Graeme Clark Collection

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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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    Post mortem study of the intracochlear position of the nucleus standard 22 electrode array
    XU, JIN ; Dahm, M. C. ; Tykocinski, Michael. ; Shepherd, Robert K. ; Clark, Graeme M. ( 2000)
    The final position of an intracochlear cochlear implant electrode array can vary depending on the pathology, the insertion technique used and the type of electrode array used. The distance of the electrodes from the target neural elements and the presence of intracochlear fibrous tissue or new bone formation are believed to affect the performance of the device. A post mortem study was conducted to assess these factors.
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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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    Effects of sensorineural hearing loss on the refractory properties of auditory nerve fibers
    Roberts, L. A. ; Shepherd, R. K. ; Paolini, A. G. ; Clark, Graeme M. ; Burkitt, A. N. ( 2000)
    We hypothesised that the loss of the peripheral processes and the partial demyelination of auditory nerve fibres (ANFs) following a sensorineural hearing loss would increase their refractory properties. Normal control, and long-term (2.5 months) systemically deafened rats were anaesthetised (urethane, 1.3 g/kg i.p.), a bipolar stimulating electrode was implanted into the scala tympani and glass microelectrodes (30-80 MΩ) used to record single ANF activity. Stimuli (pairs of 100 µs/phase charge balanced biphasic pulses with interpulse intervals (IPIs) of 0.34-10 ms) were presented at 6 dB above threshold using a repetition interval of 250 ms. Absolute refractory period (ARP) was defined as the IPI at which the probability of eliciting a spike to the second stimulus was 0.1. In the present results, based on recordings from 62 fibres, ANFs were distinguished from cochlear nucleus (CN) neurones by their significantly shorter median latencies (AN: 0.575ms vs CN: 1.137ms; Whitney-Mann Rank Sum, p<0.0001). There were no significant differences between minimum ANF latencies from normal and deafened animals. Although the median ARP was greater in deafened versus normal animals, this difference was not statistically significant (normals: median0.658ms, interquartile range 0.554-0.913ms; deafened: 0.772ms and 0.616-1.073ms; p=0.16). Finally, the spike latency associated with the second pulse of a pair systematically increased with decreasing IPI, contrasting with the stable latency of the response to the leading pulse. Although pathological changes to ANFs may increase their refractory properties, at this duration of deafness these changes were not significant.
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    Electrical stimulation of the auditory nerve: chronic monopolar stimulation using very high stimulus rates [Abstract]
    Tykocinski, M. ; Linahan, N. ; Shepherd, Robert K. ; Clark, Graeme M. ( 1998)
    Speech processing strategies based on high rate electrical stimulation have been associated with recent improvements of speech perception among cochlear implant users. In the present study we investigated the effects of chronic monopolar stimulation using very high rates (14493 pulses\s). Under general anaesthesia (ketamine (20 mg/kg) and xylazine (3.8 mg/kg) i.p.) six normal hearing cats were implanted bilaterally with a three channel platinum (Pt) scala tympani electrode array, while a return Pt-electrode was placed outside the bulla. Chronic electrical stimulation using charge-balanced biphasic current pulses was delivered unilaterally via a transcutaneous leadwire connected to a backpack-stimulator for up to 2000 h. The animals hearing status was periodically monitored using acoustically evoked compound action potentials (CAP's) and brainstem responses (ABR's). In addition the electrically evoked ABR (EABR) was also recorded to ensure that the chronic stimulus was above threshold. Stimulus current and electrode voltage waveforms were monitored twice daily and access resistance (Ra) and electrode impedance (Zc) calculated. ABR and CAP thresholds were elevated immediately following implantation, but generally showed evidence of partial recovery (0-40 dB). Further deterioration of thresholds on the stimulated side (10-30 dB) was subsequently observed, while control-thresholds remained more stable. Ra (1.3-1.8 kΩ) and Zc (2.2-3.8Ω) typically increased in the first few weeks of electrical stimulation up to Ra:5.6 kΩ and Zc:8.1 kΩ, before decreasing slightly to a constant plateau. These initial results indicate changes in the electrode-tissue interface and tissue growth within the cochlea. They also indicate that chronic stimulation at these high rates may decrease residual hearing.
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    Increased survival of auditory neurones treated with LIF
    Marzella, P. L. ; Clark, Graeme M. ; Shepherd, R. K. ; Bartlett, P. F. ; Kilpatrick, T. J. ( 1997)
    Degeneration of spiral ganglion cells (SOC) is one of the most common correlates of sensorineural hearing loss (1). Several lines of evidence show that the continued supply of growth factors is responsible for maintaining auditory neurone integrity (2). In the present study SOC cultures were used as a model of auditory innervation to test the ability of the cytokine leukaemia inhibitory factor (LIF) and the neurotrophin NT -3 to promote neuronal survival individually or in combination. The data demonstrate that LIF promotes the survival of SOC in a concentration-dependent manner, with a significant increase in neuronal survival at concentrations as low as 0.1 ng/ml compared to untreated wells ( p< 0.05), and a maximum neuronal survival at 10 ng/ml. In addition, when used in combination LIF and NT-3 were more effective in promoting neuronal survival than either factor individually, with a significant increase in survival at concentrations of 0.1ng mI[to the power of]-1/0.1 ng mI[to the power of]-1 (LIF/NT-3). To our knowledge this is the first study reporting that LIF has trophic activity on SOC. Moreover, the data suggest that a combination of several growth factors may provide a better approach when developing pharmacological therapies for auditory neuron repair.
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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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    Decrement in auditory nerve function following acute high rate stimulation using various stimulus paradigms in guinea pigs [Abstract]
    Tykocinski, M. ; Shepherd, R. K. ; Clark, Graeme M. ( 1996)
    Previous experimental studies have shown that chronic electrical stimulation of the auditory nerve using charge balanced biphasic current pulses at rates of up to 500 pulses per second (pps) do not adversely affect the adjacent spiral ganglion population. More recently psychophysical trials have indicated that speech processing strategies based on high pulse rates (1000 pps or more) can improve speech perception in cochlea implant patients. In this paper we summarize the results following acute high rate stimulation using different stimulus paradigms.