Medical Bionics - Theses
Permanent URI for this collection
Search Results
1 - 6 of 6
-
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.
-
ItemExploring the use of diamond in medical implants( 2018)Over recent decades, there is increasing interest in implantable devices that interact with neural tissue in the human body. Applications are broad, ranging from cardiac pacemakers to cochlear implants and beyond. The emergence of microelectronics and microfabrication has led to the miniaturization of these neural implants. Small devices are safer to implant but a number of challenges need to be addressed before very small devices are routinely deployed. For instance, it is difficult to transfer sufficient power to small implants wirelessly, and difficult to fabricate small neurostimulation microelectrodes with high enough charge injection capacity to operate safely. Compounding this, the immune system of the body can react to the implant. Unfavourable interactions of the electrode with tissue/neurons leads to a sharp drop in performance caused by scar tissue surrounding them. These challenges, among others, must be overcome in order to reduce the size of implants into the low millimeter dimensions. Devices at this scale will be insertable with minimal trauma and will hence be deployable in a greater range of circumstances. Here we investigate the use of diamond as a biomaterial with the potential to mitigate or ameliorate some of these challenges. In this work, a novel technique for microcoil fabrication is introduced. Trenches were milled into a diamond substrate and filled with silver active braze alloy, enabling the manufacture of small, high cross-section, low impedance microcoils capable of wireless power transmission of 10 mW over 6 mm. The coils were encapsulated in a second layer of diamond, characterized, and accelerated ageing was performed to verify the longevity of the construct. Building on previous work, a method was developed to grow conducting diamond films on platinum foil. A laser roughening method was used to increase adhesion of the diamond to the platinum. This approach enables the superior properties of diamond to be integrated into devices constructed using traditional fabrication methods such as wire bonding or laser welding. Laser roughened platinum was coated with nitrogen induced ultra-nanocrystalline diamond (N-UNCD) films and the electrochemical performance of these films was measured relative to platinum. Stronger attachment of N-UNCD to platinum substrates of higher roughness was observed. Diamond on platinum electrodes were found to be more capacitive and stable compared to platinum controls, a favorable characteristic for neural stimulation. Finally, an extracellular matrix protein (laminin) known to be involved in inter-neuron adhesion and recognition, was covalently coupled to diamond electrodes. Biologically, active interlayers have the potential to increase neural adhesion to electrodes and/or reduce the immune response, thus increasing longevity. Electrochemical analysis found that covalently coupled films were robust and resulted in minimal change to electrochemical properties of the electrodes. Neurons cultured on laminin coated surfaces exhibited improved adhesion. This thesis demonstrates that diamond is a versatile material for use in medical implants. It can be used as a construction material and as an encapsulant containing electrically active elements. It can be made electrically conductive and possesses suitable electrochemical properties for neural stimulation. Finally, it can be employed as a chemically active substrate for attachment of additional chemistries, including biomolecules.
-
ItemRate modulation and speech perception with cochlear implants( 2018)While cochlear implants (CI) have been successful in restoring a sense of hearing to people with severe to profound sensorineural hearing loss, there is still a wide variance in speech outcomes for CI users. Psychophysical experiments have shown that some of the variance can be explained by sensitivity to temporal modulations. If poor outcomes are partly caused by limited access to temporal speech cues, then improved transmission of those cues may provide perceptual benefits to CI users. The broad aim of the research presented in this thesis was to improve speech outcomes for CI users through better transmission of temporal speech information. The first study investigated the effect of stimulation rate and presentation level on speech perception and temporal modulation detection for CI users, in order to identify stimulation rates that provide a perceptual advantage in certain listening conditions. Speech perception (in quiet and in noise) and amplitude modulation detection thresholds (AMDTs) were measured at different presentation levels and stimulation rates. The reduction in speech perception due to added noise was significantly greater at higher rates. Speech perception was also significantly affected by presentation level, with scores increasing as the level increased. In contrast, AMDTs, as measured via acoustic input to the speech processor, exhibited no effect of rate or level. Correlations were found between AMDTs and speech perception for both the low-rate and high-rate processors. Therefore, while AMDTs explained inter-subject variability in speech perception, they did not explain within subject variability across stimulation rates and presentation levels. The second study evaluated the perception of amplitude modulation (AM) and rate modulation (RM), providing fundamental information about the temporal processing abilities of CI users and the perceptual mechanism underlying those abilities. The study was the first psychophysical evaluation of AM and RM detection in the same CI users. AM and RM detection thresholds were correlated and exhibited similar effects of modulation frequency and presentation level, indicating that AM and RM may be perceived by a common perceptual mechanism that involves central temporal integration. In the final study, a novel speech processing strategy called ARTmod (Amplitude and Rate Temporal modulation) was developed and tested. The ARTmod strategy encoded speech with simultaneous AM and RM, in order to observe whether RM can be used to enhance the perception of temporal envelopes of speech signals. In the experiment, the amount of AM was fixed and the amount of RM was varied, and speech perception was measured for the different RM amounts. A significant effect of RM amount was found, with speech scores improving as the RM amount was increased. The results indicated that RM can constructively combine with AM to enhance the perception of temporal speech envelopes and improve speech perception for CI users.
