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.