Exploring Brain Functional Connectivity in Cognitively Healthy Individuals with Pathological CSF Amyloid/Tau

Abstract

AbstractBackgroundDisrupted brain connectivity precedes cognitive impairment in Alzheimer’s disease (AD), affects self‐regulation and executive functions, and can be revealed by quantitative electroencephalography (qEEG). Neuroimaging research on AD progression has demonstrated structural and functional abnormalities in specific brain regions and connections. However, little is known about the changes in directional functional connectivity in pre‐symptomatic AD. We aim to explore the information flow in pre‐symptomatic AD during cognitive flexibility challenge.MethodDuring a task‐switching challenge, 21‐head channel EEG was recorded from 55 cognitively healthy individuals classified into two groups (9 were excluded from artifacts or suboptimal performance): with an abnormal (CH‐PAT, n = 27) versus normal (CH‐NAT or controls, n = 19) ratio of cerebrospinal fluid (CSF) amyloid/total‐tau. In the task‐switching paradigm, each trial included two stimuli, and participants were required to either name the ink color or read the word when color words were printed in different colors of ink. Only correctly responded trials were analyzed. Directed functional connectivity between brain regions was estimated with Partial Directed Coherence (PDC) in frontal, central, parietal, temporal, and occipital regions in alpha frequency band (8‐12 Hz) during word‐color trials. Two‐sided t‐tests were conducted, with p<0.05 considered the level for significance. No multiple comparison correction was used for this exploratory study.ResultPilot analysis shows significant differences between CH‐PATs and CH‐NATs: CH‐PATs has shown decreased information flow from the temporal and occipital regions compared to CH‐NATs with p‐values of 0.001 and 0.04, respectively. In addition, frontal brain regions have shown enhanced information flow in the CH‐PATs compared to CH‐NATs (p = 0.02) (Figs 1&2). Moreover, greater information flow between the medio‐frontal cortex and occipital regions was observed in CH‐PATS than CH‐NATS (Fig 1).ConclusionCompared to CH‐NATs, the enhanced connectivity in frontal regions in CH‐PATs suggests that their frontal brain regions are compensating for the damage caused by the amyloid/tau pathology. The decreased information flow from temporal and occipital regions in CH‐PATs may indicate a loss of relative functional importance of these regions. Our exploratory findings provide a novel and alternative approach for connectivity‐based analysis to identify the effects of amyloid/tau pathology in CH participants.