Browsing by Author "Millard, Rodney"

Now showing 1 - 9 of 9
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    An automated system for rapid evaluation of high-density electrode arrays in neural prostheses
    (Institute of Physics, 2011-06) John, Sam; Shivdasani, Mohit; Leuenberger, James; Fallon, James; Shepherd, Robert; Millard, Rodney; Rathbone, Graeme; Williams, Chris
    The success of high density electrode arrays for use in neural prostheses depends on efficient impedance monitoring and fault detection. Conventional methods of impedance testing and fault detection are time consuming and are not always suited for in-vivo assessment of high density electrode arrays. Additionally the ability to evaluate impedances and faults such as open and short circuits both, in-vitro and in-vivo are important to ensure safe and effective stimulation. In the present work we describe an automated system for the rapid evaluation of high density electrode arrays. The system uses a current pulse similar to that used to stimulate neural tissue and measures the voltage across the electrode in order to calculate the impedance. The switching of the system was validated by emulating a high density electrode array using light emitting diodes and a resistor- capacitor network. The system was tested in-vitro and in-vivo using a range of commercially available and in-house developed electrode arrays. The system accurately identified faults on an 84 electrode array in less than 20 seconds and reliably measured impedances up to 110 kn using a 200µA, 250 µs per phase current pulse. This system has direct application for screening high density electrode arrays in both a clinical and experimental setting.
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    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.
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    Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells
    (Hindawi Publishing Corporation, 2016) Hernandez, Damian; Millard, Rodney; Sivakumaran, Priyadharshini; Wong, Raymond; Crombi, Duncan; Hewitt, Alex; Liang, Helena; Hung, Sandy; Pebay, Alice; Shepherd, Robert; Dusting, Gregory; Lim, Shiang
    Background.Human induced pluripotent stemcells (iPSCs) are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes. Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs) for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days. Results. In iPS(Foreskin)-2 cell line, brief electrical stimulation at 65mV/mm or 200mV/mm for 5 min significantly increased the percentage of beating EBs present by day 14 after plating. Acute electrical stimulation also significantly increased the cardiac gene expression of ACTC1, TNNT2, MYH7, and MYL7. However, the cardiogenic effect of electrical stimulation was not reproducible in another iPS cell line,CERA007c6. Beating EBs from control and electrically stimulated groups expressed various cardiac-specific transcription factors and contractile muscle markers. Beating EBs were also shown to cycle calcium and were responsive to the chronotropic agents, isoproterenol and carbamylcholine, in a concentration-dependent manner. Conclusions. Our results demonstrate that brief electrical stimulation can promote cardiac differentiation of human iPS cells.The cardiogenic effect of brief electrical stimulation is dependent on the cell line used.
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    A Flexible Wireless System for Preclinical Evaluation of Retinal Prosthesis
    (MYU KK, 2018-01) Thien, Patrick; Millard, Rodney; Epp, Stephanie; Nayagam, David
    In this paper, we present a novel stimulation controller and monitoring system for evaluating the safety and efficacy of implantable neuroprosthetic devices in a preclinical setting. It features a programmable controller designed to be worn in a custom backpack by freely moving feline subjects. A custom controller powered two, modified, 22-channel clinical stimulators simultaneously. The controller and stimulators together weighed 140 g and measured 85 × 70 × 35 mm3. Power was supplied from a 3350 mAh lithium-ion battery. A Bluetooth-enabled laptop-PC base station managed up to six systems and allowed the remote adjustment of the stimulation amplitude and automated collection of stimulator telemetry data. The initial application was for the chronic safety testing of a 44-channel retinal prosthesis. Thirteen feline subjects were implanted with a suprachoroidal electrode array, which was then stimulated or monitored continuously for an average of 54.5 d. Batteries were changed twice weekly and electrode impedances were recorded hourly. This allowed broken electrodes and other issues to be quickly identified and addressed. The ability to remotely control the stimulation amplitude minimised the amount of subject handling that was required, likely reducing subject stress. Existing preclinical evaluation systems are either designed for short-term experiments and have many features but limited battery life, or for long-term static stimulation and are long-lived, but with restricted stimulation parameters and channel counts. Here, we have described a system designed to improve the chronic safety testing of electrode arrays. While it was used here with a suprachoroidal retinal implant, it could be readily adapted for other preclinical models requiring continuous, deterministic stimulation over a prolonged period.
