Graeme Clark Collection

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    The multi-channel cochlear implant: past, present and future perspectives.
    Clark, G (Informa UK Limited, 2009)
    Initial research demonstrated that only low frequencies could be mimicked with rate of electrical stimulation, and thus multi-channel rather than single-channel stimulation was required for the place coding of the mid-high speech frequencies. Place coding of mid-high frequencies was best achieved with electrodes inside the cochlea. Furthermore, correct biomechanical properties of a multiple electrode bundle were required for it to pass around the cochlear spiral to the speech frequency region. Biological studies showed too that intra-cochlear electrodes could be used with minimal trauma, safe electrical stimulus parameters, and methods to prevent inner ear infection and meningitis. The crucial discoveries for coding speech with electrical stimulation have been based on the discovery of: 1) the fact the brain processes frequency information along spatial and temporal channels, and 2) that the first patient experienced vowels when stimulating different electrodes that corresponded to the place of excitation for single formant vowels in people with normal hearing. The inaugural and subsequent speech processing strategies extracted frequencies of special importance for speech intelligibility, and transmitted the information along place coding channels. The voicing frequency and/or amplitude, was coded as temporal information across these spatial channels. As a result a great majority of severely-to-profoundly deaf people with previous hearing can not only communicate when electrical stimulation is combined with lipreading, but with electrical stimulation alone. In addition, the benefits of binaural hearing with bilateral cochlear implants or an implant in one ear and hearing aid in the other ear have been realized. Related psychophysical research has discovered the basic perceptual skills that process the complex patterns of brain excitation that underlie speech recognition both in the one ear as well as bilateral implants.In addition the development of the perceptual skills in the maturing child for speech recognition, have been discovered. In the future high fidelity sound should be achieved by providing the fine temporo-spatial patterns of excitation and preserving the peripheral nerve network. This could require the release of nerve growth factors and the development of electrodes using nanotechnology.
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    Personal reflections on the multichannel cochlear implant and a view of the future
    Clark, GM (JOURNAL REHAB RES & DEV, 2008-01-01)
    The multichannel cochlear implant is the first neural prosthesis to effectively and safely bring electronic technology into a direct physiological relation with the central nervous system and human consciousness. It is also the first cochlear implant to give speech understanding to tens of thousands of persons with profound deafness and spoken language to children born deaf in more than 80 countries. In so doing, it is the first major advance in research and technology to help deaf children communicate since Sign Language of the Deaf was developed at the Paris deaf school (L'Institut National de Jeunes Sourds de Paris) >200 years ago. Furthermore, biomedical research has been fundamental for ensuring that the multielectrode implant is safe as well as effective. More recent research has also shown that bilateral implants confer the benefits of binaural hearing. Future research using nanotechnology should see high-fidelity sound received, which would help deaf persons communicate in noise and enjoy music. Research should also lead to implants in ears with useful hearing.
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    Can we prevent cochlear implant recipients from developing pneumococcal meningitis?
    Wei, BPC ; Robins-Browne, RM ; Shepherd, RK ; Clark, GM ; O'Leary, SJ (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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    Promoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodes
    Evans, AJ ; Thompson, BC ; Wallace, GG ; Millard, R ; O'Leary, SJ ; Clark, GM ; Shepherd, RK ; Richardson, RT (WILEY, 2009-10-01)
    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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    Fast inhibition alters first spike timing in auditory brainstem neurons
    Paolini, AG ; Clarey, JC ; Needham, K ; Clark, GM (AMER PHYSIOLOGICAL SOC, 2004-10-01)
    Within the first processing site of the central auditory pathway, inhibitory neurons (D stellate cells) broadly tuned to tonal frequency project on narrowly tuned, excitatory output neurons (T stellate cells). The latter is thought to provide a topographic representation of sound spectrum, whereas the former is thought to provide lateral inhibition that improves spectral contrast, particularly in noise. In response to pure tones, the overall discharge rate in T stellate cells is unlikely to be suppressed dramatically by D stellate cells because they respond primarily to stimulus onset and provide fast, short-duration inhibition. In vivo intracellular recordings from the ventral cochlear nucleus (VCN) showed that, when tones were presented above or below the characteristic frequency (CF) of a T stellate neuron, they were inhibited during depolarization. This resulted in a delay in the initial action potential produced by T stellate cells. This ability of fast inhibition to alter the first spike timing of a T stellate neuron was confirmed by electrically activating the D stellate cell pathway that arises in the contralateral cochlear nucleus. Delay was also induced when two tones were presented: one at CF and one outside the frequency response area of the T stellate neuron. These findings suggest that the traditional view of lateral inhibition within the VCN should incorporate delay as one of its principle outcomes.
