Medical Bionics - Theses
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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.