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    Impedance changes in chronically implanted and stimulated cochlear implant electrodes.
    (WS Maney & Son, 2014) Newbold, Carrie; Mergen, Silvana; Richardson, Rachael; Seligman, Peter; Millard, Rodney; Cowan, Robert; Shepherd, Robert
    OBJECTIVES: Electrode impedance increases following implantation and undergoes transitory reduction with onset of electrical stimulation. The studies in this paper measured the changes in access resistance and polarization impedance in vivo before and following electrical stimulation, and recorded the time course of these changes. DESIGN: Impedance measures recorded in (a) four cats following 6 months of cochlear implant use, and (b) three cochlear implant recipients with 1.5-5 years cochlear implant experience. RESULTS: Both the experimental and clinical data exhibited a reduction in electrode impedance, 20 and 5% respectively, within 15-30 minutes of stimulation onset. The majority of these changes occurred through reduction in polarization impedance. Cessation of stimulation was followed by an equivalent rise in impedance measures within 6-12 hours. CONCLUSIONS: Stimulus-induced reductions in impedance exhibit a rapid onset and are evident in both chronic in vivo models tested, even several years after implantation. Given the impedance changes were dominated by the polarization component, these findings suggest that the electrical stimulation altered the electrode surface rather than the bulk tissue and fluid in the cochlea.
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    Influence of continuous electrical stimulation on development of human cardiomyocytes from induced pluripotent stem cells
    (Conditioning Medicine, 2018-11) Hernandez, Damian; Millard, Rodney; Sivakumaran, Priyadharshini; Kong, Anne; Mitchell, Geraldine; Pebay, Alice; Shepherd, Robert; Dusting, Gregory; Lim, Shiang
    Regeneration of cardiac tissue remains an ideal approach to restore cardiac function after myocardial infarction. The ability of human induced pluripotent stem cells (iPSCs) to differentiate into bona fide cardiomyocytes also provides a platform for cardiac disease modeling, drug discovery and pharmacological safety testing of new drugs. One of the major limitations for the use of cardiomyocytes derived from iPSCs is that they resemble fetal cardiomyocytes and are immature compared to adult cardiomyocytes. Considering that the developing heart grows in an electric field, we investigated whether electrical stimulation can promote maturation of cardiomyocytes derived from human iPSCs. Two-dimensional cultures of immature cardiomyocytes at day 22 post-differentiation were subjected to continuous electrical stimulation at 200 mV/mm for 7 days using a custom-made electrical stimulator. This long-term electrical stimulation significantly increased the percentage of cardiomyocytes with organized sarcomeres and promoted alignment of cardiomyocytes parallel to the electric field. Electrical stimulation also decreased the circularity index of cardiomyocytes suggesting a more rod-like morphology. In conclusion, long-term continuous electrical stimulation promotes maturation of cardiomyocytes derived from human iPSCs. Mature cardiomyocytes can better recapitulate the pathophysiological conditions of the human heart for more accurate disease modeling and drug testing. Mature cardiomyocytes can also provide a substrate for cardiac regeneration and repair by tissue engineering in the future.
