832 research outputs found

    Dampening Spontaneous Activity Improves the Light Sensitivity and Spatial Acuity of Optogenetic Retinal Prosthetic Responses

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    Retinitis pigmentosa is a progressive retinal dystrophy that causes irreversible visual impairment and blindness. Retinal prostheses currently represent the only clinically available vision-restoring treatment, but the quality of vision returned remains poor. Recently, it has been suggested that the pathological spontaneous hyperactivity present in dystrophic retinas may contribute to the poor quality of vision returned by retinal prosthetics by reducing the signal-to-noise ratio of prosthetic responses. Here, we investigated to what extent blocking this hyperactivity can improve optogenetic retinal prosthetic responses. We recorded activity from channelrhodopsin-expressing retinal ganglion cells in retinal wholemounts in a mouse model of retinitis pigmentosa. Sophisticated stimuli, inspired by those used in clinical visual assessment, were used to assess light sensitivity, contrast sensitivity and spatial acuity of optogenetic responses; in all cases these were improved after blocking spontaneous hyperactivity using meclofenamic acid, a gap junction blocker. Our results suggest that this approach significantly improves the quality of vision returned by retinal prosthetics, paving the way to novel clinical applications. Moreover, the improvements in sensitivity achieved by blocking spontaneous hyperactivity may extend the dynamic range of optogenetic retinal prostheses, allowing them to be used at lower light intensities such as those encountered in everyday life

    Implantable CMOS Biomedical Devices

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    The results of recent research on our implantable CMOS biomedical devices are reviewed. Topics include retinal prosthesis devices and deep-brain implantation devices for small animals. Fundamental device structures and characteristics as well as in vivo experiments are presented

    Towards Immersive Virtual Reality Simulations of Bionic Vision

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    Bionic vision is a rapidly advancing field aimed at developing visual neuroprostheses ('bionic eyes') to restore useful vision to people who are blind. However, a major outstanding challenge is predicting what people 'see' when they use their devices. The limited field of view of current devices necessitates head movements to scan the scene, which is difficult to simulate on a computer screen. In addition, many computational models of bionic vision lack biological realism. To address these challenges, we propose to embed biologically realistic models of simulated prosthetic vision (SPV) in immersive virtual reality (VR) so that sighted subjects can act as 'virtual patients' in real-world tasks.Comment: 3 pages, 2 figures, to be presented at Augmented Human

    Towards clinical trials of a novel Bionic Eye: Building evidence of safety and efficacy

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    In the quest for therapeutic solutions for the visually impaired, electrical stimulation of the retina is, and has been, the focus of intense research. Some of these efforts have led to the development of the Phoenix99 Bionic Eye, a device which combines promising technological features with novel stimulation strategies. For medical devices, considerable challenges must be overcome before they’re allowed to be trialled in their target population. The requirements for a study to be performed include the demonstration of a positive risk-benefit ratio of the research. The present dissertation is an attempt to address how pre-clinical trials in animals can be used to understand and minimise risks. A positive risk-benefit ratio means that the potential benefits of the research outweigh the risks of the intervention. In the case of retinal prostheses, the risks include the surgical intervention, the immune response to the device, the safety of the electrical stimuli, and the effects of device ageing. In this work, successful demonstration of the surgical safety and biocompatibility of passive Phoenix99 devices during long-term implantation in sheep called for the evaluation of the chronic effects of the novel stimulation paradigms it can deliver. As preparation for this study, the techniques used to evaluate the safety and efficacy of the stimuli in animals were refined. A systematic approach to minimise the impact of anaesthesia on the experimental results is presented, as well as a novel in vivo retinal recording technique. To maximise the clinical relevance of all animal trials, a computer model for the prediction of thresholds was developed. Finally, in vitro device ageing was performed to deepen our understanding of the design’s potential for long-term implantation. Protocols for a long-term device safety study in sheep and for an acute human trial are also presented, thus taking concrete and sensible steps towards the first clinical use of the Phoenix99 Bionic Eye

    A review of in vivo animal studies in retinal prosthesis research

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    Background: The development of a functional retinal prosthesis for acquired blindness is a great challenge. Rapid progress in the field over the last 15years would not have been possible without extensive animal experimentation pertaining to device design and fabrication, biocompatibility, stimulation parameters and functional responses. This paper presents an overview of in vivo animal research related to retinal prosthetics, and aims to summarize the relevant studies. Methods: A Pubmed search of the English language literature was performed. The key search terms were: retinal implant, retinal prosthesis, artificial vision, rat, rabbit, cat, dog, sheep, pig, minipig. In addition a manual search was performed based on references quoted in the articles retrieved through Pubmed. Results: We identified 50 articles relevant to in vivo animal experimentation directly related to the development of a retinal implant. The highest number of publications related to the cat (n = 18). Conclusion: The contribution of animal models to the development of retinal prosthetic devices has been enormous, and has led to human feasibility studies. Grey areas remain regarding long-term tissue-implant interactions, biomaterials, prosthesis design and neural adaptation. Animals will continue to play a key role in this rapidly evolving fiel

