Zarkali, Angeliki; (2021) The Neural Correlates of Visual Hallucinations in Parkinson's Disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Visual hallucinations are common in Parkinson’s disease (PD) and linked to worse outcomes: increased mortality, higher carer burden, cognitive decline, and worse quality of life. Recent functional studies have aided our understanding, showing large-scale brain network imbalance in PD hallucinations. Imbalance of different influences on visual perception also occurs, with impaired accumulation of feedforward signals from the eyes and visual parts of the brain. Whether feedback signals from higher brain control centres are also affected is unknown and the mechanisms driving network imbalance in PD hallucinations remain unclear. In this thesis I will clarify the computational and structural changes underlying PD hallucinations and link these to functional abnormalities and regional changes at the cellular level. To achieve this, I will employ behavioural testing, diffusion weighted imaging, structural and functional MRI in PD patients with and without hallucinations. I will quantify the use of prior knowledge during a visual learning task and show that PD with hallucinations over-rely on feedback signals. I will examine underlying structural connectivity changes at baseline and longitudinally and will show that posterior thalamic connections are affected early, with frontal connections remaining relatively preserved. I will show that PD hallucinations are associated with a subnetwork of reduced structural connectivity strength, affecting areas crucial for switching the brain between functional states. I will assess the role of the thalamus as a potential driver of network-level changes and show preferential medial thalamus involvement. I will utilise data from the Allen Institute transcription atlas and show how differences in regional gene expression in health contributes to the selective vulnerability of specific white matter connections in PD hallucinations. These findings reveal the structural correlates of visual hallucinations in PD, link these to functional and behavioural changes and provide insights into the cellular mechanisms that drive regional vulnerability, ultimately leading to hallucinations.

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