses the normal function of the sense organ of hearing in the inner ear to partially reproduce the coding of sound. It consists of a wearable speech processor that picks up sound with a microphone, analyzes the signal, and then sends it by radio waves to the implanted receiver stimulator, which decodes the message and stimulates the electrode wires inserted into the inner ear.
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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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ItemValidation of a technique for establishing maximum comfortable levels for children using cochlear implants [Abstract]( 2002)The aim of fitting a cochlear implant is to establish electrical stimulation parameters that will provide the wearer with comfortable and useful auditory sensations. One parameter that is fundamental to achieving this aim is the Maximum Comfortable Level (C-level). A C-level is the amount of electrical current that produces a loud, but comfortable sound. C-levels need to be established for all channels that a person will use in their speech processor Map. Determining C-levels can be complicated as the person is required to make a judgment about the loudness of a sound. While most adults and older children have the ability to make such a judgment and provide feedback to the clinician, this is rarely the case for young children. Generally, the only way a clinician will be aware a sound could be too loud for a young child is when they observe the child giving an aversive reaction or an involuntary blink. A current level that produces such a reaction is called the Loudness Discomfort Level (LOL). This study examines the relationship between LDLs and C-levels. Testing was performed with a group of adults, using stimulation rates and stimulation modes that are commonly used by children. The LDL/C-level relationship established in this study provides a procedure for selling C-Levels for young children when only loudness discomfort responses can be obtained.
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ItemAdvances in computational modelling of cochlear implant physiology and perception(IOS Press, 2001)Models of cochlear implant physiology and perception have historically utilized deterministic descriptions of auditory-nerve (AN) responses to electrical stimulation, which ignore stochastic activity present in the response. Physiological models of AN responses have been developed that do incorporate stochastic activity [8][13][14][27][38][39], but the consequences of stochastic activity for the perception of cochlear implant stimulation have not been investigated until recently [3]. Such an investigation is prompted by inaccuracies in predicting cochlear implant perception by deterministic models. For example, studies of single-fiber responses, where only an arbitrary deterministic measure of threshold is recorded, do not accurately predict perceptual threshold versus phase duration (strength-duration) curves for sinusoidal stimulation [24] or for pulsatile stimulation [25][26]. Furthermore, strength-duration curves of cochlear implant users are not well predicted by deterministic Hodgkin Huxley type models [25] [30].However, the complexity of previous stochastic physiological models has made the computation of responses for large numbers of fibers both laborious and time-consuming. Furthermore, the parameters of these models are often not easily matched to the fiber characteristics of the auditory nerve in humans or other mammals. This has prompted us to develop a simpler and more computationally efficient model of electrical stimulation of the auditory nerve [1][2][4] which is capable of direct and rapid prediction of perceptual data[3]
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ItemPhysiological and histopathological effects of chronic monopolar high rate stimulation on the auditory nerve( 2000)Speech processing strategies based on high rate electrical stimulation have been associated with improvements in speech perception among cochlear implant users. The present study was designed to evaluate the electrophysiological and histopathological effects of long-term intracochlear monopolar stimulation at the maximum stimulus rate of the current Nucleus Cochlear implant system (14493 pulses/s) as part of our ongoing investigations of safety issues associated with cochlear implants