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    A partial hearing animal model for chronic electro-acoustic stimulation
    (IOP Publishing, 2014-06) Irving, Samuel; Wise, Andrew; Millard, Rodney; Shepherd, Robert; Fallon, James
    OBJECTIVE: Cochlear implants (CIs) have provided some auditory function to hundreds of thousands of people around the world. Although traditionally carried out only in profoundly deaf patients, the eligibility criteria for implantation have recently been relaxed to include many partially-deaf patients with useful levels of hearing. These patients receive both electrical stimulation from their implant and acoustic stimulation via their residual hearing (electro-acoustic stimulation; EAS) and perform very well. It is unclear how EAS improves speech perception over electrical stimulation alone, and little evidence exists about the nature of the interactions between electric and acoustic stimuli. Furthermore, clinical results suggest that some patients that undergo cochlear implantation lose some, if not all, of their residual hearing, reducing the advantages of EAS over electrical stimulation alone. A reliable animal model with clinically-relevant partial deafness combined with clinical CIs is important to enable these issues to be studied. This paper outlines such a model that has been successfully used in our laboratory. APPROACH: This paper outlines a battery of techniques used in our laboratory to generate, validate and examine an animal model of partial deafness and chronic CI use. MAIN RESULTS: Ototoxic deafening produced bilaterally symmetrical hearing thresholds in neonatal and adult animals. Electrical activation of the auditory system was confirmed, and all animals were chronically stimulated via adapted clinical CIs. Acoustic compound action potentials (CAPs) were obtained from partially-hearing cochleae, using the CI amplifier. Immunohistochemical analysis allows the effects of deafness and electrical stimulation on cell survival to be studied. SIGNIFICANCE: This animal model has applications in EAS research, including investigating the functional interactions between electric and acoustic stimulation, and the development of techniques to maintain residual hearing following cochlear implantation. The ability to record CAPs via the CI has clinical direct relevance for obtaining objective measures of residual hearing.
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    Promoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodes
    (Wiley Periodicals, 2009-10) Evans, Alison; Thompson, Brianna; Wallace, Gordon; Millard, Rodney; O'Leary, Stephen; Clark, Graeme; Shepherd, Robert; Richardson, Rachael
    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 seven days. A three-day SGN explant assay found 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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    Ring and peg electrodes for minimally-Invasive and long-term sub-scalp EEG recordings
    (Elsevier, Ltd., 2017-06) Benovitski, Yuri; Lai, Alan; McGowan, Ceara; Burns, Owen; Maxim, Vanessa; Nayagam, David; Millard, Rodney; Rathbone, Graeme; le Chevoir, M.A.; Williams, R.A.; Grayden, David; May, C.N.; Murphy, M.; D'Souza, Wendyl; Cook, Mark; Williams, Chris
    OBJECTIVE: Minimally-invasive approaches are needed for long-term reliable Electroencephalography (EEG) recordings to assist with epilepsy diagnosis, investigation and more naturalistic monitoring. This study compared three methods for long-term implantation of sub-scalp EEG electrodes. METHODS: Three types of electrodes (disk, ring, and peg) were fabricated from biocompatible materials and implanted under the scalp in five ambulatory ewes for 3months. Disk electrodes were inserted into sub-pericranial pockets. Ring electrodes were tunneled under the scalp. Peg electrodes were inserted into the skull, close to the dura. EEG was continuously monitored wirelessly. High resolution CT imaging, histopathology, and impedance measurements were used to assess the status of the electrodes at the end of the study. RESULTS: EEG amplitude was larger in the peg compared with the disk and ring electrodes (p<0.05). Similarly, chewing artifacts were lower in the peg electrodes (p<0.05). Electrode impedance increased after long-term implantation particularly for those within the bone (p<0.01). Micro-CT scans indicated that all electrodes stayed within the sub-scalp layers. All pegs remained within the burr holes as implanted with no evidence of extrusion. Eight of 10 disks partially eroded into the bone by 1.0mm from the surface of the skull. The ring arrays remained within the sub-scalp layers close to implantation site. Histology revealed that the electrodes were encapsulated in a thin fibrous tissue adjacent to the pericranium. Overlying this was a loose connective layer and scalp. Erosion into the bone occurred under the rim of the sub-pericranial disk electrodes. CONCLUSIONS: The results indicate that the peg electrodes provided high quality EEG, mechanical stability, and lower chewing artifact. Whereas, ring electrode arrays tunneled under the scalp enable minimal surgical techniques to be used for implantation and removal.