Neuroimaging studies of brain networks in Parkinson’s Disease
File(s)
Author(s)
Loane, Clare
Type
Thesis
Abstract
Parkinson’s disease (PD) is a common, disabling, neurodegenerative disease characterised by three core motor symptoms: tremor, rigidity and bradykinesia. These symptoms arise from degeneration of dopaminergic (DA) cells in the substantia nigra (SN) and the subsequent loss of dopaminergic terminals within the striatum, and circuits to cortical areas, critical in the control of movement. Other, non-DA systems are now known to be involved in the pathogenesis of PD, defective cognitive functions and side effects of DA medication treatments. Thus, the use of non-invasive in vivo techniques such as magnetic resonance imaging (MRI) has allowed a reliable, albeit in-direct method of assessing alterations in the PD brain. It is now widely considered that motor control is dependent upon the integrated operation of large-scale distributed brain networks. Recent methodological advances in MRI techniques allow both structural and functional connectivity between critical regions of motor control to be investigated and increase our understanding of the impact of PD pathology on motor networks and its subsequent effect on symptomatology. In this thesis, I present three studies that combine both structural and functional MRI techniques to assess the neural PD motor network and to test the general hypothesis that loss of effective motor control in PD arises from disrupted connectivity. I demonstrate in a sizable cross-sectional study that as disease burden increases, effective functioning in key motor areas and functional connectivity between regions in both the active and resting state is initially compromised but does show evidence of compensatory mechanisms. In addition, I show that compensatory mechanisms are likely to possess a neural reserve property rather than permit a period of normal functioning. Next, I present a follow-up study that assessed the active and resting neural motor network longitudinally. This study clearly shows that functional connectivity of the active and resting neural motor network is compromised as the disease progresses with evidence suggesting the initiation of compensatory mechanisms. Finally, structural properties of key regions related to PD pathology (substantia nigra and striatum) have been assessed to elucidate the effect of PD progression on diffusion indices and clinical symptoms. This work identifies the importance of multi-modal assessment of neural networks in PD to evaluate the effect of disease on neural motor control.
Version
Open Access
Date Issued
2015-06
Date Awarded
2016-01
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Piccini, Paola
Publisher Department
Department of Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)