DSpace Angular :: Browsing by Author "Wise, Andrew"

Browsing by Author "Wise, Andrew"

Now showing 1 - 20 of 46

Anti-apoptotic gene Bcl2 is required for stapes development and hearing
(Macmillan Publishers Limited, 2012-08-09) Carpinelli, Marina; Wise, Andrew; Arhatari, Benedicta; Bouillet, Phillipe; Manji, Shehnaaz; Manning, Michael; Cooray, Anne; Burt, Rachel
In this paper we describe novel and specific roles for the apoptotic regulators Bcl2 and Bim in hearing and stapes development. Bcl2 is anti-apoptotic while Bim is pro-apoptotic. Characterization of the auditory systems of mice deficient for these molecules revealed that Bcl2 / mice suffered severe hearing loss. This was conductive in nature and did not affect sensory cells of the inner ear, with cochlear hair cells and neurons present and functional. Bcl2 / mice were found to have a malformed, often monocrural, porous stapes (the small stirrup-shaped bone of the middle ear), but a normally shaped malleus and incus. The deformed stapes was discontinuous with the incus and sometimes fused to the temporal bones. The defect was completely rescued in Bcl2 / Bim / mice and partially rescued in Bcl2 / Bimþ/ mice, which displayed high-frequency hearing loss and thickening of the stapes anterior crus. The Bcl2 / defect arose in utero before or during the cartilage stage of stapes development. These results implicate Bcl2 and Bim in regulating survival of second pharyngeal arch or neural crest cells that give rise to the stapes during embryonic development.
Biological Considerations of Optical Interfaces for Neuromodulation
(WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim, 2019-07) Hart, William; Kameneva, Tatiana; Wise, Andrew; Stoddart, Paul
The success of devices such as cochlear implants and pacemakers has led to increasing interest in new applications of artificial neural interfaces, ranging from brain–computer interfaces to vagus nerve stimulators. Both the established and emerging applications of neural interfaces have highlighted the need for improvements in spatial selectivity and reduced invasiveness, which in turn has driven growing interest in optical interfaces. The delivery of light to—and collection of light from—neural tissue presents distinct challenges for optical devices. This review presents the status of optical interface technologies with a focus on biological considerations, such as biocompatibility, thermal loading, and tissue response. Attention is also paid to factors affecting the portability of optical interfaces, and issues around reliability and manufacturing that need to be considered for successful translation. Indeed, it is imperative that engineers work closely with physiologists, clinicians, and patients when developing devices for research and the clinic. Finally, emerging trends and the potential for new technologies to disrupt the field are discussed. While many engineering challenges remain to be overcome, the achievements to date suggest that optical neuromodulation techniques have significant potential to be deployed in future for a wide range of practical therapeutic applications.
Challenges for the application of optical stimulation in the cochlea for the study and treatment of hearing loss
(Taylor and Francis, 2017-02) Richardson, Rachael; Thompson, Alexander; Wise, Andrew; Needham, Karina
INTRODUCTION: Electrical stimulation has long been the most effective strategy for evoking neural activity from bionic devices and has been used with great success in the cochlear implant to allow deaf people to hear speech and sound. Despite its success, the spread of electrical current stimulates a broad region of neural tissue meaning that contemporary devices have limited precision. Optical stimulation as an alternative has attracted much recent interest for its capacity to provide highly focused stimuli, and therefore, potentially improved sensory perception. Given its specificity of activation, optical stimulation may also provide a useful tool in the study of fundamental neuroanatomy and neurophysiological processes. Areas covered: This review examines the advances in optical stimulation - infrared, nanoparticle-enhanced, and optogenetic-based - and its application in the inner ear for the restoration of auditory function following hearing loss. Expert opinion: Initial outcomes suggest that optogenetic-based approaches hold the greatest potential and viability amongst optical techniques for application in the cochlea. The future success of this approach will be governed by advances in the targeted delivery of opsins to auditory neurons, improvements in channel kinetics, development of optical arrays, and innovation of opsins that activate within the optimal near-infrared therapeutic window.
