- Graeme Clark Collection
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ItemThe multi-channel cochlear implant and the relief of severe-to-profound deafness.Clark, G (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 arraysAllitt, BJ ; Morgan, SJ ; Bell, S ; Nayagam, DAX ; Arhatari, B ; Clark, GM ; Paolini, AG (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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ItemNo Preview AvailableCan we prevent cochlear implant recipients from developing pneumococcal meningitis?Wei, BPC ; Robins-Browne, RM ; Shepherd, RK ; Clark, GM ; O'Leary, SJ (Oxford University Press (OUP), 2008-01-01)The restoration of hearing to persons with severely or profoundly impaired hearing by means of a cochlear implant is one of the great achievements of bionics applied to medicine. However, pneumococcal meningitis in implant recipients has received high profile public attention as a result of the US Food and Drug Administration's public health notification and recent media attention. Worldwide, 118 of the 60,000 people who received cochlear implants over the past 20 years have acquired meningitis, causing deep concern in the international medical community. This review provides answers to pediatricians, internists, and infectious diseases doctors who have patients with cochlear implants and who have questions about the safety of the cochlear implant from both the clinical and scientific research perspectives. Both clinical and laboratory research support the notion that pneumococcal meningitis is more likely in patients who receive cochlear implantation, and that the surgical insertion technique and the cochlear implant design should be nontraumatic, and that all cochlear implant recipients should be offered vaccination against Streptococcus pneumoniae.
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ItemPromoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodesEvans, AJ ; Thompson, BC ; Wallace, GG ; Millard, R ; O'Leary, SJ ; Clark, GM ; Shepherd, RK ; Richardson, RT (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 neuronsRichardson, RT ; Wise, AK ; Thompson, BC ; Flynn, BO ; Atkinson, PJ ; Fretwell, NJ ; Fallon, JB ; Wallace, GG ; Shepherd, RK ; Clark, GM ; O'Leary, SJ (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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ItemHearing restoration with the multichannel auditory brainstem implantBriggs, R. J. S. ; Kaye, A. H. ; Dowell, R. C. ; Hollow, R. D. ; Clark, Graeme M. ( 1997)Restoration of useful hearing is now possible in patients with bilateral acoustic neuromas by direct electrical stimulation of the cochlear nucleus. Our first experience with the Multichannel Auditory Brainstem Implant is reported. A forty four year old female with bilateral acoustic neuromas and a strong family history of Neurofibromatosis Type II presented with profound bilateral hearing impairment. Translabyrinthine removal of the right tumour was performed with placement of the Nucleus eight electrode Auditory Brainstem Implant. Intraoperative electrically evoked auditory brainstem response monitoring successfully confirmed placement over the cochlear nucleus. Postoperatively, auditory responses were obtained on stimulation of all electrodes with minimal non-auditory sensations. The patient now receives useful auditory sensations using the "SPEAK" speech processing strategy. Auditory brainstem Implantation should be considered for patients with Neurofibromatosis Type II in whom hearing preservation tumour removal is not possible.
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ItemDelayed neurotrophin treatment supports auditory neuron survival in deaf guinea pigs [Abstract]Gillespie, Lisa. N. ; Clark, Graeme M. ; Marzella, Phillip L. ( 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.
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ItemStiffness properties for nucleus standard straight and contour electrode arraysKha, H. N. ; Chen, B. K. ; Clark, Graeme M. ; Jones, R. ( 2004)Trauma and damage during insertion of electrode arrays into the human cochlea are strongly related to the stiffness of the array. The stiffness properties of electrode arrays, which were determined by three-point flexural bending and buckling tests, are reported in this paper. To date there has been limited publication on mechanical properties of these electrode arrays. Previous studies mainly focused on characterizing the stiffness of the tip of the Nucleus straight array with little emphasis on characterizing the stiffness of its whole length. In this study, stiffnesses of the Nucleus straight and contour electrode arrays have been determined along their length. Young’s modulus of elasticity of the Nucleus straight array has been found to increase from the tip (182 MPa) to the rear end (491 MPa), whereas the stiffness of the contour array is greatest near the tip (480 MPa) and is fairly uniform in the middle and rear sections of the electrode array (380-400 MPa). Buckling experiments have shown that the contour array has much higher critical buckling load (about four times) than the Nucleus straight array. The results from three-point flexural bending and buckling experiments provide significant data for the development of electrode arrays, from which new array designs with improved flexibility can be developed. The results of stiffness properties are also important input for use in finite element models to predict the trajectories during insertion and to help evaluate the effects of different electrode array designs on damage sustained during insertion.
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ItemBionic ears: their development and future advances using neurotrophins and inherently conducting polymersClark, Graeme M. ; Wallace, Gordon ( 2004)The development of the multiple-channel bionic ear for hearing and speech understanding in profoundly deaf people is the result of integrating biological and physical sciences with engineering. It is the first clinically successful restoration of sensory and brain function, and brings electronic technology into a direct functional relationship with human consciousness. It presently transmits essential place and coarse temporal information for the coding of frequency, but the fine temporal and place excitation of groups of nerve fibres is inadequate for high-fidelity sound. This is required for adequate musical appreciation and hearing in noise. Research has demonstrated that nerve growth factors preserve the peripheral processes of the auditory nerves so that an electrode array placed close to these fibres could produce this fine temporal and spatial coding. The nerve growth factors can be incorporated into inherently conducting polymers that are part of the array so the peripheral processes can be preserved at the same time as they arc electrically stimulated.
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ItemCochlear implantsClark, Graeme M. (Springer, 2003)Over the past two decades there has been remarkable progress in the clinical treatment of profound hearing loss for individuals unable to derive significant benefit from hearing aids. Now many individuals who were unable to communicate effectively prior to receiving a cochlear implant are able to do so, even over the telephone without any supplementary visual cues from lip reading. The earliest cochlear implant devices used only a single active channel for transmitting acoustic information to the auditory system and were not very effective in providing the sort of spectrotemporal information required for spoken communication. This situation began to change about 20 years ago upon introduction of implant devices with several active stimulation sites. The addition of these extra channels of information has revolutionized the treatment of the profoundly hearing impaired. Many individuals with such implants are capable of nearly normal spoken communication, whereas 20 years ago the prognosis for such persons would have been extremely bleak. (From Introduction)