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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    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.
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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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    Scanning electron microscopy of chronically stimulated platinum intracochlear electrodes
    Shepherd, R. K. ; Murray, M. T. ; Houghton, M. E. ; Clark, Graeme M. ( 1985)
    Platinum electrodes were examined for evidence of corrosion using a scanning electron microscope (SEM). In vivo electrodes stimulated using charge-balanced biphasic pulses for periods of up to 2000 h at charge densities of 0.18-0.32 µC mm-2 geom. per phase, were compared with in vitro electrodes stimulated in inorganic saline using similar stimulus parameters, and with in vivo control electrodes. The in vitro stimulated electrodes showed evidence of platinum corrosion at high charge density and aggregate charge injection. Significantly, the in vivo stimulated electrodes showed no evidence of stimulus induced corrosion. Indeed, their surfaces were similar to the in vivo control electrodes. In vitro electrochemical studies have demonstrated that proteins play a significant role in the inhibition of platinum dissolution: the present study has demonstrated an inhibitory effect in vivo. This may be due to the presence of proteins.
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    The histopathological effects of chronic electrical stimulation of the cat cochlea
    Shepherd, R. K. ; Clark, Graeme M. ; Black, R. C. ; Patrick, J. F. (Cambridge University Press, 1983)
    The success of a cochlear implant depends on stimulating an adequate number of viable spiral ganglion cells. The effect of chronic electrical stimulation on ganglion cells is therefore an important consideration when assessing the effectiveness and safety of such a device. The histopathological assessment of chronic unstimulated intracochlear electrodes is now well documented (Simmons, 1967; Clark, 1973; Clark et al, 1975; Schindler and Merzenich, 1974; Schindler, 1976; Schindler et al, 1977; Sutton et al, 1980). These experimental studies have used a variety of electrode designs, materials and surgical techniques. However, all have shown that chronic implantation has little effect on the peripheral nerves and the spiral ganglion cells adjacent to an implant, provided the insertion procedure is free of trauma and infection.
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    Chronic electrical stimulation of the auditory nerve in cats: physiological and histopathological results
    Shepherd, R. K. ; Clark, Graeme M. ; Black, R. C. ( 1983)
    The ability of spiral ganglion cells to survive long-term electrical stimulation is a precondition for the success of cochlear prostheses. In this study 10 cats were implanted bilaterally with bipolar scala tympani electrodes and stimulated for periods of up to 2029 hours using charge balanced biphasic current pulses. The status of the auditory nerve was monitored periodically by recording electrically evoked auditory brainstem responses. At the conclusion of the stimulation program, spiral ganglion cell survival was assessed for stimulated and control cochleas; comparison of the two groups showed no statistically significant difference. The results of this study indicate that long-term intracochlear electrical stimulation using carefully controlled biphasic pulses does not adversely affect the spiral ganglion cell population.