Chronic intracochlear electrical stimulation at high charge densities results in platinum dissolution but not neural loss or functional changes in vivo
(IOP Publishing, 2019-01) Shepherd, Robert; Carter, Paul; Enke, Ya Lang; Wise, Andrew; Fallon, James
OBJECTIVE: Although there are useful guidelines defining the boundary between damaging and non-damaging electrical stimulation they were derived from acute studies using large surface area electrodes in direct contact with cortical neurons. These parameters are a small subset of the parameters used by neural stimulators. More recently, histological examination of cochleae from patients that were long-term cochlear implant users have shown evidence of particulate platinum (Pt). The pathophysiological effect of Pt within the cochlea is unknown. We examined the response of the cochlea to stimulus levels beyond those regarded as safe, and to evaluate the pathophysiological response of the cochlea following chronic stimulation at charge densities designed to induce Pt corrosion. APPROACH: 19 guinea pigs were systemically deafened and implanted with a cochlear electrode array containing eight Pt electrodes of 0.05 0.075 or 0.2 mm2 area. Animals were electrically stimulated continuously for 28 days using charge balanced current pulses at charge densities of 400, 267 or 100 muC/cm2/phase. Electrically-evoked auditory brainstem responses (EABRs) were recorded to monitor neural function. On completion of stimulation electrodes were examined using scanning electron microscopy (SEM) and cochleae examined histology. Finally, analysis of Pt was measured using Energy Dispersive X-ray Spectroscopy (EDS) and inductively coupled plasma mass spectrometry (ICP-MS). MAIN RESULTS: Compared with unstimulated control electrodes and electrodes stimulated at 100 muC/cm2/phase, stimulation at 267 or 400 muC/cm2/phase resulted in significant Pt corrosion. Cochleae stimulated at these high charge densities contained particulate Pt. The extent of the foreign body response depended on the level of stimulation; cochleae stimulated at 267 or 400 muC/cm2/phase exhibited an extensive tissue response that included a focal region of necrosis close to the electrode. Despite chronic stimulation at high charge densities there was no loss of auditory neurons (ANs) in stimulated cochleae compared with their contralateral controls. Indeed, we report a statistically significant increase in AN density proximal to electrodes stimulated at 267 or 400 muC/cm2/phase. Finally, there was no evidence of a reduction in AN function associated with chronic stimulation at 100, 267 or 400 muC/cm2/phase as evidenced by stable EABR thresholds over the stimulation program. SIGNIFICANCE: Chronic electrical stimulation of Pt electrodes at 267 or 400 muC/cm2/phase evoked a vigorous tissue response and produced Pt corrosion products that were located close to the electrode. Despite these changes at the electrode/tissue interface there was no evidence of neural loss or a reduction in neural function.
Cochlear implantation for chronic electrical stimulation in the mouse.
(Elsevier, 2013-12) Irving, Samuel; Trotter, Matthew; Fallon, James; Millard, Rodney; Shepherd, Robert; Wise, Andrew
The mouse is becoming an increasingly attractive model for auditory research due to the number of genetic deafness models available. These genetic models offer the researcher an array of congenital causes of hearing impairment, and are therefore of high clinical relevance. To date, the use of mice in cochlear implant research has not been possible due to the lack of an intracochlear electrode array and stimulator small enough for murine use, coupled with the difficulty of the surgery in this species. Here, we present a fully-implantable intracochlear electrode stimulator assembly designed for chronic implantation in the mouse. We describe the surgical approach for implantation, as well as presenting the first functional data obtained from intracochlear electrical stimulation in the mouse.
Combined optogenetic and electrical stimulation of auditory neurons increases effective stimulation frequency—an in vitro study
(IOP Publishing, 2020-01) Hart, William; Richardson, Rachael; Kameneva, Tatiana; Thompson, Alex; Wise, Andrew; Fallon, James; Stoddart, Paul; Needham, Karina
OBJECTIVE: The performance of neuroprostheses, including cochlear and retinal implants, is currently constrained by the spatial resolution of electrical stimulation. Optogenetics has improved the spatial control of neurons in vivo but lacks the fast-temporal dynamics required for auditory and retinal signalling. The objective of this study is to demonstrate that combining optical and electrical stimulation in vitro could address some of the limitations associated with each of the stimulus modes when used independently. APPROACH: The response of murine auditory neurons expressing ChR2-H134 to combined optical and electrical stimulation was characterised using whole cell patch clamp electrophysiology. MAIN RESULTS: Optogenetic costimulation produces a three-fold increase in peak firing rate compared to optical stimulation alone and allows spikes to be evoked by combined subthreshold optical and electrical inputs. Subthreshold optical depolarisation also facilitated spiking in auditory neurons for periods of up to 30 ms without evidence of wide-scale Na+ inactivation. Significance These findings may contribute to the development of spatially and temporally selective optogenetic-based neuroprosthetics and complement recent developments in "fast opsins".
