Graeme Clark Collection
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ItemNo Preview AvailableCan we prevent cochlear implant recipients from developing pneumococcal meningitis?(Oxford University Press (OUP), 2008-01-01)The restoration of hearing to persons with severely or profoundly impaired hearing by means of a cochlear implant is one of the great achievements of bionics applied to medicine. However, pneumococcal meningitis in implant recipients has received high profile public attention as a result of the US Food and Drug Administration's public health notification and recent media attention. Worldwide, 118 of the 60,000 people who received cochlear implants over the past 20 years have acquired meningitis, causing deep concern in the international medical community. This review provides answers to pediatricians, internists, and infectious diseases doctors who have patients with cochlear implants and who have questions about the safety of the cochlear implant from both the clinical and scientific research perspectives. Both clinical and laboratory research support the notion that pneumococcal meningitis is more likely in patients who receive cochlear implantation, and that the surgical insertion technique and the cochlear implant design should be nontraumatic, and that all cochlear implant recipients should be offered vaccination against Streptococcus pneumoniae.
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ItemPromoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodes(WILEY, 2009-10)Release of neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF) from hair cells in the cochlea is essential for the survival of spiral ganglion neurons (SGNs). Loss of hair cells associated with a sensorineural hearing loss therefore results in degeneration of SGNs, potentially reducing the performance of a cochlear implant. Exogenous replacement of either or both neurotrophins protects SGNs from degeneration after deafness. We previously incorporated NT3 into the conducting polymer polypyrrole (Ppy) synthesized with para-toluene sulfonate (pTS) to investigate whether Ppy/pTS/NT3-coated cochlear implant electrodes could provide both neurotrophic support and electrical stimulation for SGNs. Enhanced and controlled release of NT3 was achieved when Ppy/pTS/NT3-coated electrodes were subjected to electrical stimulation. Here we describe the release dynamics and biological properties of Ppy/pTS with incorporated BDNF. Release studies demonstrated slow passive diffusion of BDNF from Ppy/pTS/BDNF, with electrical stimulation significantly enhancing BDNF release over 7 days. A 3-day SGN explant assay found that neurite outgrowth from explants was 12.3-fold greater when polymers contained BDNF (p < 0.001), although electrical stimulation did not increase neurite outgrowth further. The versatility of Ppy to store and release neurotrophins, conduct electrical charge, and act as a substrate for nerve-electrode interactions is discussed for specialized applications such as cochlear implants.
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ItemNo Preview AvailablePolypyrrole-coated electrodes for the delivery of charge and neurotrophins to cochlear neurons(ELSEVIER SCI LTD, 2009-05)Sensorineural hearing loss is associated with gradual degeneration of spiral ganglion neurons (SGNs), compromising hearing outcomes with cochlear implant use. Combination of neurotrophin delivery to the cochlea and electrical stimulation from a cochlear implant protects SGNs, prompting research into neurotrophin-eluting polymer electrode coatings. The electrically conducting polypyrrole/para-toluene sulfonate containing neurotrophin-3 (Ppy/pTS/NT3) was applied to 1.7 mm2 cochlear implant electrodes. Ppy/pTS/NT3-coated electrode arrays stored 2 ng NT3 and released 0.1 ng/day with electrical stimulation. Guinea pigs were implanted with Ppy/pTS or Ppy/pTS/NT3 electrode arrays two weeks after deafening via aminoglycosides. The electrodes of a subgroup of these guinea pigs were electrically stimulated for 8 h/day for 2 weeks. There was a loss of SGNs in the implanted cochleae of guinea pigs with Ppy/pTS-coated electrodes indicative of electrode insertion damage. However, guinea pigs implanted with electrically stimulated Ppy/pTS/NT3-coated electrodes had lower electrically-evoked auditory brainstem response thresholds and greater SGN densities in implanted cochleae compared to non-implanted cochleae and compared to animals implanted with Ppy/pTS-coated electrodes (p<0.05). Ppy/pTS/NT3 did not exacerbate fibrous tissue formation and did not affect electrode impedance. Drug-eluting conducting polymer coatings on cochlear implant electrodes present a clinically viable method to promote preservation of SGNs without adversely affecting the function of the cochlear implant.
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ItemHistopathology of the binaural cochlear implant subject [Abstract]( 2001)Binaural hearing improves speech reception in noise, and is necessary for sound localisation. Normal hearing subjects use both interaural time, and intensity, differences to localise sound. This study investigates why sound localisation in bilateral cochlear implantees is insensitive to interaural time differences (Hoesel 1993). We looked for evidence of neural degeneration in the auditory brainstem involved in binaural sound localisation, since this may have degraded the neural circuitry required to accurately code interaural time delays. Method: The brainstem of a bilateral cochlear implantee was prepared for light microscopy by embedding it in paraffin, sectioning at 10 mm and staining sections with thionine or Luxol fast blue (LFB). The histological sections were digitised with NIH Image and 3-dimensional reconstructions made of the cochlear nucleus (CN) and superior olivary complex (SOC) with AnalysePC. Within the CN and the SOC, cell number and size were estimated by the physical dissector technique following thionine staining, and myelination of the nerve fibres was estimated using the optical density method following LFB staining. Results: A reduction in cell size (from thionine staining) and myelination (from LFB staining) was seen in both the CN and the SOC. Conclusions: These finding are consistent with neural degeneration within the auditory pathways. This may have lead to a degradation of the neural circuitry required to accurately detect interaural time delays.
