West, Timothy;
(2020)
The Dysregulation of Synchronized Brain Oscillations in Parkinson's Disease.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
This thesis concerns the properties and emergence of pathologically synchronized brain networks in Parkinson’s disease (PD), a neurodegenerative disorder of the motor system. Excessive oscillatory power in the beta frequencies (14-30 Hz), measured from recordings of activity in the subthalamic nucleus (STN) in the basal ganglia, has been repeatedly linked to the motor impairment associated with PD. However, it is not yet known: (i) how this aberrant rhythmicity is generated; and (ii) how this activity may impair propagation of normal activity across the network. This work makes novel analyses of electrophysiological recordings from both patients with PD, as well as rodent models of the neuropathology. In patients, we use both local field potential (LFP) and magnetoencephalography recordings that were made following surgery for deep brain stimulation. In animal models, we investigate multisite LFP recordings from across the networks formed by the cortex and basal ganglia of animals with a pharmacological lesion designed to mimic the generation of dopamine neurons associated with the disease. The nature of altered local and long-distance synchronization is investigated using a combination of tools from signal analysis, dynamical systems theory, and computational modelling. I specifically address: 1) how altered synaptic connectivity arising due to dopamine depletion may lead to the emergence of pathologicallly rhythmic activity in the beta frequencies; 2) the determination of the time resolved dynamics of beta oscillations and their relationship to cortical input; 3) the plausibility of a hypothesis of a dynamical shift in PD of brain networks towards more stable states. I find evidence that the beta rhythm is pathologically synchronized across the STN and neighbouring structures of the basal ganglia, and that the propagation of normal rhythmic activity is impaired by dopamine depletion.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The Dysregulation of Synchronized Brain Oscillations in Parkinson's Disease |
| Event: | University College London |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) Licence (https://creativecommons.org/licenses/by-nc-nd/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. |
| Keywords: | basal ganglia, brain networks, oscillations, Parkinson's disease, synchronization |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10078136 |
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