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Advanced network analysis of resting-state functional connectivity to probe executive function in Parkinson's Disease and Multiple Sclerosis

University of British Columbia

This thesis is to probe the systems-level neurobiological bases for executive function in patient populations overarchingly. We focus on two representative diseases, Parkinson’s Disease (PD), and Multiple Sclerosis (MS), as although they have different pathologies, patients often result in similar cognitive deficits. We examine resting-state fMRI data from both PD and MS subjects with novel methods in a network fashion. We employ advanced connectivity analyses to evaluate graph theoretical, static and dynamic resting-state functional connectivity (rsFC) measures. Multivariate statistical methods such as Canonical Correlate Analysis (CCA) and Multiset Canonical Correlate Analysis (MCCA) are used to robustly link rsFC and cognitive performance. PD data used in the thesis research include three cohorts: Parkinson’s Progression Markers Initiative (PPMI) and two research projects conducted at UBC (project name: BCT and GFM2). For MS, two cohorts are included: OPERA MS clinical trial and COGMS research project, which are both conducted at UBC. After a general introduction in the first chapter, in the second chapter we examine multivariate relations between demographic and cognitive profiles with CCA, showing that female gender is associated with better cognitive performance in both diseases possibly due to protective effects of estrogen. In chapter 3, we use correlation to assess functional connections. Both diseases have significantly altered interhemispheric connectivity, which is associated with altered cognitive performance in MS, but not PD. In chapter 4, we utilize graph theoretical approaches and find increased segregation of rsFC in PD, supporting a previously-proposed model of vulnerability of hubs in disease populations. In MS, higher modularity of the rsFC network is correlated with better executive skills. In chapter 5, we explore dynamic rsFC and discover that longer disease duration in MS is associated with decreased dynamic rsFC. In both populations, dynamic interhemispheric connectivity is robustly associated with cognitive abilities. In chapter 6, MCCA is applied to jointly explore the associations between dynamic and stationary rsFC, and behavioural measures. In MS, better executive functioning is supported by higher education, stronger and dynamic rsFC; in PD, better memory function is related to segregated brain networks and dynamics of interhemispheric connections. Chapter 7 summarizes and concludes these chapters.

Text

2018-08-27

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/66940

Neuroscience

University of British Columbia

UBCV

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