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ItemThe effects of stochastic neural activity in a model predicting intensity perception with cochlear implants: low-rate stimulation( 1999)Most models of auditory nerve response to electrical stimulation are deterministic, despite significant physiological evidence for stochastic activity. Furthermore, psychophysical models and analyses of physiological data using deterministic descriptions do not accurately predict many psychophysical phenomena. In this paper we investigate whether inclusion of stochastic activity in neural models improves such predictions. To avoid the complication of interpulse interactions and to enable the use of a simpler and faster auditory nerve model we restrict our investigation to single pulses and low-rate (<200 pulses/s) pulse trains. We apply signal detection theory to produce direct predictions of behavioural threshold, dynamic range and intensity difference limen. Specifically, we investigate threshold versus pulse duration (the strength-duration characteristics), threshold and uncomfortable loudness (and the corresponding dynamic range) versus phase duration, the effects of electrode configuration on dynamic range and on strength-duration, threshold versus number of pulses (the temporal-integration characteristics), intensity difference limen as a function of loudness, and the effects of neural survival on these measures. For all psychophysical measures investigated, the inclusion of stochastic activity in the auditory nerve model was found to produce more accurate predictions.
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ItemA stochastic model of the electrically stimulated auditory nerve: pulse-train response( 1999)The single-pulse model of the companion paper [1] is extended to describe responses to pulse trains by introducing a phenomenological refractory mechanism. Comparisons with physiological data from cat auditory nerve fibers are made for pulse rates between 100 and 800 pulses/s. First, it is shown that both the shape and slope of mean discharge rate curves are better predicted by the stochastic model than by the deterministic model. Second, while interpulse effects such as refractory effects do indeed increase the dynamic range at higher pulse rates, both the physiological data and the model indicate that much of the dynamic range for pulse-train stimuli is due to stochastic activity. Third, it is shown that the stochastic model is able to predict the general magnitude and behavior of variance in discharge rate as a function of pulse rate, while the deterministic model predicts no variance at all.
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ItemA stochastic model of the electrically stimulated auditory nerve: single-pulse response( 1999)Most models of neural response to electrical stimulation, such as the Hodgkin-Huxley equations, are deterministic, despite significant physiological evidence for the existence of stochastic activity. For instance, the range of discharge probabilities measured in response to single electrical pulses cannot be explained at all by deterministic models. Furthermore, there is growing evidence that the stochastic component of auditory nerve response to electrical stimulation may be fundamental to functionally significant physiological and psychophysical phenomena. In this paper we present a simple and computationally efficient stochastic model of single-fiber response to single biphasic electrical pulses, based on a deterministic threshold model of action potential generation. Comparisons with physiological data from cat auditory nerve fibers are made, and it is shown that the stochastic model predicts discharge probabilities measured in response to single biphasic pulses more accurately than does the equivalent deterministic model. In addition, physiological data show an increase in stochastic activity with increasing pulse width of anodic/cathodic biphasic pulses, a phenomenon not present for monophasic stimuli. These and other data from the auditory nerve are then used to develop a population model of the total auditory nerve, where each fiber is described by the single-fiber model.
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ItemDischarge rate-level functions from dorsal cochlear nucleus single units in response to acoustic and electrical stimulation of the auditory nerve( 1995)Discharge rate-level (I/O) functions possessed by dorsal cochlear nucleus (DCN) units were examined, in response to bipolar electrical stimulation of the cochlea of the barbiturate-anesthetized cat. Spontaneously active units usually possessed nonmonotonic functions with a minimum, and spontaneously inactive units usually possessed monotonic functions or nonmonotonic functions with a maximum (NM+). In response to acoustic high-pass filtered noise, the function relating discharge rate and cut off frequency resembled the same unit's I/O function to electrical stimulation. The I/O functions to acoustic characteristic tones were usually monotonic or NM+. These results suggest that in the DCN, a prerequisite for the generation of acoustic-like responses with an electrical stimulus may be the matching of the cochlear place and spatial extent activated by each stimulus.
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ItemResponses of dorsal cochlear nucleus single units to electrical pulse train stimulation of the auditory nerve with a cochlear implant electrode( 1995)Abstract not available due to copyright.
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ItemCurrent distributions of intracochlear electrodes in cats [Abstract](Monash University Press, 1983)A non-invasive technique, "two electrode mapping" has been developed to measure the current distribution of a multichannel electrode array within the feline scala tympani. An electrode’s current distribution is an important determinant of its ability to excite discrete neural groups. The electrode array, a “banded electrode” is a series of platinum rings, supported by a cylinder of silastic which fits freely into the scala tympani. All cats had normal hearing pre-operatively and were implanted through the round window. Hearing was normal within 10 dB after implantation, necessitating the presentation of 30-40 dB white noise to the implanted ear throughout experimentation to mask the electrophonic component (Black et al., 1983).