Causal Functional Connectivity in Alzheimer's Disease Computed from Time Series fMRI data
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Functional Connectivity between brain regions is known to be altered in Alzheimer's disease, and promises to be a biomarker for early diagnosis of the disease. While several approaches for functional connectivity obtain an un-directed network representing stochastic associations (correlations) between brain regions, association does not necessarily imply causation. In contrast, Causal Functional Connectivity is more informative, providing a directed network representing causal relationships between brain regions. In this paper, we obtained the causal functional connectome for the whole brain from recordings of resting-state functional magnetic resonance imaging (rs-fMRI) for subjects from three clinical groups: cognitively normal, mild cognitive impairment, and Alzheimer's disease. We applied the recently developed Time-aware PC (TPC) algorithm to infer the causal functional connectome for the whole brain. TPC supports model-free estimation of whole brain causal functional connectivity based on directed graphical modeling in a time series setting. We then identified the causal brain connections between brain regions which have significantly different strengths between pairs of subject groups, and over the three subject groups. We used the significant causal brain connections thus obtained to compile a comprehensive list of brain regions impacted by Alzheimer's disease according to the current data set. The obtained brain regions are in agreement with existing literature published by researchers from clinical/medical institutions thus validating the approach. We then discuss the soundness and completeness of the results and the potential for using causal functional connectivity obtained using this methodology as a basis for the prognosis and diagnosis of Alzheimer's disease.
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