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 perform an exploratory analysis to identify the causal brain connections between brain regions which have altered strengths between pairs of subject groups, and over the three subject groups, based on edge-wise p-values from statistical tests. We used the altered 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 brain regions thus identified are found to be in agreement with literature on brain regions impacted by Alzheimer's disease, published by researchers from clinical/medical institutions.

翻译：已知阿尔茨海默病会改变脑区间功能连接，且该连接有望成为该疾病早期诊断的生物标志物。尽管多种功能连接方法可获取表征脑区间随机关联（相关性）的无向网络，但相关关系并不必然蕴含因果关系。相比之下，因果功能连接更具信息量，能提供表征脑区间因果关系的定向网络。本文基于静息态功能磁共振成像（rs-fMRI）记录，针对认知正常、轻度认知障碍及阿尔茨海默病三个临床组别的受试者，获取了全脑因果功能连接组。我们采用近期发展的时间感知PC（TPC）算法推断全脑因果功能连接组，该算法支持基于时间序列设定下定向图建模的无模型全脑因果功能连接估计。随后通过探索性分析，基于统计检验的边级p值，在配对受试组间及三个受试组整体层面，识别强度存在差异的因果脑连接。我们利用由此获得的差异因果连接，编制了当前数据集中受阿尔茨海默病影响的脑区综合列表。所识别的脑区与临床/医疗机构研究者发表的阿尔茨海默病相关脑区文献结果一致。