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    Wet-Spun Biodegradable Fibers on Conducting Platforms: Novel Architectures for Muscle Regeneration
    Razal, JM ; Kita, M ; Quigley, AF ; Kennedy, E ; Moulton, SE ; Kapsa, RMI ; Clark, GM ; Wallace, GG (WILEY-V C H VERLAG GMBH, 2009-11-09)
    Novel biosynthetic platforms supporting ex vivo growth of partially differentiated muscle cells in an aligned linear orientation that is consistent with the structural requirements of muscle tissue are described. These platforms consist of biodegradable polymer fibers spatially aligned on a conducting polymer substrate. Long multinucleated myotubes are formed from differentiation of adherent myoblasts, which align longitudinally to the fiber axis to form linear cell-seeded biosynthetic fiber constructs. The biodegradable polymer fibers bearing undifferentiated myoblasts can be detached from the substrate following culture. The ability to remove the muscle cell-seeded polymer fibers when required provides the means to use the biodegradable fibers as linear muscle-seeded scaffold components suitable for in vivo implantation into muscle. These fibers are shown to promote differentiation of muscle cells in a highly organized linear unbranched format in vitro and thereby potentially facilitate more stable integration into recipient tissue, providing structural support and mechanical protection for the donor cells. In addition, the conducting substrate on which the fibers are placed provides the potential to develop electrical stimulation paradigms for optimizing the ex vivo growth and synchronization of muscle cells on the biodegradable fibers prior to implantation into diseased or damaged muscle tissue.
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    Research directions for future generations of cochlear implants.
    Clark, G (Maney Publishing, 2004-09)
    Physiological and psychophysical research indicates that improved hearing in noise and music appreciation are likely with cochlear implants, with better reproduction of the fine temporospatial patterns of neural response in the auditory pathways due to phase differences in neuron firing patterns as the result of the basilar membrane travelling wave. An initial speech-processing strategy, to in part reproduce this information, is showing better frequency discrimination and musical perception. However, more exact reproduction is likely with a new generation electrode array which could involve the use of neurotrophins and inherently conducting polymers. The siting and design of this, as well as safety, needs further investigation before it is implemented.
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    Optimizing dynamic range in children using the nucleus cochlear implant
    Dawson, PW ; Decker, JA ; Psarros, CE (LIPPINCOTT WILLIAMS & WILKINS, 2004-06-01)
    OBJECTIVE: The aim of this study was to investigate the benefits of the preprocessing scheme "Adaptive Dynamic Range Optimization" (ADRO) in children using Nucleus cochlear implants. Previous research with adults indicates improved speech perception in quiet and improved sound quality in everyday listening environments with the ADRO scheme. DESIGN: Children were given 4 wk of take-home experience with ADRO, with a minimum of 2 wk in which ADRO was "locked-in." After 1 wk of ADRO use and again after 4 wk of ADRO use, Bench-Kowal-Bamford (BKB) sentence perception in quiet at a low input level of 50 dB SPL (unweighted root mean square) and sentence perception in noise were compared with the child's everyday (Standard) program and the ADRO program. Children also rated the loudness of a variety of environmental sounds and indicated which program provided the best hearing in a variety of everyday listening situations. RESULTS: On average, BKB sentence perception in quiet at 50 dB SPL was significantly better with the ADRO program compared with the Standard program. The group mean improvement was 8.60%. Similarly, group mean scores for BKB sentences presented at 65 dB SPL in multitalker babble were significantly higher with the ADRO program (an improvement of 6.87%). The ADRO program was the preferred program in 46% of the listening situations, whereas the Standard program was preferred in 26% of situations. Everyday sounds were not unacceptably loud with ADRO. CONCLUSIONS: There was an ADRO benefit for this group of children in quiet and in noise. These findings suggest that young children would benefit from the ADRO programming option being locked in along with other processor settings in the SPrint processor once their MAP levels have stabilized. Some older children and teenagers may choose to use ADRO selectively for specific listening situations.
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    A Conducting-Polymer Platform with Biodegradable Fibers for Stimulation and Guidance of Axonal Growth
    Quigley, AF ; Razal, JM ; Thompson, BC ; Moulton, SE ; Kita, M ; Kennedy, EL ; Clark, GM ; Wallace, GG ; Kapsa, RMI (WILEY-V C H VERLAG GMBH, 2009-11-20)
    A biosynthetic platform composed of a conducting polypyrrole sheet embedded with unidirectional biodegradable polymer fibers is described (see image; scale bar = 50 µm). Such hybrid systems can promote rapid directional nerve growth for neuro-regenerative scaffolds and act as interfaces between the electronic circuitry of medical bionic devices and the nervous system.
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    Polypyrrole-coated electrodes for the delivery of charge and neurotrophins to cochlear neurons
    Richardson, RT ; Wise, AK ; Thompson, BC ; Flynn, BO ; Atkinson, PJ ; Fretwell, NJ ; Fallon, JB ; Wallace, GG ; Shepherd, RK ; Clark, GM ; O'Leary, SJ (ELSEVIER SCI LTD, 2009-05-01)
    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.