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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    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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    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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    Electrical stimulation of the auditory nerve in deaf kittens: effects on cochlear nucleus morphology
    Matsushima, Jun-Ichi ; Shepherd, Robert K. ; Seldon, H. Lee ; Xu, Shi-Ang ; Clark, Graeme M. ( 1991)
    The present study examines the effects of long-term electrical stimulation of the auditory nerve on the morphology of neurons in the cochlear nucleus in young, sensorineural deaf animals. Kittens, systemically deafened using kanamycin and ethacrynic acid, received bilateral cochlear implants and were stimulated unilaterally for periods of up to four months. After sacrifice, cross-sectional areas of neuron somata were measured with an image-analysis system and compared using nonparametric statistics. The areas of cell somata within the anteroventral cochlear nucleus (AVCN) on the stimulated side were significantly larger than those of corresponding somata on the control, unstimulated side (P < 0.001). However, there was no statistically significant difference among dorsal cochlear nucleus (DCN) neurons. These results indicate that long-term electrical stimulation of the auditory nerve can at least partially negate some effects of early postnatal auditory deprivation at the level of the cochlear nucleus.
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    Physiological and histopathological effects of chronic monopolar high rate stimulation on the auditory nerve
    TYKOCINSKI, MICHAEL ; Linahan, N. ; Shepherd, R. K. ; Clark, Graeme M. ( 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
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    Electrical stimulus induced changes in excitability of the auditory nerve
    Huang, C. O. ; Shepherd, Robert K. ; Seligman, P. M. ; Clark, Graeme M. ( 1997)
    High rate electrical stimulation of the auditory nerve using stimulus intensities well above the clinical limits can induce a significant reduction in the excitability of the auditory nerve as measured by a decrement in the amplitude of the electrically evoked auditory brainstem response (EABR). Two potential mechanisms may be associated with this stimulus induced reduction in activity: 1) stimulus induced prolonged neuronal hyperactivity; and 2) the generation of adverse electrochemical productions from the electrode surface. The purpose of the present study was to assess the extent to which adverse electrochemical damage contributes to the stimulus induced reduction in auditory nerve excitability. Twenty-six adult guinea pigs anaesthetized with ketamine (40 mg/kg i.p.) and xylazine (4 mglkg i.p.), were bilaterally implanted and unilaterally stimulated for two hours using a stimulus intensity of two or four times EABR threshold. Stimulus rates of 200, 400, or 1000 pulses/s (pps) were delivered via a standard platinum scala tympani electrode or large surface area ("high Q") platinum electrode.
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    Electrical stimulation of the auditory nerve: comparison of half-band with full-band scala tympani bipolar electrodes
    Xu, Shi-Ang ; McAnally, Ken I. ; Xu, J. ; Shepherd, R. K. ; Clark, Graeme M. ( 1993)
    The Melbourne/Cochlear auditory prosthesis uses an intracochlear electrode array containing 22 circumferential full-band electrodes mounted on a Silastic carrier. It could be hypothesized that half-band electrodes, oriented towards the modiolus, would produce lower stimulus thresholds than conventional full-band electrodes. This hypothesis is based on the assumption that, compared with full-band electrodes, half-band electrodes would produce an electrical field in which a greater proportion of the current would excite a defined group of neurons. In order to verify this hypothesis we recorded electrically evoked auditory brainstem responses (EABRs) for both full- and half-band electrodes inserted in the scala tympani of deafened cats. EABR thresholds for half-band electrodes oriented towards the modiolus were not significantly different from thresholds evoked using full-band electrodes (p>0.05, paired t-test), whereas thresholds evoked using half-band electrodes oriented towards the outer scala wall were significantly higher (p<0.01) than either the modiolar half-band or the full-band electrodes. These physiological results suggest that the electrical field generated within the auditory nerve by modiolar oriented half-band electrodes does not differ significantly from that produced by full-band electrodes. On the basis of these results, together with the fact that half-band electrodes would have higher current densities and electrode impedances, and would require careful orientation during implantation, we consider that there is no benefit in incorporating half-band electrodes in the design of scala tympani electrode arrays.