Combining cell-based therapies and neural prostheses to promote neural survival
(Springer, 2011-10) Wise, Andrew; Fallon, James; Neil, Alison; Pettingill, Lisa; Geaney, Marilyn; Skinner, Stephen; Shepherd, Robert
Cochlear implants provide partial restoration of hearing for profoundly deaf patients by electrically stimulating spiral ganglion neurons (SGNs); however, these neurons gradually degenerate following the onset of deafness. Although the exogenous application of neurotrophins (NTs) can prevent SGN loss, current techniques to administer NTs for long periods of time have limited clinical applicability. We have used encapsulated choroid plexus cells (NTCells; Living Cell Technologies, Auckland, New Zealand) to provide NTs in a clinically viable manner that can be combined with a cochlear implant. Neonatal catswere deafened and unilaterally implanted with NTCells and a cochlear implant. Animals received chronic electrical stimulation (ES) alone, NTs alone, or combined NTs and ES (ES + NT) for a period of as much as 8 months. The opposite ear served as a deafened unimplanted control. Chronic ES alone did not result in increased survival of SGNs or their peripheral processes. NT treatment alone resulted in greater SGN survival restricted to the upper basal cochlear region and an increased density of SGN peripheral processes. Importantly, chronic ES in combination with NTs provided significant SGN survival throughout a wider extent of the cochlea, in addition to an increased peripheral process density. Re-sprouting peripheral processes were observed in the scala media and scala tympani, raising the possibility of direct contact between peripheral processes and a cochlear implant electrode array. We conclude that cell-based therapy is clinically viable and effective in promoting SGN survival for extended durations of cochlear implant use. These findings have important implications for the safe delivery of therapeutic drugs to the cochlea.
Comparing Perilymph Proteomes Across Species
(Wiley, 2018-01) Palmer, Jonathon; Lord, Megan; Pinyon, Jeremy; Wise, Andrew; Lovell, Nigel; Carter, Paul; Enke, Ya Lang; Housley, Gary; Green, Rylie
OBJECTIVES/HYPOTHESIS: Biological components of perilymph affect the electrical performance of cochlear implants. Understanding the perilymph composition of common animal models will improve the understanding of this impact and improve the interpretation of results from animal studies and how it relates to humans. STUDY DESIGN: Analysis and comparison of the proteomes of human, guinea pig, and cat perilymph. METHODS: Multiple perilymph samples from both guinea pigs and cats were analysed via liquid chromatography with tandem mass spectrometry. Proteins were identified using the Mascot database. Human data were obtained from a published dataset. Proteins identified were refined to form a proteome for each species. RESULTS: Over 200 different proteins were found per species. There were 81, 39, and 64 proteins in the final human, guinea pig, and cat proteomes, respectively. Twenty-one proteins were common to all three species. Fifty-two percent of the cat proteome was found in the human proteome, and 31% of the guinea pig was common to human. The cat proteome had similar complexity to the human proteome in three protein classes, whereas the guinea pig had a similar complexity in two. The presence of albumin was significantly higher in human perilymph than in the other two species. Immunoglobulins were more abundant in the human than in the cat proteome. CONCLUSIONS: Perilymph proteomes were compared across three species. The degree of crossover of proteins of both guinea pig and cat with human indicate that these animals suitable models for the human cochlea, albeit the cat perilymph is a closer match. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E47-E52, 2018.
Drug delivery to the inner ear
(IOP Science, 2012-12) Wise, Andrew; Gillespie, Lisa
Bionic devices electrically activate neural populations to partially restore lost function. Of fundamental importance is the functional integrity of the targeted neurons. However, in many conditions the ongoing pathology can lead to continued neural degeneration and death that may compromise the effectiveness of the device and limit future strategies to improve performance. The use of drugs that can prevent nerve cell degeneration and promote their regeneration may improve clinical outcomes. In this paper we focus on strategies of delivering neuroprotective drugs to the auditory system in a way that is safe and clinically relevant for use in combination with a cochlear implant. The aim of this approach is to prevent neural degeneration and promote nerve regrowth in order to improve outcomes for cochlear implant recipients using techniques that can be translated to the clinic.
