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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    Physiological and histopathological effects of chronic intracochlear electrical stimulation
    Shepherd, R. K. ; Clark, Graeme M. ; Black, R. C. (Monash University Press, 1983)
    Direct and r.f. currents are known to result in destruction of neural tissue. However, it is now apparent that non-destructive electrical stimulation can be achieved by the use of biphasic pulsatile stimuli (Lilly, 1960; Mortimer et al., 1970; Hughes et al., 1980). Although maximum biologically safe stimulation regimes have yet to be clearly defined, the evidence of a number of investigators suggests that charge density per phase and charge injection per phase are important parameters when establishing biologically safe levels of electrical stimulation (Pudenz et al., 1975; Pudenz et al., 1977; Brown et al., 1977; Babb et al., 1977). Furthermore, considerable attention has been given to ensure that the stimulus is not producing adverse electrochemical reactions that could result in physical or toxic injury to the biological environment. Brummer et al. (1977) have defined the upper limit of electrochemically safe electrical stimulation for platinum electrodes as charge balanced biphasic pulses at a maximum charge density of 300 ?C/cm2 geom./phase.
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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.
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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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    Evoked responses in the auditory cortex of the congenitally deaf white cat following electrical stimulation of the cochlea [Abstract]
    Klinke, R. ; Shepherd, R. ; Hartmann, R. ( 1995)
    Knowledge of the functional status of central auditory structures is important when estimating possible benefits of cochlear implantation in the congenitally deaf. Thus far the performance of prelingually deaf adults following cochlear implantation has been disappointing. We have used congenitally deaf cats as a model for prelingual deafness. These animals are deaf from an early age as shown by longitudinal recordings of auditory brainstem responses. They were studied as adults (age 2 years). Under general anaesthesia the cochleae were electrically stimulated using the NUCLEUS-22 banded scala tympani electrode array. Recordings were made from the contralateral auditory cortex and inferior colliculus. Gross potentials, together with multi� and single-unit activities were recorded. Here we confine ourselves to gross potential recordings from the auditory cortex. The skull was opened over the auditory area and the cortex photographed. A computer-controlled 3-axes microdrive provided precise and reproducible positioning of the monopolar recording electrode. Gross potentials were evoked by electrical stimulation of the auditory nerve using bipolar electrodes 1/2, 7/8 or 1/8 (electrode 1 being the most apical). These potentials were recorded from both the cortical surface and at depths of up to 4 mm, amplified and band pass filtered (10 Hz to 10 kHz). The stimuli (0.2 ms biphasic pulses) evoked middle latency responses (10 - 20 ms) over the primary and secondary auditory areas. Thresholds were lowest using electrodes 1/8 (-24 dB re. 1 mApp). Narrower electrode configurations (1/2 and 7/8) were up to 15 dB less effective. The potentials evoked were mono-, bi- or triphasic in shape, depending on recording site. We observed little evidence of tonotopic cortical mapping of stimulation site (1/2 vs. 7/8). If present at all, potentials were considerably smaller when the recording electrode was placed outside the auditory areas. Moreover, threshold currents were far higher (40 dB). It is concluded that the auditory cortex of congenitally deaf animals receives specific information via stimulation of the auditory nerve.