Graeme Clark Collection

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    Chronic electrical stimulation of the auditory nerve using non-charge-balanced stimuli
    Shepherd, Robert K. ; Linahan, N. ; Xu, J. ; Clark, Graeme M. ; Araki, S. ( 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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    Chronic electrical stimulation of the auditory nerve at high rates: I. Effect on residual hearing [Abstract]
    Xu, J. ; Shepherd, R. K. ; Clark, Graeme M. ( 1996)
    In addition to direct excitation of auditory nerve fibres, cochlear implant patients with small amounts of residual hearing may receive important additional auditory cues via electrophonic activation of hair cells 1. Before incorporating electrophonic hearing into speech processing strategies, the extent of hair cell survival following cochlear implantation must first be determined. We have recently demonstrated widespread survival of hair cells apical to electrode arrays implanted for periods of up to three years, the present report describes the effects of chronic electrical stimulation on hair cell survival.
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    Chronic electrical stimulation of the auditory nerve at high rates: II. Cochlear pathophysiology [Abstract]
    Shepherd, R. K. ; Xu, J. ; Clark, Graeme M. ( 1996)
    A major factor in the improved performance of cochlear implant patients has been the use of high stimulus rate speech processing strategies. While these strategies show clear clinical advantage, we know little of their long-term safety. Indeed, recent studies have indicated that high stimulus rates at intensities above clinical limits, can result in neural damage as a result of prolonged neuronal hyperactivity. The present study was designed to evaluate the effects of chronic electrical stimulation of the auditory nerve at high rates, using intensities within clinical limits.
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    Spatial representation of the cochlea within the inferior colliculus of neonatally deafened kittens following chronic electrical stimulation of the auditory nerve [Abstract]
    Shepherd, R. K. ; Martin, R. L. ; Brown, M. ; Clark, Graeme M. ( 1995)
    The orderly tonotopic representation of the cochlea is accurately reproduced within the central auditory system of normal hearing animals. Any degradation of this representation as a result of a neonatal hearing loss or chronic electrical stimulation during development could have important implications for the use of multichannel cochlear implants in young children. In the present study we have used 2-deoxyglucose autoradiography (2-00) to examine the topographic representation of the cochlea within the inferior colliculus (IC) of neonatally deafened kittens following periods of chronic intracochlear electrical stimulation.
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    Cochlear histopatholgic characteristics following long-term implantation: safety studies in the young monkey
    Burton, Martin J. ; Shepherd, Robert K. ; Clark, Graeme M. ( 1996)
    Objective: To evaluate the safety of cochlear implantation in children 2 years of age or younger using a non-human primate model.
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    Acute effects of high-rate stimulation on auditory nerve function in guinea pigs
    Tykocinski, M. ; Shepherd, R. K. ; Clark, Graeme M. ( 1995)
    Cochlear implants have been shown to successfully provide profoundly deaf patients with auditory cues for speech discrimination. Furthermore, a number of safety studies using the Melbourne/Cochlear electrode array indicated that chronic electrical stimulation using charge-balanced biphasic current pulses and stimulus rates between 100 and 500 pulses per second (pps) do not result in additional spiral ganglion loss or general cochlear pathology.1-3 However, safe maximum levels for stimulus parameters (stimulus rate, charge per phase, charge density) have not yet been adequately defined.
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    Cochlear pathology following chronic electrical stimulation of the auditory nerve: II Deafened kittens
    Shepherd, R. K. ; Matsushima, J. ; Martin, R. L. ; Clark, Graeme M. ( 1994)
    The present study examines the effects of long-term electrical stimulation of the auditory nerve on cochlear histopathology and spiral ganglion cell survival in young sensorineural deafened cats. Eight kittens were deafened using kanamycin and ethacrynic acid, and implanted with bipolar or monopolar scala tympani electrodes. Following recovery from surgery the animals were unilaterally stimulated using charge balanced biphasic current pulses for 450-1730 hours over implant periods of up to four months. Charge densities varied from 0.6-0.9 µC.cm ^-2 geom. per phase for monopolar electrodes to 12-26 µC.cm ^-2 geom. per phase for the bipolar electrodes. Electrically-evoked auditory brainstem responses (EABRs) were periodically monitored during stimulation to confirm that the stimulus levels were above threshold, and to monitor any change in the response of the auditory nerve. Following completion of the stimulation program cochleae were prepared for histological examination. EABRs exhibited relatively stable thresholds for both stimulated and implanted, unstimulated control cochleae for the stimulus duration. While the growth in response amplitude as a function of stimulus current remained stable for the bipolar control and monopolar stimulated cochleae, the five cochleae chronically stimulated using bipolar electrodes exhibited a moderate to large increase in response amplitude. These increases were associated with a more widespread fibrous tissue response which may have altered the current distribution within these cochleae. Implanted control cochleae exhibited significantly less tissue response within the scala tympani. Importantly, we observed no statistically significant difference in the spiral ganglion cell density associated with chronic electrical stimulation when compared with unstimulated control cochleae. While the present study supports the safe application of cochlear implants in young profoundly deafened children, it does not corroborate previous studies that have reported electrical stimulation providing a trophic effect on degenerating auditory nerve fibres.
