Medical Bionics - Theses
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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.
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ItemInvestigating the effect of focused multipolar stimulation for cochlear implants: preclinical studies( 2016)Multichannel cochlear implants have been well accepted as an effective and safe treatment for severe to profound sensorineural hearing loss through electrical stimulation of residual spiral ganglion neurons. However, speech intelligibility with existing cochlear implants is thought to be limited by poor spatial selectivity and interactions between channels caused by overlapping activation with contemporary stimulation strategies such as monopolar (MP) stimulation. Focused intracochlear stimulation, resulting in an increase in the number of truly independent stimulating channels available for simultaneous activation, may enable better speech and pitch recognition and also improve temporal resolution. Various current focusing stimulation strategies such as tripolar (TP) stimulation have been reported to produce sharper excitation patterns and reduced channel interactions compared to MP stimulation at the cost of higher stimulation current levels. Focused multipolar (FMP) stimulation is another such focusing technique; utilizing simultaneous stimulation of multiple channels to create focused electrical fields. FMP stimulation has been validated in a small group of cochlear implant recipients showing that focusing can be achieved, however this was at the expense of higher stimulation currents compared to MP stimulation. There have been no previous attempts to systematically compare the efficacy of FMP stimulation against TP stimulation or to determine whether factors such as neural survival and the electrode position within the cochlea would affect the performance of FMP stimulation. Controlled preclinical studies in experimental animals can reduce the possible confounding effects of neural survival in human studies. It is also important to test if FMP produces non-auditory sensations since the simultaneous nature of the stimuli would be expected to require greater charge to evoke neural responses. The primary objectives of this thesis were to determine the efficacy of FMP stimulation, compared to both MP and TP stimulation, by evaluating a) the spatial extent of neural activation b) interactions between cochlear implant channels and c) modulation sensitivity to sinusoidal amplitude-modulated pulse trains. The effects of factors such as degeneration of spiral ganglion neurons, induced by long-term deafness, and the electrode position within the cochlea on the effectiveness of FMP, TP and MP stimulation were also examined. These objectives were achieved by implanting a multichannel cochlear implant into cats and guinea pigs, and recording the neural responses in the inferior colliculus in acute electrophysiological experiments. Neural thresholds and the spread of activation along the tonotopic gradient were measured. In summary, the main results of this thesis showed that FMP and TP stimulation resulted in more restricted neural activation and reduced channel interaction compared to MP stimulation and these advantages were maintained in cochleae with significant neural degeneration. Moreover, these effects were not adversely affected by the position of the electrode array within the scala tympani. Although greater charge was required to achieve threshold levels, no evidence of ectopic stimulation of non-auditory neurons was observed with FMP or TP stimulation. Systematically varying the degree of current focusing lowered threshold levels for FMP stimulation while still maintaining a selectivity advantage. Modulation detection of MP was found to be significantly better than FMP and TP stimulation at low stimulation levels, but similar at high stimulation levels. Importantly, there was no benefit in terms of restricted neural activation, reduced channel interaction or better modulation sensitivity for FMP compared to TP stimulation. The greater spatial selectivity, reduced channel interactions and the ability to convey modulation using FMP and TP stimulation would be expected to result in improved clinical performance. The insights into current focusing described in this thesis may also be helpful in other neural prostheses such as deep brain stimulation devices and visual prostheses, when more selective stimulation is desired.
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ItemPeripheral nerve stimulation for the treatment of chronic neuropathic pain( 2014)Neuropathic pain is a chronic health condition with a severe impact on the quality of life of affected patients. The condition is often difficult to manage and refractory to traditional pain treatment strategies such as pharmacological management, physiotherapy and psychological therapy. Peripheral nerve stimulation has been proposed as an alternative treatment with numerous successful clinical reports. Nevertheless, the systematic understanding of the underlying mechanism of action is still limited. Efficacy studies in the form of randomised controlled trials have predominantly been conducted for occipital nerve stimulation to treat various headache conditions. Without trials of a wide range of neuropathic conditions, the commercial availability of approved medical devices is limited. The overall objective of this thesis was to advance towards the development of a peripheral nerve stimulation system for a small-scale clinical trial that will be used to gain a deeper understanding of the underlying mechanisms of pain modulation. Design features of electrode arrays and new stimulation strategies were tested in order to facilitate the development of advanced clinical peripheral nerve stimulation systems. The first part of the work consisted of the development of a small, wearable neural stimulator for the use in clinical trials. Chapter 2 presents the design and characterisation of the stimulator. It was shown that safe and efficacious neural activation could be achieved and the system will be suitable for use during a short-term clinical trial of electrode arrays with a percutaneous leadwire system. In the second part, a model electrode setup was used to investigate a bipolar stimulation strategy. Chapter 3 documents an electrophysiological study on the maximisation of the therapeutic window available for stimulation. An electrode screening strategy was developed in order to increase the efficiency of intra- and post-operative testing of stimulation arrays with a large number of electrode combinations. The third part of the work focussed on the development of single-source multipolar stimulation as a novel method to perform current focussing for increased selectivity of the neural activation. Chapter 4 presents the in vitro investigation that showed that a successful reduction of voltages at electrode sites other than the centre electrode was achieved when compared to monopolar stimulation. Furthermore, a significant improvement of the voltage reduction was also found compared to tripolar and common ground stimulation. The promising results from the in vitro tests were followed by an in vivo evaluation as presented in Chapter 5. However, the focussing effects found in vitro did not translate to functional benefits in vivo for the investigated setup. Rather, increased neural activation thresholds were found resulting in potentially higher power requirements for a clinical system. Monopolar stimulation was identified as the favourable mode under the tested conditions. In conclusion, the results of this thesis suggest that a safe and reliable, tailored electrode array in combination with a monopolar stimulation strategy forms a promising system in order to progress towards the overall objective, a short-term clinical trial. This will help to gain a deeper understanding of the underlying mechanism of action of peripheral nerve stimulation for the treatment of chronic neuropathic pain.