Medical Bionics - Theses

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    Preclinical investigation of electrical field shaping strategies for retinal prostheses
    Spencer, Thomas Charles ( 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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    Investigating the effect of focused multipolar stimulation for cochlear implants: preclinical studies
    Sam George, Shefin ( 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.