Brain effective connectivity and functional connectivity as markers of lifespan vascular exposures in middle-aged adults: The Bogalusa Heart Study

Introduction: Effective connectivity (EC), the causal influence that functional activity in a source brain location exerts over functional activity in a target brain location, has the potential to provide different information about brain network dynamics than functional connectivity (FC), which quantifies activity synchrony between locations. However, head-to-head comparisons between EC and FC from either task-based or resting-state functional MRI (fMRI) data are rare, especially in terms of how they associate with salient aspects of brain health.

Methods: In this study, 100 cognitively-healthy participants in the Bogalusa Heart Study aged 54.2 ± 4.3years completed Stroop task-based fMRI, resting-state fMRI. EC and FC among 24 regions of interest (ROIs) previously identified as involved in Stroop task execution (EC-task and FC-task) and among 33 default mode network ROIs (EC-rest and FC-rest) were calculated from task-based and resting-state fMRI using deep stacking networks and Pearson correlation. The EC and FC measures were thresholded to generate directed and undirected graphs, from which standard graph metrics were calculated. Linear regression models related graph metrics to demographic, cardiometabolic risk factors, and cognitive function measures.

Results: Women and whites (compared to men and African Americans) had better EC-task metrics, and better EC-task metrics associated with lower blood pressure, white matter hyperintensity volume, and higher vocabulary score (maximum value of p = 0.043). Women had better FC-task metrics, and better FC-task metrics associated with APOE-ε4 3–3 genotype and better hemoglobin-A1c, white matter hyperintensity volume and digit span backwards score (maximum value of p = 0.047). Better EC rest metrics associated with lower age, non-drinker status, and better BMI, white matter hyperintensity volume, logical memory II total score, and word reading score (maximum value of p = 0.044). Women and non-drinkers had better FC-rest metrics (value of p = 0.004).

Discussion: In a diverse, cognitively healthy, middle-aged community sample, EC and FC based graph metrics from task-based fMRI data, and EC based graph metrics from resting-state fMRI data, were associated with recognized indicators of brain health in differing ways. Future studies of brain health should consider taking both task-based and resting-state fMRI scans and measuring both EC and FC analyses to get a more complete picture of functional networks relevant to brain health.