    Non-Penetrating Microelectrode Interfaces for Cortical Neuroprosthetic Applications with a Focus on Sensory Encoding: Feasibility and Chronic Performance in Striate Cortex

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    abstract: Growing understanding of the neural code and how to speak it has allowed for notable advancements in neural prosthetics. With commercially-available implantable systems with bi- directional neural communication on the horizon, there is an increasing imperative to develop high resolution interfaces that can survive the environment and be well tolerated by the nervous system under chronic use. The sensory encoding aspect optimally interfaces at a scale sufficient to evoke perception but focal in nature to maximize resolution and evoke more complex and nuanced sensations. Microelectrode arrays can maintain high spatial density, operating on the scale of cortical columns, and can be either penetrating or non-penetrating. The non-penetrating subset sits on the tissue surface without puncturing the parenchyma and is known to engender minimal tissue response and less damage than the penetrating counterpart, improving long term viability in vivo. Provided non-penetrating microelectrodes can consistently evoke perception and maintain a localized region of activation, non-penetrating micro-electrodes may provide an ideal platform for a high performing neural prosthesis; this dissertation explores their functional capacity. The scale at which non-penetrating electrode arrays can interface with cortex is evaluated in the context of extracting useful information. Articulate movements were decoded from surface microelectrode electrodes, and additional spatial analysis revealed unique signal content despite dense electrode spacing. With a basis for data extraction established, the focus shifts towards the information encoding half of neural interfaces. Finite element modeling was used to compare tissue recruitment under surface stimulation across electrode scales. Results indicated charge density-based metrics provide a reasonable approximation for current levels required to evoke a visual sensation and showed tissue recruitment increases exponentially with electrode diameter. Micro-scale electrodes (0.1 – 0.3 mm diameter) could sufficiently activate layers II/III in a model tuned to striate cortex while maintaining focal radii of activated tissue. In vivo testing proceeded in a nonhuman primate model. Stimulation consistently evoked visual percepts at safe current thresholds. Tracking perception thresholds across one year reflected stable values within minimal fluctuation. Modulating waveform parameters was found useful in reducing charge requirements to evoke perception. Pulse frequency and phase asymmetry were each used to reduce thresholds, improve charge efficiency, lower charge per phase – charge density metrics associated with tissue damage. No impairments to photic perception were observed during the course of the study, suggesting limited tissue damage from array implantation or electrically induced neurotoxicity. The subject consistently identified stimulation on closely spaced electrodes (2 mm center-to-center) as separate percepts, indicating sub-visual degree discrete resolution may be feasible with this platform. Although continued testing is necessary, preliminary results supports epicortical microelectrode arrays as a stable platform for interfacing with neural tissue and a viable option for bi-directional BCI applications.Dissertation/ThesisDoctoral Dissertation Biomedical Engineering 201

    Characterization of Retinal Ganglion Cell Responses to Electrical Stimulation Using White Noise

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    Retinitis pigmentosa and age-related macular degeneration are two leading causes of degenerative blindness. While there is still not a definitive course of treatment for either of these diseases, there is currently the world over, many different treatment strategies being explored. Of these various strategies, one of the most successful has been retinal implants. Retinal implants are microelectrode or photodiode arrays, that are implanted in the eye of a patient, to electrically stimulate the degenerating retina. Clinical trials have shown that many patients implanted with such a device, are able to regain a certain degree of functional vision. However, while the results of these ongoing clinical trials have been promising, there are still many technical challenges that need to be overcome. One of the biggest challenges facing present implants is the inability to preferentially stimulate different retinal pathways. This is because retinal implants use large-amplitude current or voltage pulses. This in turn leads to the indiscriminate activation of multiple classes of retinal ganglion cells (RGCs), and therefore, an overall reduction in the restored visual acuity. To tackle this issue, we decided to explore a novel stimulus paradigm, in which we present to the retina, a stream of smaller-amplitude subthreshold voltage pulses. By then correlating the retinal spikes to the stimuli preceding them, we calculate temporal input filters for various classes of RGCs, using a technique called spike-triggered averaging (STA). In doing this, we found that ON and OFF RGCs have electrical filters, which are very distinct from each other. This finding creates the possibility for the selective activation of the retina through the use of STA-based waveforms. Finally, using statistical models, we verify how well these temporal filters can predict RGC responses to novel electrical stimuli. In a broad sense, our work represents the successful application of systems engineering tools to retinal prosthetics, in an attempt to answer one of the field’s most difficult questions, namely selective stimulation of the retina
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