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    Partial hearing loss in the macaque following the co-administration of kanamycin and ethacrynic acid
    Shepherd, R. K. ; Xu, S. A. ; Clark, Graeme M. ( 1994)
    Co-administration of kanamycin (KA) with the loop diuretic ethacrynic acid (EA) rapidly produces a profound hearing loss in the cat while maintaining normal renal function [Xu et al., Hear. Res. 70, 205-215 (1993)]. In the present paper we have applied this deafening procedure to the old world monkey Macaca fascicularis (macaque). Following the co-administration of KA and EA, the hearing loss in the macaque developed far slower than we observed in the cat. Moreover, unlike the cat, there was evidence of a partial recovery in the animal’s hearing, resulting in a bilaterally symmetrical high frequency hearing loss. The extent of this hearing loss was dependent on the dose of the EA administered. Finally, the most unexpected result of the present study was the degree of acute nephrotoxicity experienced by these animals following the drug administration. The sensitivity of this species to renal failure restricted the dose of EA that could be safely administered. In conclusion, the co-administration of KA and EA cannot reliably produce a profound hearing loss in the macaque. While it can produce a dose dependent high frequency hearing loss the animal will also experience acute renal failure that requires careful management.
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    Cochlear pathology following chronic electrical stimulation using non charge balanced stimuli
    Shepherd, Robert K. ; Matsushima, Jun-Ichi ; Millard, R. E. ; Clark, Graeme M. ( 1991)
    During the course of a chronic intracochlear electrical stimulation study using charge balanced biphasic current pulses, one animal inadvertently received a short period of direct current (DC) stimulation at a level of approximately 1 µA. Subsequent, the animal was chronically stimulated using a poorly charge balanced waveform that produced a DC level of approximately 2 µA. Extensive pathological changes were observed within the cochlea. These changes included widespread spiral ganglion cell loss and new bone growth that extended throughout all turns of the cochlea. Significant changes in the morphology of the electrically evoked auditory brainstem response (EABR) were associated with these pathological changes. EABRs recorded prior to the DC stimulation exhibited a normal waveform morphology. However, responses recorded during the course of the DC stimulation were dominated by a short latency response believed to be vestibular in origin. The response thresholds were also significantly higher than levels recorded before the DC stimulation. In contrast, the contralateral cochlea, stimulated using charge balanced stimuli, showed no evidence of adverse pathological changes. Furthermore, EABRs evoked from this cochlea remained stable throughout the chronic stimulation period. Although preliminary, the present results illustrate the adverse nature of poorly charge balanced electrical stimuli. These results have important implications for both the design of neural prostheses and the use of DC stimuli to suppress tinnitus in patients.
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    Evaluation of a sealing device for the intracochlear electrode entry point
    PURSER, SIMON ; Shepherd, Robert K. ; Clark, Graeme M. ( 1991)
    Experimental evidence in animals indicates that middle ear infection in the presence of an intracochlear electrode may result in widespread cochlear damage due to the passage of organisms or products of inflammation through the electrode entry point. In this paper, results are presented of a study undertaken to test the efficacy of a titanium electrode entry point seal designed by the principal author, to protect the implanted cochlea from the pathological effects of experimentally induced pneumococcal otitis media in five cats. lntracochlear electrodes were inserted into both cochleas of each cat, one side sealed with the device and the other side left unsealed, as is current operative practice in human cochlear implantation, as a control. After a minimum of twelve post-operative weeks, pneumococcal otitis media was successfully inoculated in all but one (control) middle ear, which was not inoculated due to accidental removal of the electrode. One week after inoculation the animals were sacrificed and cochleas removed for histological examination. Results of histological examination of the cochleas are presented together with bacteriological data. The results of microscopic examination of the bond interface between otic capsule bone and the titanium seal are presented.