Graeme Clark Collection
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ItemEffects of intracochlear factors on spiral ganglion cells and auditory brain stem response after long-term electrical stimulation in deafened kittens( 2000)Using an animal model, we have studied the response of the auditory brain stem to cochlear implantation and the effect of intracochlear factors on this response. Neonatally, pharmacologically deafened cats (100 to more than 180 days old) were implanted with a 4-electrode array in both cochleas. Then, the left cochlea of each cat was electrically stimulated for total periods of up to 1000 hours. After a terminal 14C-2-deoxyglucose (2DG) experiment, the fraction of the right inferior colliculus with a significant accumulation of 2DG label was calculated. Using 3-dimensional computer-aided reconstruction, we examined the cochleas of these animals for spiral ganglion cell (SGC) survival and intracochlear factors such as electrode positions, degeneration of the organ of Corti, and the degree of fibrosis of the scala tympani. The distribution of each parameter was calculated along the organ of Corti from the basal end. There was a positive correlation between SGC survival and the level of fibrosis in the scala tympani, and a negative correlation between SGC survival and the degree of organ of Corti degeneration. Finally, there was a negative correlation between the 2DG-labeled inferior colliculus volume fraction and the degree of fibrosis, particularly in the 1-mm region nearest the pair of electrodes, and presumably in the basal turn.
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ItemComparison of electrode position in the human cochlea using various perimodiolar electrode arrays( 2000)Objective: This study was conducted to evaluate the insertion properties and intracochlear trajectories of three perimodiolar electrode array designs and to compare these designs with the standard Cochlear /Melbourne array. Background: Advantages to be expected of a perimodiolar electrode array include both a reduction in stimulus thresholds and an increase in dynamic range, resulting in a more localized stimulation pattern of the spiral ganglion cells, reduced power consumption, and, therefore, longer speech processor battery life. Methods: The test arrays were implanted into human temporal bones. Image analysis was performed on a radiograph taken after the insertion. The cochleas were then histologically processed with the electrode array in situ, and the resulting sections were subsequently assessed for position of the electrode array as well as insertion-related intracochlear damage. Results: All perimodiolar electrode arrays were inserted deeper and showed trajectories that were generally closer to the modiolus compared with the standard electrode array. However, although the precurved array designs did not show significant insertion trauma, the method of insertion needed improvement. After insertion of the straight electrode array with positioner, signs of severe insertion trauma in the majority o fimplanted cochleas were found. Conclusions: Although it was possible to position the electrode arrays close to the modiolus, none of the three perimodiolar designs investigated fulfilled satisfactorily all three criteria of being easy, safe, and a traumatic to implant.
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ItemChronic electrical stimulation of the auditory nerve at high stimulus rates: a physiological and histopathological study( 1997)A major factor associated with recent improvements in the clinical performance of cochlear implant patients has been the development of speech-processing strategies based on high stimulation rates. While these processing strategies show clear clinical advantage, we know little of their long-term safety implications. The present study was designed to evaluate the physiological and histopathological effects of long-term intracochlear electrical stimulation using these high rates. Thirteen normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods of up to 2100 h using either two pairs of bipolar or three monopolar stimulating electrodes. Stimuli consisted of short duration (25-50 µs/phase) charge-balanced biphasic current pulses presented at 1000 pulses per second (pps) per channel for monopolar stimulation, and 2000 pps/channel for bipolar stimulation. The electrodes were shorted between current pulses to minimize any residual direct current, and the pulse trains were presented using a 50% duty cycle (500 ms on; 500 ms oft) in order to simulate speech. Both acoustic (ABR) and electrical (EABR) auditory brainstem responses were recorded periodically during the chronic stimulation program, All cochleas showed an increase in the click-evoked ABR threshold following implant surgery; however, recovery to near-normal levels occurred in approximately half of the stimulated cochleas 1 month post-operatively. The use of frequency-specific stimuli indicated that the most extensive hearing loss generally occurred in the high-frequency basal region of the cochlea (12 and 24 kHz) adjacent to the stimulating electrode. However, thresholds at lower frequencies (2, 4 and 8 kHz), appeared at near-normal levels despite long-term electrode implantation and electrical stimulation. Our longitudinal EABR results showed a statistically significant increase in threshold in nearly 40% of the chronically stimulated electrodes evaluated; however, the gradient of the EABR input/output (I/O) function (evoked potential response amplitude versus stimulus current) generally remained quite stable throughout the chronic stimulation period. Histopathological examination of the cochleas showed no statistically significant difference in ganglion cell densities between cochleas using monopolar and bipolar electrode configurations (P = 0.67), and no evidence of cochlear damage caused by high-rate electrical stimulation when compared with control cochleas. Indeed, there was no statistically significant relationship between spiral ganglion cell density and electrical stimulation (P = 0.459), or between the extent of loss of inner (IHC, P = 0.86) or outer (OHC, P=0.30) hair cells and electrical stimulation. Spiral ganglion cell loss was, however, influenced by the degree of inflammation (P=0.016) and electrode insertion trauma. These histopathological findings were consistent with the physiological data. Finally, electrode impedance, measured at completion of the chronic stimulation program, showed close correlation with the degree of tissue response adjacent to the electrode array. These results indicated that chronic intracochlear electrical stimulation, using carefully controlled charge-balanced biphasic current pulses at stimulus rates of up to 2000 pps/channel, does not appear to adversely affect residual auditory nerve elements or the cochlea in general. This study provides an important basis for the safe application of improved speech-processing strategies based on high-rate electrical stimulation.
