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Modulation of frequency-dependent EEG connectivity in Parkinson's disease

University of British Columbia

Traditional models of Parkinson's disease (PD) have emphasized the progressive degeneration of dopaminergic projections to the basal ganglia (BG). Since the advent of deep brain stimulation (DBS) surgery for PD that allows direct BG recordings, it has become apparent that PD is also characterized by abnormal oscillatory activity within BG-thalamocortical loops. Altered β band activity in particular has been shown to correlate with bradykinesia and rigidity, and appears to be suppressed by both levodopa medication and high-frequency subthalamic nucleus (STN) DBS. However, recent animal studies have suggested that the primary site of DBS action is the cortex, thus implying that cortical areas might play a greater role than previously recognized in the modulation of abnormal PD rhythms. This thesis aimed to investigate cortical connectivity modulation in frequency bands (α, β) that have been described in oscillatory models of PD, and to understand the effects of levodopa on connectivity. We utilized a sparse Multivariate Autoregressive (mAR)-based Partial Directed Coherence (PDC) method to assess frequency-dependent EEG connectivity in PD subjects and controls performing a visually guided task previously shown to modulate abnormal oscillatory activity in the STN of PD patients. In addition, we utilized traditional spectral analysis to evaluate task-dependent power modulation in five electrode regions of interest. While spectral analysis revealed power modulation differences between PD and control subjects, it showed relatively modest differences between regions. In contrast, PDC-based analysis revealed complex, region-dependent alterations of directional connectivity in PD subjects as compared to normal subjects. Connectivity was particularly altered posteriorly, suggesting abnormalities in visual and visuo-motor processing. Moreover, connectivity measures correlated with motor Unified Parkinson’s Disease Rating Scores (UPDRS) in PD subjects withdrawn from medication. Levodopa administration only partially restored connectivity, and in some cases resulted in further exacerbation of abnormalities. Overall, we suggest that the use of a PDC-based method might be ideally suited to investigate temporally-sensitive, directional connectivity changes in both the healthy and the diseased state using non-invasive EEG. Our findings have implications for the investigation of abnormal rhythms not only in PD, but also in other conditions characterized by altered oscillatory activity, such as epilepsy or schizophrenia.

Text

2010-07-23

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/26842

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/