Graeme Clark Collection

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    Midbrain responses to micro-stimulation of the cochlea using high density thin-film arrays
    Allitt, BJ ; Morgan, SJ ; Bell, S ; Nayagam, DAX ; Arhatari, B ; Clark, GM ; Paolini, AG (ELSEVIER SCIENCE BV, 2012-05-01)
    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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    Promoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodes
    Evans, AJ ; Thompson, BC ; Wallace, GG ; Millard, R ; O'Leary, SJ ; Clark, GM ; Shepherd, RK ; Richardson, RT (WILEY, 2009-10-01)
    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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    Polypyrrole-coated electrodes for the delivery of charge and neurotrophins to cochlear neurons
    Richardson, 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, 2009-05-01)
    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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    A multiple-electrode cochlear implant
    Clark, Graeme M. ; Tong, Y. C. ; Bailey, Q. R. ; Black, R. C. ; Martin, L. F. ; Millar, J. B. ; O'Loughlin B. J. ; Patrick, J. F. ; Pyman, B. C. ( 1978)
    Interest in artificially stimulating the auditory nerve electrically for sensori-neural deafness was first sparked off by Volta in the 18th century. Count Volta, who was the first to develop the electric battery, connected up a number of his batteries to two metal rods which he inserted into his ears. Having placed the rods in his ears he pressed the switch and received "une secousse dans la tete" and perceived a noise like "the boiling of thick soup".
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    Hearing restoration with the multichannel auditory brainstem implant
    Briggs, 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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    Speech perception as a function of electrical stimulation rate: using the nucleus 24 cochlear implant system
    Vandali, Andrew E. ; Whitford, Lesley A. ; Plant, Kerrie L. ; Clark, Graeme M. ( 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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    Chronic electrical stimulation of the auditory nerve at high stimulus rates: a physiological and histopathological study
    XU, JIN ; Shepherd, Robert K. ; Millard, Rodney E. ; Clark, Graeme M. ( 1997)
    A major factor associated with recent improvements in the clinical performance of cochlear implant patients has been the development of speech-processing strategies based on high stimulation rates. While these processing strategies show clear clinical advantage, we know little of their long-term safety implications. The present study was designed to evaluate the physiological and histopathological effects of long-term intracochlear electrical stimulation using these high rates. Thirteen normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods of up to 2100 h using either two pairs of bipolar or three monopolar stimulating electrodes. Stimuli consisted of short duration (25-50 µs/phase) charge-balanced biphasic current pulses presented at 1000 pulses per second (pps) per channel for monopolar stimulation, and 2000 pps/channel for bipolar stimulation. The electrodes were shorted between current pulses to minimize any residual direct current, and the pulse trains were presented using a 50% duty cycle (500 ms on; 500 ms oft) in order to simulate speech. Both acoustic (ABR) and electrical (EABR) auditory brainstem responses were recorded periodically during the chronic stimulation program, All cochleas showed an increase in the click-evoked ABR threshold following implant surgery; however, recovery to near-normal levels occurred in approximately half of the stimulated cochleas 1 month post-operatively. The use of frequency-specific stimuli indicated that the most extensive hearing loss generally occurred in the high-frequency basal region of the cochlea (12 and 24 kHz) adjacent to the stimulating electrode. However, thresholds at lower frequencies (2, 4 and 8 kHz), appeared at near-normal levels despite long-term electrode implantation and electrical stimulation. Our longitudinal EABR results showed a statistically significant increase in threshold in nearly 40% of the chronically stimulated electrodes evaluated; however, the gradient of the EABR input/output (I/O) function (evoked potential response amplitude versus stimulus current) generally remained quite stable throughout the chronic stimulation period. Histopathological examination of the cochleas showed no statistically significant difference in ganglion cell densities between cochleas using monopolar and bipolar electrode configurations (P = 0.67), and no evidence of cochlear damage caused by high-rate electrical stimulation when compared with control cochleas. Indeed, there was no statistically significant relationship between spiral ganglion cell density and electrical stimulation (P = 0.459), or between the extent of loss of inner (IHC, P = 0.86) or outer (OHC, P=0.30) hair cells and electrical stimulation. Spiral ganglion cell loss was, however, influenced by the degree of inflammation (P=0.016) and electrode insertion trauma. These histopathological findings were consistent with the physiological data. Finally, electrode impedance, measured at completion of the chronic stimulation program, showed close correlation with the degree of tissue response adjacent to the electrode array. These results indicated that chronic intracochlear electrical stimulation, using carefully controlled charge-balanced biphasic current pulses at stimulus rates of up to 2000 pps/channel, does not appear to adversely affect residual auditory nerve elements or the cochlea in general. This study provides an important basis for the safe application of improved speech-processing strategies based on high-rate electrical stimulation.
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    Acoustic and electric forward-masking of the auditory nerve compound action potential: evidence for linearity of electro-mechanical transduction
    McAnally, Ken I. ; Brown, Mel ; Clark, Graeme M. ( 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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    Electrical stimulation of the auditory nerve with a cochlear implant and the temporal coding of sound frequencies: a brief review
    Clark, Graeme M. ( 1997)
    There is considerable evidence that the brain translates (encodes) the frequency of a sound into both place of excitation (place encoding), and the pattern of intervals between action potentials (temporal encoding). Furthermore, temporal encoding is now thought to be due to a temporal as well as spatial pattern of action potentials in a small group of neurons. This pattern needs to be reproduced with a cochlear implant for improved speech processing. Our recent research has also demonstrated that the timing of excitatory postsynaptic potentials seen with intracellular recordings from brain cells, rather than extracellularly recorded action potentials, correlates better with the frequency of sound. These excitatory postsynaptic potentials are likely to be the link between the patterns of action potentials arriving at nerve cells and the biomolecular activity in the cell. This response also needs to be replicated with improved speech processing strategies.
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    Effects of chronic electrical stimulation on spiral ganglion neuron survival and size in deafened kittens
    Araki, Susumu ; Kawano, Atsushi ; Seldon, H. Lee ; Shepherd, Robert K. ; Funasaka, Sotaro ; Clark, Graeme M. ( 1998)
    We have studied spiral ganglion cell (SGC) survival and soma size in neonatally pharmacologically deafened kittens. They were implanted with a four-electrode array in the left cochlea at 100 to 180 or more days of age. Eight animals were chronically stimulated approximately 1000 hours over approximately 60 days with charge-balanced, biphasic current pulses; three were unstimulated controls. Using three-dimensional computer-aided reconstruction of the cochlea, the SGC position and cross-sectional area were stored. SGC position was mapped to the organ of Corti by perpendicular projections, starting from the basal end. The basal region of the cochlea was divided into three 4-mm segments. SGC survival (number per 0.1 mm of the length of the organ of Corti) and soma size for stimulated cochleae were compared statistically with implanted but unstimulated cochleae. There was no evidence of an effect of electrical stimulation on SGC survival under this protocol and with this duration. On the other hand, the cell size on the stimulated side was significantly larger than the control side in the middle segment (4 to 8 mm from the basal end). SGCs undergo a reduction in size after prolonged auditory deprivation; however, these changes may be partially moderated after chronic intracochlear electrical stimulation.