The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes
(John Wiley & Sons Ltd, 2017-01) Burroughs, Amelia; Wise, Andrew; Xiao, Jianqiang; Houghton, Conor; Tang, Tianyu; Suh, Colleen; Lang, Eric J; Apps, Richard; Cerminara, Nadia L
Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake cats. In addition, complex spikes with a greater number of spikelets were associated with a subsequent reduction in simple spike firing rate. We therefore suggest that one important function of spikelets is the modulation of Purkinje cell simple spike firing frequency, which has implications for controlling cerebellar cortical output and motor learning.
The effect of deafness duration on neurotrophin gene therapy for spiral ganglion neuron protection
(Elsevier, 2011-08) Wise, Andrew; Tu, Tian; Atkinson, Patrick; Flynn, Brianna; Sgro, Beatrice; Hume, Cliff; O'Leary, Stephen; Shepherd, Robert; Richardson, Rachael
A cochlear implant can restore hearing function by electrically exciting spiral ganglion neurons (SGNs) in the deaf cochlea. However, following deafness SGNs undergo progressive degeneration ultimately leading to their death. One significant cause of SGN degeneration is the loss of neurotrophic support that is normally provided by cells within the organ of Corti (OC). The administration of exogenous neurotrophins (NTs) can protect SGNs from degeneration but the effects are short-lived once the source of NTs has been exhausted. NT gene therapy, whereby cells within the cochlea are transfected with genes enabling them to produce NTs, is one strategy for providing a cellular source of NTs that may provide long-term support for SGNs. As the SGNs normally innervate sensory cells within the OC, targeting residual OC cells for gene therapy in the deaf cochlea may provide a source of NTs for SGN protection and targeted regrowth of their peripheral fibers. However, the continual degeneration of the OC over extended periods of deafness may deplete the cellular targets for NT gene therapy and hence limit the effectiveness of this method in preventing SGN loss. This study examined the effects of deafness duration on the efficacy of NT gene therapy in preventing SGN loss in guinea pigs that were systemically deafened with aminoglycosides. Adenoviral vectors containing green fluorescent protein (GFP) with or without genes for Brain Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT3) were injected into the scala media (SM) compartment of cochleae that had been deafened for one, four or eight weeks prior to the viral injection. The results showed that viral transfection of cells within the SM was still possible even after severe degeneration of the OC. Supporting cells (pillar and Deiters' cells), cells within the stria vascularis, the spiral ligament, endosteal cells lining the scala compartments and interdental cells in the spiral limbus were transfected. However, the level of transfection was remarkably lower following longer durations of deafness. There was a significant increase in SGN survival in the entire basal turn for cochleae that received NT gene therapy compared to the untreated contralateral control cochleae for the one week deaf group. In the four week deaf group significant SGN survival was observed in the lower basal turn only. There was no increase in SGN survival for the eight week deaf group in any cochlear region. These findings indicated that the efficacy of NT gene therapy diminished with increasing durations of deafness leading to reduced benefits in terms of SGN protection. Clinically, there remains a window of opportunity in which NT gene therapy can provide ongoing trophic support for SGNs.
Effects of age on the preservation of residual hearing with cochlear implants
(2013) Wise, Andrew; Irving, Sam; Shepherd, Robert; Fallon, James
Chronic cochlear implant (CI) use results in a significant loss of residual acoustic hearing in some, but not all, animals. The loss occurs more rapidly in animals deafened as adults than those deafened as neonates.
Effects of deafness and cochlear implant use on temporal response characteristics in cat primary auditory cortex.
(Elsevier, 2014-09) Fallon, James; Shepherd, Robert; Nayagam, David; Wise, Andrew; Heffer, Leon; Landry, Thomas; Irvine, Dexter
We have previously shown that neonatal deafness of 7-13 months duration leads to loss of cochleotopy in the primary auditory cortex (AI) that can be reversed by cochlear implant use. Here we describe the effects of a similar duration of deafness and cochlear implant use on temporal processing. Specifically, we compared the temporal resolution of neurons in AI of young adult normal-hearing cats that were acutely deafened and implanted immediately prior to recording with that in three groups of neonatally deafened cats. One group of neonatally deafened cats received no chronic stimulation. The other two groups received up to 8 months of either low- or high-rate (50 or 500 pulses per second per electrode, respectively) stimulation from a clinical cochlear implant, initiated at 10 weeks of age. Deafness of 7-13 months duration had no effect on the duration of post-onset response suppression, latency, latency jitter, or the stimulus repetition rate at which units responded maximally (best repetition rate), but resulted in a statistically significant reduction in the ability of units to respond to every stimulus in a train (maximum following rate). None of the temporal response characteristics of the low-rate group differed from those in acutely deafened controls. In contrast, high-rate stimulation had diverse effects: it resulted in decreased suppression duration, longer latency and greater jitter relative to all other groups, and an increase in best repetition rate and cut-off rate relative to acutely deafened controls. The minimal effects of moderate-duration deafness on temporal processing in the present study are in contrast to its previously-reported pronounced effects on cochleotopy. Much longer periods of deafness have been reported to result in significant changes in temporal processing, in accord with the fact that duration of deafness is a major factor influencing outcome in human cochlear implantees.
