Abstract

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.

Highlights

  • Arterial stiffening is associated with higher risk for stroke and cardiovascular disease (Gavish & Izzo, 2016)

  • Steward et al showed that pulse wave velocity (PWV) is negatively correlated with the amplitude of the blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging response measured in a working-memory task in healthy middle-aged individuals (Steward et al, 2014)

  • In our sample of healthy young to middleaged adults, we find that: (1) there is a significant negative association between PWV and Resting-state functional magnetic resonance imaging (rs-functional MRI (fMRI)) low-frequency blood-oxygenation level dependent signal (BOLD) fMRI signal amplitude; (2) these associations are spatially distinct from the effect of age on resting-BOLD signal ampoitude; (3) PWV is negatively associated with resting-state functional connectivity

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Summary

| INTRODUCTION

Arterial stiffening is associated with higher risk for stroke and cardiovascular disease (Gavish & Izzo, 2016). A healthy aorta (and carotid artery) acts as an elastic buffer and converts the systolic inflow into a smoother, continuous outflow to the brain (and other organs) This so-called “Windkessel effect” is impared in stiff arteries (Belz, 1995), leading to increased pulsatile flow at the brain, which is a potential risk factor of cerebral small-vessel damage. Steward et al showed that PWV is negatively correlated with the amplitude of the blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) response measured in a working-memory task in healthy middle-aged individuals (Steward et al, 2014) This provided the first evidence of the impact of arterial stiffening on the BOLD task response. We investigate the roles of (systemic) blood pressure and contribution of local cerebral blood flow in these relationships

| Participants and anthropometric assessments
| RESULTS
| DISCUSSION
| Limitations
Findings
| CONCLUSION
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