Graeme Clark Collection
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ItemThe multi-channel cochlear implant and the relief of severe-to-profound deafness.(Informa UK Limited, 2012-05)This personal reflection outlines the discoveries at the University of Melbourne leading to the multi-channel cochlear implant, and its development industrially by Cochlear Limited. My earlier experimental electrophysiological research demonstrated temporal coding occurred for only low frequencies, i.e. below 200-500 pulses/second. I was able to confirm these findings perceptually in behaviourally conditioned animals. In addition, these studies showed that temporal discrimination occurred across spatial coding channels. These experimental results correlated with the later conscious experience for electrical stimulation in my implant patients. In addition, the mid-to-high frequencies were coded in part by place of stimulation using bipolar and monopolar stimulation to restrict current spread. Furthermore, place of stimulation had the qualities of sharpness and dullness, and was also experienced as vowels. Owing to the limitation in coding speech with a physiological model due to the overlap of electrical current leading to unpredictable variations in loudness, a speech coding strategy that extracted the most important speech features for transmission through an electro-neural 'bottle-neck' to the brain was explored. Our inaugural strategy, discovered in 1978, extracted the second formant for place of stimulation, voicing for rate of stimulation, and sound pressure for current level. This was the first coding strategy to provide open-set speech understanding, as shown by standard audiological tests, and it became the first clinically successful interface between the world and human consciousness. This strategy was improved with place coding for the third formant or high-frequency spectrum, and then the spectral maxima. In 1989, I operated on our first patient to receive a bilateral implant, and in 1990, the first with a bimodal processor. The psychophysics and speech perception for these showed that the stimuli from each side could be fused into a single image, and localized according to differences in intensity and time of arrival of the stimuli. There were significant improvements for speech perception in noise. In 1985, I implanted our first children with the multi-channel prosthesis and found that speech understanding and spoken language were greatly improved the younger the child at surgery, and especially when younger than 12 months. Speech understanding was strongly related to the development of place coding. In 1990, the US Food and Drug Administration approved the implant for deaf children, the first by any world health regulatory body making it the first major advance in helping deaf children to communicate.
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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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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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ItemDelayed neurotrophin treatment supports auditory neuron survival in deaf guinea pigs [Abstract]( nd)The cochlear implant provides auditory cues to patients with a severe profound hearing loss by direct electrical stimulation of the auditory nerve. As such, the total number and integrity of the surviving auditory neuron population may govern the benefits that patients can derive from the implants. Therefore, the rescue of auditory neurons from degeneration following the loss of hair cells is of great therapeutic significance. Neurotrophic factors are known to be important for the development and maintenance of the auditory system I, and have also been rep6rted to act as survival factors for auditory neurons in animal models of deafness. However, while studies have demonstrated that the application of neurotrophins into the inner ear shortly following deafening can prevent auditory neuron degeneration2,3, much less is known about the survival effects of delayed neurotrophin treatment, which is a clinically more realistic model. This study therefore examined the effects of delayed neurotrophin treatment on auditory neuron survival following deafening. Specifically, we aimed to determine if any or all of the neurotrophins -BDNF, NT -3, NT-4/5 and NGF -could rescue neurons from degeneration after a period of two weeks of deafuess. Normal hearing guinea pigs were bilaterally deafened J using a combination of the aminoglycoside kanamycin and the loop diuretic frusemide. Two weeks later the left cochleae were implanted with a cannula attached to a mini-osmotic pump, which delivered 10Ilg of neurotrophin over a period of 28 days. The right cochleae acted as deafened and untreated controls. Despite the delayed treatments, each of the four neurotrophins prevented the degeneration of auditory neurons that is normally seen following loss of hair cells. When compared to normal hearing animals, the neuronal survival rates of deafened, neurotrophin-treated animals ranged between 79 87%; in contrast, deafened, untreated controls displayed only 52% neuronal survival. Current work is also investigating the expression patterns of the neurotrophin Trk receptors in relation to these findings, and these results will also be discussed. The results of this study provide further support to the theory that neurotrophic factors may be able to be used as therapeutic agents for the benefit of the hearing impaired community.