Project - SHINE LAB
Research Project Description
The primary aim of this proposal is to apply a novel approach to understand the role of the ascending noradrenergic arousal system in visual hallucinations in Parkinson’s disease (PD). I will combine my skills in pupillometry analysis with Dr. Shine’s expertise in functional neuroimaging to create a unique insight into an often-overlooked symptom of PD, advancing our understanding of visual hallucinations (VH) and the progression of dementia in PD. Moreover, we will interrogate the functional dynamic interactions between a range of different neuromodulator systems and their joint role in cognition in health and disease. Specifically, I will:
1. Identify abnormalities in the functional interaction between large-scale neuronal networks in patients with PD during the performance of cognitive tasks specifically designed to elicit VH;
2. Relate the abnormal brain network dynamics during VH to fluctuations in pupil diameter, which is an index of noradrenergic arousal;
3. Refine our understanding of the role of different neuromodulator systems in non-motor symptoms in PD.
If successful, this project will significantly advance our understanding of VH in PD and will lead to a number of potential directions for therapeutic intervention strategies and further research. Moreover, the results will disentangle the currently opaque functional interactions between the noradrenergic, dopaminergic and cholinergic systems. Finally, the project would also improve my ability to conduct cutting-edge neuroimaging analyses, which then form the foundation of my graduate studies.
To probe the hypothesis of this PhD, we will apply a novel Bistable Percept Paradigm (BPP) task developed by Dr Shine and colleagues3 that has previously been used to successfully separate individuals with VH and PD from a group without VH. I will add to this work by studying fluctuations in pupil diameter while participants perform this task in an fMRI scanner. In this manner, I will be able to correlate changes in the ascending neuromodulator system (via the pupil) and the large-scale dynamics in the brain (via fMRI scans). We predict that patients with VH will have a lower pupil diameter activity and heightened large-scale network segregation, both of which are predicted to be caused by impaired ascending noradrenaline. In this way, our work will allow us to compare different aspects of behaviour, brain dynamics and pupillometry in a diverse group with different brain conditions. Finally, we will correlate the different patterns of brain network activity to the density of neurotransmitter receptor patterns from other neuromodulators systems (such as the cholinergic, dopaminergic and serotonergic system) using the Allen Brain Atlas (http://www.brain-map.org). The results of this study will point towards potential pharmacological therapies for patients with visual hallucinations. In short, we will use this analysis pipeline to disentangle the neuromodulator concerto18 that drives cognition in health and disease.