Medical Bionics - Theses
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ItemBehavioural and objective measurements of listening effort( 2021)Listening effort has been defined as the mental effort exerted to understand auditory stimuli (Pichora-Fuller et al, 2016a). In many cases it is one of the causes of isolation and poor quality of life for people with hearing aids and cochlear implants. One way to mitigate this problem is to assess listening effort during the fitting of hearing devices and then use these measurements to optimise device settings to improve audibility while at the same time minimising listening effort. However, at the moment, clinical practice lacks a standardised protocol for the assessment of listening effort. In this project, a behavioural test for the assessment of task difficulty was developed and validated. As was the feasibility of using fNIRS for the assessment of listening effort. The first study in this thesis focused on the development and validation of a behavioural dual task test for assessment of task difficulty. The test consisted of identification of the last word of each sentence in lists of seven sentences each, and recall of those last words after the presentation of each list. The test was implemented with Australian speech material, to minimise possible confounding factors due to accent and dialect dissonances when applied to the Australian population. The test was applied to twenty-four normal hearing participants. The results showed that, both identification and recall scores could predict differences in difficulty between speech presented in noise and speech presented in noise in which a binary mask noise reduction algorithm was applied to the speech mixture. The implemented test could be used in the Australian research practice to compare different hearing devices and processing algorithms at high levels of speech intelligibility. The second study investigated the feasibility of using fNIRS for assessment of listening effort. More specifically, in this study fNIRS was used for identifying cortical neuronal biomarkers of listening effort in the left inferior frontal gyrus (LIFG) and bilateral posterior superior temporal gyrus (pSTG). The findings of the study suggest the existence of task related concentration changes of oxy- and deoxy- haemoglobin during the expected exertion of listening effort. Furthermore, when listening effort was modulated by manipulation of motivation and task demands, the change in concentration of oxyhaemoglobin, followed the behaviour expected for listening effort. However, the results of this study were not statistically significant due to the high level of uncontrolled variability on the data. These results suggest a potential for fNIRS in the assessment of listening effort, however, more investigation needs to be done to optimise the protocols for assessment of listening effort and improve effect size. The third study continued with the investigation of the feasibility of using fNIRS for the assessment of listening effort. However, in this study, rather than using fNIRS for monitoring cortical neuronal activity, it was used for monitoring concentration changes of total haemoglobin in the extracerebral compartment (scalp and skull), associated with the activation of the autonomic nervous system. The findings of this study suggested the existence of task related concentration changes of total haemoglobin in the extracerebral compartment. When compared with the expected behaviour of listening effort modulated by manipulation of motivation and task demands, it was found that the concentration changes of total haemoglobin in the extracerebral compartment followed the expected trend of behaviour of listening effort, but again, these results were not statistically significant. The results suggests that fNIRS could potentially be used for assessment of listening effort, not just due to the capability of monitoring cortical neuronal activity, but also due to the capability of monitor activation in the autonomic nervous system. In this project, behavioural and objective measurements of listening effort were investigated. The work reported in this thesis has shown that behavioural methods can be used for assessment of listening task difficulty. But also, the experiments reported in this thesis investigated the feasibility of fNIRS for the assessment of listening effort. It was determined that fNIRS has the potential for assessment of listening effort because it facilitates the study of its different aspects, associated with cortical neural activity, but also, with activation of the autonomic nervous system when listening under challenging conditions. This work provides a base for future research that should be focused in determining a protocol for measurement of listening effort that integrates cortical neuronal and systemic components extracted from the fNIRS signal to better understand listening effort.