Electro-acoustic stimulation: now and into the future
(Hindawi Publishing Corporation, 2014) Irving, Samuel; Gillespie, Lisa; Richardson, Rachael; Rowe, David; Fallon, James; Wise, Andrew
Cochlear implants have provided hearing to hundreds of thousands of profoundly deaf people around the world. Recently, the eligibility criteria for cochlear implantation have been relaxed to include individuals who have some useful residual hearing. These recipients receive inputs from both electric and acoustic stimulation (EAS). Implant recipients who can combine these hearing modalities demonstrate pronounced benefit in speech perception, listening in background noise and music appreciation over implant recipients that rely on electrical stimulation alone. The mechanisms bestowing this benefit are unknown, but it is likely that interaction of the electric and acoustic signals in the auditory pathway play a role. Protection of residual hearing both during and following cochlear implantation is critical for EAS. A number of surgical refinements have been implemented to protect residual hearing, and the development of hearing-protective drug and gene therapies is promising for EAS recipients. This review outlines the current field of EAS, with a focus on interactions that are observed between these modalities in animal models. It also outlines current trends in EAS surgery and gives an overview of the drug and gene therapies that are clinically translatable and may one day provide protection of residual hearing for cochlear implant recipients.
Electrophysiological channel interactions using focused multipolar stimulation for cochlear implants
(IOP Publishing Ltd, 2015-09) George, Shefin; Shivdasani, Mohit; Wise, Andrew; Shepherd, Robert; Fallon, James
Objective. Speech intelligibility with existing multichannel cochlear implants (CIs) is thought to be limited by poor spatial selectivity and interactions between CI channels caused by overlapping activation with monopolar (MP) stimulation. Our previous studies have shown that focused multipolar (FMP) and tripolar (TP) stimulation produce more restricted neural activation in the inferior colliculus (IC), compared to MP stimulation. Approach. This study explored interactions in the IC produced by simultaneous stimulation of two CI channels. We recorded multi-unit neural activity in the IC of anaesthetized cats with normal and severely degenerated spiral ganglion neuron populations in response to FMP, TP and MP stimulation from a 14 channel CI. Stimuli were applied to a 'fixed' CI channel, chosen toward the middle of the cochlear electrode array, and the effects of simultaneously stimulating a more apical 'test' CI channel were measured as a function of spatial separation between the two stimulation channels and stimulus level of the fixed channel. Channel interactions were quantified by changes in neural responses and IC threshold (i.e., threshold shift) elicited by simultaneous stimulation of two CI channels, compared to stimulation of the test channel alone. Main results. Channel interactions were significantly lower for FMP and TP than for MP stimulation (p < 0.001), whereas no significant difference was observed between FMP and TP stimulation. With MP stimulation, threshold shifts increased with decreased inter-electrode spacing and increased stimulus levels of the fixed channel. For FMP and TP stimulation, channel interactions were found to be similar for different inter-electrode spacing and stimulus levels of the fixed channel. Significance. The present study demonstrates how the degree of channel interactions in a CI can be controlled using stimulation configurations such as FMP and TP; such knowledge is essential in enhancing CI function in complex acoustic environments.
