Characterizing the modulation of resting-state fMRI metrics by baseline physiology

The association between resting‐state functional magnetic resonance imaging and aortic pulse‐wave velocity in healthy adults

“…By definition, increased vascular stiffness translates into reductions in vascular elasticity (Kotsis & Stabouli, ; Zavoreo & Demarin, ), hence reduced CVR and reduced BOLD signal amplitude. Such associations between CVR and the resting‐state BOLD signal have been reported previously by ourselves and others (Chu et al, ; Golestani et al, ; Kannurpatti, Motes, Biswal, & Rypma, ). Our finding of decreasing resting BOLD signal variance with increasing PWV is consistent with task‐based findings and supports our hypothesis the common mediator may be diminishing vascular reactivity.…”

“…As systemic (whole‐body) arterial stiffness is known to be reflected in the flow pattern of major cerebral arteries (Xu et al, ), we used cardiac MRI to measure aortic PWV, which is a good approximation of carotid stiffness (Kröner et al, ; Nagai et al, ). Based on the literature outlined earlier (Chu et al, ; Golestani et al, ; Guevara et al, ; Steward et al, ), we hypothesize that (1) as arterial stiffening leads to CVR reduction, the amplitude of the BOLD signal fluctuations is inversely associated with PWV; (2) as arterial stiffening is a hallmark of aging, these fMRI‐related associations are similar to the effect of age; (3) as arterial stiffening is associated with CBF and CVR reduction, BOLD‐based functional connectivity is inversely associated with PWV. Furthermore, we investigate the roles of (systemic) blood pressure and contribution of local cerebral blood flow in these relationships.…”

“…The role of vascular stiffness as a risk factor for age‐related cognitive deficits is being actively investigated (Scuteri, Brancati, Gianni, Assisi, & Volpe, ; Tarumi et al, ; Tsao et al, ). As mentioned earlier, arterial stiffness could simultaneously affect CBF, CVR, and blood pressure, all of which are known to affect the fMRI signal, during tasks and in resting state (Chu et al, ; Golestani et al, ; Liu, ; Wang et al, ). However, there has been very limited research into the relationship between vascular stiffness and imaging‐based “functional” measures, particularly those obtained using rs‐fMRI.…”

“…Although it is intuitive to attribute the effects in IC solely to those in BOLD‐fluctuation amplitude, this reasoning is not supported by the data (Figure ). In fact, the relationship between correlation‐based functional connectivity and BOLD‐signal amplitude is rather complex (Chu et al, ). Our previous work shows that, reductions in CVR (in this case a common result of arterial stiffening) will be reflected in reduced BOLD‐signal variance but not necessarily into reduced functional correlations, as the latter is also dependent on basal CBF.…”

“…However, resting‐state fMRI (rs‐fMRI) has been more widely used in studying brain function, particularly dominating the study of cognitive aging. The rs‐fMRI signal fluctuation amplitude and corresponding functional connectivity are both driven by vascular factors including cerebrovascular reactivity (CVR) and cerebral blood flow (CBF) (Chu, Golestani, Kwinta, Khatamian, & Chen, ; Golestani, Kwinta, Strother, Khatamian, & Chen, ). Moreover, it is well documented that both the amplitude of the BOLD response (Ances et al, ) and the variance of resting‐state BOLD signal decrease with increasing age (Grady & Garrett, ).…”