Cardiorespiratory fitness as a predictor of effective connectivity in the default mode network
Kronman, Corey Alexander
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Previous work has linked the onset and progression of Alzheimer’s Disease (AD) to changes in the Default Mode Network (DMN), including greater atrophy within the hippocampus (HC) as well as diminished functional connectivity and effective connectivity between anatomical DMN structures. Animal models have described the HC as a primary region of interest in studying the effects of exercise on adult neurogenesis and memory performance. Human studies have demonstrated that aerobic exercise leads to greater cardiorespiratory fitness and improved functional connectivity in the DMN for healthy adults. The goal of this study is to go beyond the predictions of human and animal studies to investigate how cardiorespiratory fitness may be used to estimate effective connectivity between the HC and the other DMN structures for young adults using resting state fMRI. Due to the data driven nature of this study, no hypothesis has been formulated. To investigate, data from 25 sedentary young adults was analyzed. Data included a resting state fMRI procedure and a cardiorespiratory fitness test, each taken from part of a larger ongoing clinical trial in the Brain Plasticity and Neuroimaging (BPN) Lab at Boston University (BU). We utilized group independent component analysis (GICA) to identify the regions that define the DMN and Conditional Granger Causality Analysis (CGCA) to determine effective connectivity between these regions. GICA indicated 9 structural regions in the DMN, consistent with previous work. This resulted in 72 possible instances of effective connectivity. The difference of causal influence between regions was calculated for each pair of DMN regions for CGCA, resulting in 36 possible instances of causal connectivity. Linear regression models were created to analyze the effect of cardiorespiratory fitness on effective connectivity between DMN regions and found 11 linear models which exhibited a significant (p > 0.05) relationship. Eight of eleven models involved the left or right hippocampus, showing that greater cardiorespiratory fitness is correlated with changes effective connectivity between the HC and the PCC, MPFC, or LTC. These results provide proof of concept that cardiorespiratory fitness in young adults is associated with changes DMN effective connectivity, particularly involving the hippocampus. This adds to the literature suggesting extended aerobic exercise, which is known to increase cardiorespiratory fitness and has been shown to increase the volume of the HC in older adults, may be neuroprotective of the HC across the lifespan. Further investigation is required to explore how effective connectivity in the DMN changes following an aerobic exercise intervention.
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