Engineering Biocoatings To Prolong Drug Release from Supraparticles
(American Chemical Society, 2019-08) Ma, Yutian; Cortez-Jugo, Christina; Li, Jianhua; Lin, Zhixing; Richardson, Rachael; Han, Yiyuan; Zhou, Jiajing; Björnmalm, Mattias; Feeney, Orlagh; Zhong, Qi-Zhi; Porter, Christopher; Wise, Andrew; Caruso, Frank
Supraparticles (SPs) assembled from smaller colloidal nanoparticles can serve as depots of therapeutic compounds and are of interest for long-term, sustained drug release in biomedical applications. However, a key challenge to achieving temporal control of drug release from SPs is the occurrence of an initial rapid release of the loaded drug (i.e., "burst" release) that limits sustained release and potentially causes burst release-associated drug toxicity. Herein, a biocoating strategy is presented for silica-SPs (Si-SPs) to reduce the extent of burst release of the loaded model protein lysozyme. Specifically, Si-SPs were coated with a fibrin film, formed by enzymatic conversion of fibrinogen into fibrin. The fibrin-coated Si-SPs, (F)Si-SPs, which could be loaded with 7.9 +/- 0.9 mug of lysozyme per SP, released >60% of cargo protein over a considerably longer period of time of >20 days when compared with the uncoated Si-SPs that released the same amount of the cargo protein, however, within the first 3 days. Neurotrophins that support the survival and differentiation of neurons could also be loaded at approximately 7.3 mug per SP, with fibrin coating also delaying neurotrophin release (only 10% of cargo released over 21 days compared with 60% from Si-SPs). In addition, the effects of incorporating a hydrogel-based system for surgical delivery and the opportunity to control drug release kinetics were investigated-an alginate-based hydrogel scaffold was used to encapsulate (F)Si-SPs. The introduction of the hydrogel further extended the initial release of the encapsulated lysozyme to approximately 40 days (for the same amount of cargo released). The results demonstrate the increasing versatility of the SP drug delivery platform, combining large loading capacity with sustained drug release, that is tailorable using different modes of controlled delivery approaches.
Enhanced auditory neuron survival following cell- based BDNF treatment in the deaf guinea pig
(PLOS, 2011-04-05) Pettingill, Lisa; Wise, Andrew; Geaney, Marilyn; Shepherd, Robert
Exogenous neurotrophin delivery to the deaf cochlea can prevent deafness-induced auditory neuron degeneration, however, we have previously reported that these survival effects are rapidly lost if the treatment stops. In addition, there are concerns that current experimental techniques are not safe enough to be used clinically. Therefore, for such treatments to be clinically transferable, methods of neurotrophin treatment that are safe, biocompatible and can support long-term auditory neuron survival are necessary. Cell transplantation and gene transfer, combined with encapsulation technologies, have the potential to address these issues. This study investigated the survival-promoting effects of encapsulated BDNF over-expressing Schwann cells on auditory neurons in the deaf guinea pig. In comparison to control (empty) capsules, there was significantly greater auditory neuron survival following the cell-based BDNF treatment. Concurrent use of a cochlear implant is expected to result in even greater auditory neuron survival, and provide a clinically relevant method to support auditory neuron survival that may lead to improved speech perception and language outcomes for cochlear implant patients.
Evaluation of focused multipolar stimulation for cochlear implants in acutely deafened cats
(IOP Publishing, 2014-11) George, Shefin; Wise, Andrew; Shivdasani, Mohit; Shepherd, Robert; Fallon, James
OBJECTIVE: The conductive nature of the fluids and tissues of the cochlea can lead to broad activation of spiral ganglion neurons using contemporary cochlear implant stimulation configurations such as monopolar (MP) stimulation. The relatively poor spatial selectivity is thought to limit implant performance, particularly in noisy environments. Several current focusing techniques have been proposed to reduce the spread of activation with the aim towards achieving improved clinical performance. APPROACH: The present research evaluated the efficacy of focused multipolar (FMP) stimulation, a relatively new focusing technique in the cochlea, and compared its efficacy to both MP stimulation and tripolar (TP) stimulation. The spread of neural activity across the inferior colliculus (IC), measured by recording the spatial tuning curve, was used as a measure of spatial selectivity. Adult cats (n = 6) were acutely deafened and implanted with an intracochlear electrode array before multi-unit responses were recorded across the cochleotopic gradient of the contralateral IC. Recordings were made in response to acoustic and electrical stimulation using the MP, TP and FMP configurations. MAIN RESULTS: FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation. However, thresholds were significantly higher (p < 0.001) for FMP and TP stimulation compared to MP stimulation. There were no differences found in spatial selectivity and threshold between FMP and TP stimulation. SIGNIFICANCE: The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance. However, further research will be required to demonstrate the efficacy of these modes of stimulation after longer durations of deafness.
