Vascular Modulation of Resting-State fMRI Functional Connectivity

Widely used in resting-state fMRI functional connectivity measurement (fcMRI), the BOLD signal is an indirect measure of neuronal activity, inherently modulated by vascular physiology. Notably, cerebrovascular reactivity (CVR) varies across individuals irrespective of neuronal changes, with unknown implications, compromising fcMRI interpretation. This work quantifies the relationship between CVR and resting motor fcMRI in healthy young adults. We modulate CVR within each individual, altering vascular tension through end-tidal CO2 (PETCO2), and measure fcMRI during hypercapnic, hypocapnic and normocapnic states. PETCO2 significantly influenced CVR and fcMRI, but with different directionalities. Resting motor fcMRI was significantly positively associated with CVR across the group, however, the CVR-fcMRI relationship was highly subject dependent. Furthermore, the relationship was not mediated by BOLD signal fluctuation amplitude. This work demonstrates and quantifies a major vascular modulator of resting fcMRI among healthy individuals. We suggest that correcting for CVR in fcMRI is important in studying healthy and diseased brains.