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ItemReduction in excitability of the auditory nerve following electrical simulation at high stimulus rates. II. Comparison of fixed amplitude with amplitude modulated stimuli( 1997)We have previously shown that acute electrical stimulation of the auditory nerve using charge-balanced biphasic current pulses presented continuously can lead to a prolonged decrement in auditory nerve excitability (Tykocinski et al., Hear. Res. 88 (1995), 124-142). This work also demonstrated a reduction in electrically evoked auditory brainstem response (EABR) amplitude decrement when using an otherwise equivalent pulse train with a 50% duty cycle. In the present study we have extended this work in order to compare the effects of electrical stimulation using both fixed amplitude electrical pulse trains and amplitude modulated (AM) pulse trains that more accurately model the dynamic stimulus paradigms used in cochlear implants. EABRs were recorded from guinea pigs following acute stimulation using AM trains of charge-balanced biphasic current pulses. The extent of stimulus-induced reductions in the EABR were compared with our previous results using either fixed amplitude continuous, or 50% duty cycle pulse trains operating at 0.34 µC/phase (2 mA, 170 µs/phase) at 400 or 1000 pulses/s (Tykocinski et al., Hear. Res. 88 (1995) 124-142). The AM pulse train, operating at the same rates, was based on a I-s sequence of the most extensively activated electrode of a Nucleus Mini-22 cochlear implant using the SPEAK speech processing strategy exposed to 4-talker babble, and delivered the same total charge as the fixed amplitude 50% duty cycle pulse train. Two hours of continuous stimulation induced a significant, rate-dependent reduction in auditory nerve excitability, and showed only a slight post-stimulus recovery for monitoring periods of up to 6 hours. Following 2 or 4 h of stimulation using an otherwise equivalent pulse train with a 50% duty cycle or the AM pulse train, significantly less reduction in the EABR was observed, and recovery to pre-stimulus levels was generally rapid and complete. These differences in the extent of the recovery between the continuous waveform and both the 50% duty cycle and AM waveforms were statistically significant for both 400 and 1000 pulses/s stimuli. Consistent with our previous results, the stimulus changes observed using AM pulse trains were rate dependent, with higher rate stimuli evoking more extensive stimulus-induced changes. The present findings show that while stimulus-induced reductions in neural excitability are dependent on the extent of stimulus-induced neuronal activity, the use of an AM stimulus paradigm further reduces post-stimulus neural fatigue.
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ItemLIF potentiates the NT-3-mediated survival of spiral ganglia neurones in vitro( 1997)The survival of auditory neurones depends on the continued supply of trophic factors. Early postnatal spiral ganglion cells (SGC) in a dissociated cell culture were used as a model of auditory innervation to test the trophic factors leukaemia inhibitory factor (LIF) and neurotrophin-3 (NT-3) for their ability, individually or in combination, to promote neuronal survival. The findings suggest that LIF supports neuronal survival in a concentration-dependent manner. Moreover LIF potentiated NT-3-mediated spiral ganglion neuronal survival in a synergistic fashion.
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ItemBiological safety(Singular Publishing, 1997)Biological safety has been extensively studied at the Department of Otolaryngology, The University of Melbourne, for cochlear implantation in adults, and subsequently for specific issues in infants and young children. Many of the studies have general applicability to cochlear implantation, but some have specific relevance to the Nucleus (Cochlear Limited) multiple-channel cochlear implant systems, and have been fundamental to their approval by the U.S. Food and Drug Administration (FDA). The Nucleus system was first approved by the FDA as safe and effective for postlinguistically deaf adults in October 1985, and 5 years later, on 27 June 1990, was approved for use in children from 2 years of age and older. The general research questions studied for adults are directly relevant for children and infants, but there are also specific questions that need to be answered when operating on children under 2 years of age.
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ItemThe neurotrophins act synergistically with LIF and members of the TGF-β superfamily to promote the survival of spiral ganglia neurons in vitro( 1999)Unavailable due to copyright.
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ItemClinical findings for a group of infants and young children with auditory neuropathy( 1999)Objective: To examine the prevalence of auditory neuropathy in a group of infants at risk for hearing impairment and to present an overview of the clinical findings for affected children. Design: Results for 20 subjects who showed repeatable cochlear microphonic potentials in the absence of click-evoked auditory brain stem responses are included in this study. Behavioral and steady state evoked potential thresholds were established in each case. Where possible, otoacoustic emission and speech perception results (unaided and aided) also were obtained. Results: One in 433 (0.23%) of the children in our series had evidence of auditory neuropathy. The audiometric findings for these subjects varied significantly, with behavioural thresholds ranging from normal to profound levels. Discrimination skills were also variable. Approximately half of the subjects showed little understanding, or even awareness, of speech inputs in both the unaided and aided conditions. There were, however, a number of children who could score at significant levels on speech discrimination tasks and who benefited from the provision of amplification. Conclusion: The results suggest that auditory neuropathy is more common in the infant population than previously suspected. The effects of neuropathy on auditory function appear to be idiosyncratic, producing significant variations in both the detection and discrimination of auditory signals. As such, the management of children with this disorder must allow for individual differences.
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ItemChronic electrical stimulation of the auditory nerve using non-charge-balanced stimuli( 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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ItemSynergy between TGF-ß3 and NT-3 to promote the survival of spiral ganglia neurones in vitro( 1998)Transforming growth factor-βs (TGF-βs) have been implicated in normal inner ear development and in promoting neuronal survival. Early rat post-natal spiral ganglion cells (SGC) in dissociated cell culture were used as a model of auditory innervation to test the trophic factors TGF-βs and neurotrophin-3 (NT-3) for their ability, individually or in combination, to promote neuronal survival. The findings from this study suggest that TGF-βs supports neuronal survival in a concentration-dependent manner. Moreover TGF-βs and NT-3-potentiated spiral ganglion neuronal survival in a synergistic fashion.