Evaluation of focused multipolar stimulation for cochlear implants in long-term deafened cats
(IOP Publishing, 2015-06) George, Shefin; Wise, Andrew; Fallon, James; Shepherd, Robert
Objective: Focused multipolar (FMP) stimulation has been shown to produce restricted neural activation using intracochlear stimulation in animals with a normal population of spiral ganglion neurons (SGNs). However, in a clinical setting, the widespread loss of SGNs and peripheral fibers following deafness is expected to influence the effectiveness of FMP. Approach: We compared the efficacy of FMP stimulation to both monopolar (MP) and tripolar (TP) stimulation in long-term deafened cat cochleae (n=8). Unlike our previous study, these cochleae contained <10% of the normal SGN population adjacent to the electrode array. We also evaluated the effect of electrode position on stimulation modes by using either modiolar facing or lateral wall facing half-band electrodes. The spread of neural activity across the inferior colliculus, a major nucleus within the central auditory pathway, was used as a measure of spatial selectivity. Main results: In cochleae with significant SGN degeneration, we observed that FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation (p<0.001). However, thresholds were significantly higher for FMP and TP stimulation compared to MP stimulation (p<0.001). No difference between FMP and TP stimulation was found in any measures. The high threshold levels for FMP stimulation was significantly reduced without compromising spatial selectivity by varying the degree of current focusing (referred as “partial-FMP” stimulation). Spatial selectivity of all stimulation modes was unaffected by the electrode position. Finally, spatial selectivity in long-term deafened cochleae was significantly less than that of cochleae with normal SGN population (George et al., 2014). Significance: The present results indicate that the greater spatial selectivity of FMP and TP stimulation over MP stimulation is maintained in cochleae with significant neural degeneration and is not adversely affected by electrode position. The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance.
Evaluation of focused multipolar stimulation for cochlear implants: a preclinical safety study
(IOP Publishing Ltd, 2017-06) Shepherd, Robert; Wise, Andrew; Enke, Ya Lang; Carter, Paul; Fallon, James
OBJECTIVE: Cochlear implants (CIs) have a limited number of independent stimulation channels due to the highly conductive nature of the fluid-filled cochlea. Attempts to develop highly focused stimulation to improve speech perception in CI users includes the use of simultaneous stimulation via multiple current sources. Focused multipolar (FMP) stimulation is an example of this approach and has been shown to reduce interaction between stimulating channels. However, compared with conventional biphasic current pulses generated from a single current source, FMP is a complex stimulus that includes extended periods of stimulation before charge recovery is achieved, raising questions on whether chronic stimulation with this strategy is safe. The present study evaluated the long-term safety of intracochlear stimulation using FMP in a preclinical animal model of profound deafness. APPROACH: Six cats were bilaterally implanted with scala tympani electrode arrays two months after deafening, and received continuous unilateral FMP stimulation at levels that evoked a behavioural response for periods of up to 182 d. Electrode impedance, electrically-evoked compound action potentials (ECAPs) and auditory brainstem responses (EABRs) were monitored periodically over the course of the stimulation program from both the stimulated and contralateral control cochleae. On completion of the stimulation program cochleae were examined histologically and the electrode arrays were evaluated for evidence of platinum (Pt) corrosion. MAIN RESULTS: There was no significant difference in electrode impedance between control and chronically stimulated electrodes following long-term FMP stimulation. Moreover, there was no significant difference between ECAP and EABR thresholds evoked from control or stimulated cochleae at either the onset of stimulation or at completion of the stimulation program. Chronic FMP stimulation had no effect on spiral ganglion neuron (SGN) survival when compared with unstimulated control cochleae. Long-term implantation typically evoked a mild foreign body reaction proximal to the electrode array; however stimulated cochleae exhibited a small but statistically significant increase in the tissue response. Finally, there was no evidence of Pt corrosion following long-term FMP stimulation; stimulated electrodes exhibited the same surface features as the unstimulated control electrodes. SIGNIFICANCE: Chronic intracochlear FMP stimulation at levels used in the present study did not adversely affect electrically-evoked neural thresholds or SGN survival but evoked a small, benign increase in inflammatory response compared to control ears. Moreover chronic FMP stimulation does not affect the surface of Pt electrodes at suprathreshold stimulus levels. These findings support the safe clinical application of an FMP stimulation strategy.

Browsing by Author "Wise, Andrew"

Results Per Page

Sort Options