Medical Bionics - Theses
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ItemPreclinical investigation of electrical field shaping strategies for retinal prostheses( 2018)Retinal prostheses are a promising technology aimed at restoring vision in people suffering severe retinal degenerative conditions such as retinitis pigmentosa (RP). Present-generation devices achieve this by electrically stimulating the residual neuronal population in the retina following degeneration in order to elicit the perception of light. At present, patients implanted with these devices are able to perceive multiple localised flashes of light, termed phosphenes, which are used to build up an artificial image of the patient's surroundings. However, present-generation retinal implants lack the spatial resolution to provide a suitable replacement for everyday visual tasks. While adequate for rudimentary tasks such as object recognition, motion detection, and pattern recognition, more complex tasks such as reading, facial recognition, and independent navigation are still not possible with modern prosthetic vision devices. Two major issues that affect retinal prostheses are: the large spread of electrical potential in the retina resulting in widespread activation of neurons, undesirable electrical field interaction and the elicitation of large phosphenes that patients find difficult to discriminate between; and that many devices are not able to elicit enough phosphenes to convey complex visual information to patients. The studies presented in this thesis investigated the effectiveness of two multichannel electrical field shaping techniques: focused multipolar (FMP) stimulation and virtual electrode (VE) current steering. These techniques have shown considerable promise in studies conducted with one-dimensional neural prosthetic devices, such as cochlear and deep brain implants, as ways to restrict and `steer' electrical fields. In an effort to find new ways of improving spatial resolution, I have investigated whether these techniques can be adapted for use in a 2D retinal prosthesis. Using a normally-sighted cat model I have demonstrated that FMP stimulation is capable of restricting current spread in two dimensions and eliciting retinal and cortical response patterns with reduced spread compared with responses to the more conventional MP means of stimulation. I have also demonstrated that VE current steering between up to six electrodes can produce cortical activation patterns in predictable locations, with similar spread of neural activation as response patterns to physical electrode stimulation. By varying the proportions of charge applied to steering electrodes, it was also possible to shift the location of cortical activation in two dimensions in a predictable and intuitive fashion. To investigate the effectiveness of these techniques in a model more representative of patients, FMP stimulation and VE current steering were re-evaluated using a cat model of retinal degeneration. Unfortunately, many of the promising results from the normally-sighted cohort were not maintained when applied to degenerate retinae. While FMP stimulation still activated a localised population of retinal neurons, it was not found to elicit cortical response patterns with reduced spread compared to monopolar stimulation. The location of cortical response patterns elicited by VE stimulation were also found to be unpredictable. These results also show evidence of compressed retinotopy and increased spatial selectivity in the degenerate visual system, which significantly altered neural responses to electrical stimulation. These findings demonstrate that FMP stimulation and VE current steering, in their present form, may not be as effective in focusing and steering neural activation when applied to degenerate retinae. These results also provide a greater understanding of the differences between the responses of healthy and degenerate visual systems to electrical stimulation, which I hope will inform the further development and optimisation of these stimulation strategies.
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ItemPrediction and shaping of visual cortex activity for retinal prostheses( 2017)Retinal prostheses are a promising treatment for blindness caused by photoreceptor degeneration. Electrodes implanted in the retina deliver electrical stimuli in the form of current pulses that activate surviving neurons to restore a sense of vision. Clinical trials for such devices have shown that the visual percepts evoked are informative, and can improve the day-to-day life of recipients. However, the spatial resolution of retinal prostheses is a limiting factor, with those who have the highest reported acuity measures still classified as legally blind. Simultaneous stimulation of multiple electrodes is a possible strategy to improve device resolution without increasing the number of physical electrodes. However, electrode interactions that occur during simultaneous stimulation are not well understood. This thesis investigates the characteristics of cortical responses to simultaneous stimulation of multiple electrodes. We formulated a quantitative model to characterise the responses of visual cortex neurons to multi-electrode stimulation of the retina to understand how simultaneous stimulation can improve resolution. Activity was recorded in the visual cortex of normally sighted, anaesthetised cats in response to temporally sparse, spatially white stimulation with 21 or 42 electrodes in the suprachoroidal space of the retina. These data were used to constrain the parameters of a linear-nonlinear model using a spike-triggered covariance technique. The recovered model accurately predicted cortical responses to arbitrary patterns of stimulation, and demonstrated that interactions between electrodes are predominantly linear. The linear filters of the model, which can be considered as weighting matrices for the effect of the stimulating electrodes on each cortical site, showed that cortical responses were topographically organised. Photoreceptor degeneration results in a number of changes in the surviving cells of the retina that can negatively impact stimulation strategies. Therefore, in the second study, we investigated the effect of multi-electrode stimulation on the degenerate retina. Characteristics of cortical responses to simultaneous stimulation of multiple electrodes were evaluated in unilaterally, chronically blind anaesthetised cats, bilaterally implanted with suprachoroidal retinal prostheses. Significant differences were found between responses to stimulation of the normally sighted and blind eyes, which may help to explain the varied perceptual observations in clinical trials with simultaneous stimulation. The success of the linear-nonlinear model in predicting responses to arbitrary patterns of stimulation indicated that it may provide a basis for optimising stimulation strategies to shape cortical activity. Therefore, we investigated the possibility of inverting the model to generate stimuli aimed at reliably altering the spatial characteristics of cortical responses. An in vivo preparation with a normally sighted, anaesthetised cat showed that the response characteristics derived by the model could be exploited to steer current and evoke predictable cortical activity. Overall, these results demonstrate that cortical responses to simultaneous stimulation of both the normal and degenerate retina are repeatable, and can be predicted by a simple linear-nonlinear model. Furthermore, the interactions between electrodes are predominantly linear, and can be harnessed to shape cortical activity through inversion of the model. The method shows promise for improving the efficacy of retinal prostheses and patient outcomes.