Resting-state functional magnetic resonance imaging (rs-fMRI) is frequently used to study brain function; but, it is unclear whether BOLD-signal fluctuation amplitude and functional connectivity are associated with vascular factors, and how vascular-health factors are reflected in rs-fMRI metrics in the healthy population. As arterial stiffening is a known age-related cardiovascular risk factor, we investigated the associations between aortic stiffening (as measured using pulse-wave velocity [PWV]) and rs-fMRI metrics. We used cardiac MRI to measure aortic PWV (an established indicator of whole-body vascular stiffness), as well as dual-echo pseudo-continuous arterial-spin labeling to measure BOLD and CBF dynamics simultaneously in a group of generally healthy adults. We found that: (1) higher aortic PWV is associated with lower variance in the resting-state BOLD signal; (2) higher PWV is also associated with lower BOLD-based resting-state functional connectivity; (3) regions showing lower connectivity do not fully overlap with those showing lower BOLD variance with higher PWV; (4) CBF signal variance is a significant mediator of the above findings, only when averaged across regions-of-interest. Furthermore, we found no significant association between BOLD signal variance and systolic blood pressure, which is also a known predictor of vascular stiffness. Age-related vascular stiffness, as measured by PWV, provides a unique scenario to demonstrate the extent of vascular bias in rs-fMRI signal fluctuations and functional connectivity. These findings suggest that a substantial portion of age-related rs-fMRI differences may be driven by vascular effects rather than directly by brain function.
Keywords: BOLD signal amplitude; aging; aortic stiffness; arterial stiffening; blood pressure; blood-oxygenation level dependent signal (BOLD); functional MRI (fMRI); functional connectivity; phase-contrast imaging; pulse wave velocity; resting-state fMRI.
© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.