Graeme Clark Collection
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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.
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ItemEffects of chronic electrical stimulation on spiral ganglion neuron survival and size in deafened kittens( 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.