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ItemIdentifying and addressing limitations in deep brain stimulation for Parkinson's disease using novel neuronal biomarkers( 2020)Deep brain stimulation (DBS) is an effective treatment in Parkinson’s disease (PD). DBS is postulated to modulate and restore ‘functionality’ to the pathological brain networks implicated in PD. DBS therapy improves motor symptoms and quality of life and allows for substantial medication reduction. However, there is little information on the long-term outcomes after DBS implantation including programming rates, battery changes, hardware complication surgeries or the duration of the therapy. This knowledge is crucial to inform on clinical decision making, distribution of healthcare resources and guide research direction for device development. The first part of this thesis presents a cross-sectional, population-based study of 1849 patients with PD implanted with DBS in Australia over a 15-year period (2002-2016). Individual-level patient data was derived from three linked national government databases and the requirements for DBS care and servicing was evaluated, referenced from the time of surgery. The mean annual programming rate was 6.9 in the first year, and 2.8 annually thereafter. Over 50% of patients required repeat hardware surgery after DBS implantation. 11.3% of patients had repeat intracranial electrode surgery (including 1.1% of patients who were completely explanted). 47.6% of patients had repeat implantable pulse generator/extension-cable surgery including for presumed battery depletion. 6.2% of patients had surgery of the implantable pulse generator /extension-cable surgery within one year of any previous such surgery. 30-day post-operative mortality was 0.3% after initial DBS implantation and 0.6% after any repeat hardware surgery. The median time from DBS surgery to residential care admission was 10.2 years and, to death was 11.4 years. These findings support development of technologies to reduce therapy burden such as enhanced surgical navigation, hardware miniaturisation and improved battery efficiency. The second part of the thesis focuses on two key contributors to DBS therapy burden, device programming and electrode redo surgery. DBS efficacy relies on the delivery of stimulation to the ideal location to achieve optimal motor benefit. This site is determined by the electrode location and the contact selected to apply DBS by the clinician. DBS programming is an arduous, time-consuming process, and highly dependent on clinician expertise. Neuronal signals have been proposed as biomarkers to assist in DBS programming and guide electrode implantation. The most widely studied signals are local field potentials (LFPs) such as beta oscillations and high frequency oscillations (HFO). However, LFPs hold recording challenges due to their small size and low signal to noise ratio. More recently, our group has described an evoked potential, elicited by DBS, termed ‘evoked resonant neural activity’ (ERNA). ERNA is a large amplitude signal, with a characteristic decaying oscillation morphology, that is reliably recordable in patients with PD implanted with subthalamic nucleus (STN) DBS. It localises to the postulated ideal anatomical location to apply DBS, in the dorsal STN. However, the clinical relevance of ERNA and its utility compared to LFPs or electrode anatomical location is unknown. Thus, in 50 (100 hemispheres) consecutive patients with PD implanted with STN DBS, ERNA power, beta power and HFO power was measured from each of the four contacts on the DBS lead during surgery. Neuroimaging was obtained peri-operatively to visualise each contact and determine its proximity to a nominated ideal anatomical location. The four contacts in each hemisphere were ranked from one to four according to neuronal signal power and anatomical location. In 14 patients (28 hemispheres), therapeutic stimulation was applied to each of the four contacts on the DBS lead and the degree of motor benefit measured. ERNA, beta oscillations and the anatomical location of contacts similarly predicted how motor benefit varied across contacts with STN DBS therapy. Combining ERNA, beta and HFO ranking data yielded the strongest predictive model. However, only first-ranked contacts according to ERNA delivered a motor benefit that was significantly better than at the other three contacts on the lead. Furthermore, only first-ranked ERNA contacts delivered a motor benefit that was not significantly less than the maximal available in each hemisphere. When monopolar configuration was chosen at 6 months after DBS surgery, the clinician-chosen contact corresponded most frequently with the first-ranked ERNA contact in 81% of hemispheres compared to 71% for anatomy and 52% for beta. ERNA performed significantly better than anatomy and beta oscillations and combining data using machine learning algorithms did not improve model performance compared to using ERNA data alone. These results support the role of ERNA in guiding contact selection and assisting intra-operative electrode navigation to ultimately, reduce the treatment burden of DBS therapy.
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ItemOculomotor Behaviour and Perceptual Localisation in Retinal Prostheses( 2020)Prosthetic vision is an emerging technology aiming to provide artificial vision to the profoundly blind. Present-day visual prostheses provide useful assistance in everyday life but the quality of vision is poor, with only fractional visual field coverage and limited resolution of detail. The retina, optic nerve, or primary visual cortex are electrically stimulated using implanted electrodes to elicit artificial visual percepts. Eye movements cause movement of the percept within the visual field, however, in many devices, electrode activity is modulated by images captured by a head-mounted camera that does not move in conjugate with eye movement. Percept locations are therefore dissociated from the real-world, leading to localisation errors. Users must be trained to use head movement, rather than eye movement, to control the camera, potentially increasing the difficulty of using the device for every-day activities. This thesis explores oculomotor behaviour in prosthetic vision and investigates the use of eye tracker feedback to redirect the video input in real time (‘gaze compensation’) to restore naturalistic control of gaze. The first study presented in the thesis investigated the effect of visual field loss on eye and head movement coordination in low-vision subjects with retinitis pigmentosa (RP), the current primary indication for retinal prostheses. Visual field loss was found to be associated with a habitually confined range of eye movement and a greater reliance on head movement. This has implications for training and rehabilitation in visual prostheses, as recipients with RP express atypical eye and head scanning behaviour. An investigation of the oculomotor behaviour of retinal prosthesis recipients in a forced-choice localisation task and a motion discrimination task is also presented. Although the participants were aware of the potential for eye movements to impair task performance, systematic eye movements were observed in response to the task stimuli. These were interpreted as reflexive eye movements made in response to the static and dynamic stimuli, as would be expected in normal vision, suggesting preserved oculomotor capacity. This is a promising indication for the naturalistic integration of artificially evoked percepts into the visual system, but the primary purpose of these eye movements, namely foveation, cannot be fulfilled without gaze compensation. Following the demonstration of naturalistic eye movement in retinal prosthesis users and the finding that suppression of eye movement was difficult or impossible, the thesis then examines the effect of eye movement on localisation and the possible benefits of gaze compensation. It was found that eye movement lead to localisation errors in a target localisation task in simulated prosthetic vision, but the introduction of gaze compensation resolved this. A subsequent pilot study in retinal prosthesis recipients is also presented, in which no benefit of gaze compensation for localisation was observed, possibly because the subjects had learned compensatory strategies. However, some methodological problems were identified, and similar studies from a different group do show a benefit of gaze compensation. Overall the thesis advances the understanding of the perceptual experience and oculomotor behaviour of visual prosthesis users and argues for the integration of gaze compensation in camera-based visual prostheses.