-
ItemLanguage processing in cochlear implant users using fNIRS( 2018)Cochlear implant (CI) users differ in their auditory speech understanding ability. This variability is partly due to variability in deafness history and pathology, and partly due to functional brain changes that are likely to occur during deafness and after implantation. By measuring cortical activity in CI users, a relation between functional changes in language associated regions of their brain and speech understanding may be revealed. However, when investigating cortical activity in CI users, commonly-used neuroimaging techniques have limitations. For example, EEG and fMRI may suffer from magnetic or electrical artefacts, and PET imaging is invasive for participants. The studies described in this thesis used a non-invasive technique – functional near-infrared spectroscopy (fNIRS) – to investigate cortical activity in CI users related to speech understanding and the integration of audio-visual speech cues. Compared to fMRI, fNIRS also has the advantages of being quiet (not suffering from the loud magnetic scanning noise) thus suitable for auditory-related tasks, and more tolerant of body movement. The first study determined whether fNIRS measures of cortical activity in post-lingually deafened CI users when listening to or watching speech are correlated with their auditory speech understanding. The fNIRS results showed that speech-evoked cortical activity in CI users that was not only different from normal-hearing listeners but also was negatively correlated with the speech understanding ability. That is, CI users who had poorer auditory speech understanding ability showed higher fNIRS activation in certain brain regions of interest when listening to or watching speech. The increased brain responses might be related to brain functional changes that occurred in CI users during deafness and after implantation for visual speech processing or more listening effort and more neural responses that were used by CI users to process auditory speech. The second study determined whether audio-visual (AV) integration of speech cues in post-lingually deafened CI users is different from that in their similar-aged normal-hearing adults. Participants’ reaction times, response accuracy, and cortical activity were measured when performing different speech identification tasks. A novel method was proposed that combined a probability model and a cue integration model to quantify the amount of AV integration based on response accuracy measures. Consistently, behavioural results using response accuracy and reaction time measures did not show better AV integration in CI users compared to people who had normal hearing. In addition, fNIRS measures of cortical activity did not show AV integration in either CI users or normal-hearing adults. The third study determined whether aging affects AV integration in people who have normal hearing when responding to speech using the same behavioural and fNIRS measures as in the second study. Again, fNIRS results did not show AV integration in either younger or older participants. Behavioural results found no significant difference in AV integration between the older and young participants using both reaction time and response accuracy measures. This thesis integrates knowledge from multisensory neuroscience and psychophysics and uses a novel brain imaging technique to measure cortical activity in CI users for language processing. Results in this thesis showed that this novel imaging technique – fNIRS – could be implemented to examine the variances in auditory speech understanding among CI users. It makes a new advance in the way that multisensory abilities are measured behaviourally, by combining models of optimal and minimum integration. Results in this thesis found that there was no significant difference between CI users and normal-hearing adults in the integration of audio-visual speech cues. Neither was there a significant effect of aging on AV integration.
-
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.
-
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.