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ItemThe utility of an instrumented pull test to evaluate postural instability in Parkinson’s disease( 2019)Postural instability is one of the cardinal symptoms of Parkinson’s disease (PD). Postural instability can present on diagnosis, and commonly becomes more prominent with disease progression, resulting in subsequent falls and diminished quality of life. The treatment of postural instability is challenging, as it is often refractory to management with levodopa and deep brain stimulation of conventional targets such as the subthalamic nucleus. To assess postural instability, the most commonly used measure in the clinical setting is the pull test according to item 30 of the Unified Parkinson’s disease rating scale (UPDRS), where an examiner performs a brisk backward tug at the patient’s shoulder level and grades the corrective response. While easy to administer, outcomes can vary due to variability in test administration and interpretation. A comprehensive literature review revealed laboratory based assessments provided a more objective method to measure postural responses compared to clinical assessments in people with PD. These techniques were conventionally employed in people with PD in later disease stages who already demonstrate postural instability. Laboratory based assessments presented a method to identify abnormalities before postural instability is clinically evident and effects of therapies. The recent development of instrumentation of clinical balance tests offered an alternative technique to precisely quantify postural responses. Here, we developed an instrumented version of the pull test and investigate its utility to quantify postural instability in people with PD ranging from mild to moderate disease severity. In Study 1, the sensitivity of the instrumented pull test was investigated in healthy young participants. Postural responses were modified by presenting a startling auditory stimulus concurrent with the backwards pull. Such stimuli evoke StartReact effects and are known to speed reaction times. The instrumented pull test could detect small 10 ms decreases in postural reaction time evoked by the startling stimulus. The ability to detect such changes in healthy individuals highlights the utility of instrumented techniques and justifies further investigation in people where changes to balance is of interest. Subsequently, the instrumented pull test was used to characterise postural responses in eighteen people with mild PD (Hoehn and Yahr less than 2) in Study 2. Subclinical abnormalities in trunk and step responses were detected in participants with mild PD compared to healthy controls. Furthermore, levodopa did not restore postural responses in participants with PD to that of healthy controls (Study 3). These findings demonstrate changes to postural stability can occur in mild disease. Abnormalities of postural responses which remain refractory to levodopa also suggest non-dopaminergic pathways may be implicated in the pathophysiology of postural instability in mild PD. Pedunculopontine deep brain stimulation (PPN DBS) is a therapy developed specifically to alleviate axial symptoms of gait and postural abnormalities unresponsive to conventional therapies such as levodopa. In Study 4, the instrumented pull test was used to quantify postural responses in five people with PD and moderate to severe postural instability receiving PPN DBS. Off and on stimulation, the instrumented pull test was able to detect postural responses with greater resolution compared to clinical assessments (axial items 27 to 30 of the motor subsection of the Unified Parkinson’s disease rating scale (UPDRS) and the Mini-BESTest. However, the use of the instrumented pull test, and interpretation of findings was limited by the small sample size and highly variable postural responses in participants with moderate to severe postural instability. On stimulation, improvement in overall balance scores was demonstrated across all participants with the Mini-BESTest but not axial items of the UPDRS. This thesis demonstrated the utility of the instrumented pull test as a potential assessment tool to evaluate postural instability in PD. Identification of postural abnormalities provides valuable insights in the assessment and management of postural instability in people with PD. Clinicians should consider that subclinical postural abnormalities can be present in people with mild PD, even when patients are on levodopa. Findings from this thesis strongly support the need for further studies to explore variables of postural responses that may be useful to detect people with PD at risk of falls and for clinicians to deliver targeted interventions earlier in disease course.
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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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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.
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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.
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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.
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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.