The association between cerebrovascular reactivity and resting-state fMRI functional connectivity in healthy adults: The influence of basal carbon dioxide

• Published in: NeuroImage (Orlando, Fla.) Fla.), 2016-05, Vol.132, p.301-313
• Main Authors: Golestani, Ali M., Kwinta, Jonathan B., Strother, Stephen C., Khatamian, Yasha B., Chen, J. Jean
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Amplitude of low-frequency fluctuations (ALFF); Brain - blood supply; Brain - metabolism; Brain - physiology; Brain Mapping; Brain research; Carbon Dioxide - metabolism; Cerebrovascular reactivity (CVR); Colleges & universities; Conflicts of interest; End-tidal CO2 (PETCO2); Female; Heart rate; Humans; Magnetic Resonance Imaging; Male; Motor Cortex - physiology; Neural Pathways - physiology; NMR; Nuclear magnetic resonance; Physiology; Respiration; Resting-state BOLD fMRI (rs-fMRI); Resting-state functional connectivity (fcMRI); Seeds; Vascular tension; Young Adult
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2016.02.051

Although widely used in resting-state fMRI (fMRI) functional connectivity measurement (fcMRI), the BOLD signal is only an indirect measure of neuronal activity, and is inherently modulated by both neuronal activity and vascular physiology. For instance, cerebrovascular reactivity (CVR) varies widely across individuals irrespective of neuronal function, but the implications for fcMRI are currently unknown. This knowledge gap compromises our ability to correctly interpret fcMRI measurements. In this work, we investigate the relationship between CVR and resting fcMRI measurements in healthy young adults, in both the motor and the executive-control networks. We modulate CVR within each individual by subtly increasing and decreasing resting vascular tension through baseline end-tidal CO2 (PETCO2), and measure fcMRI during these hypercapnic, hypocapnic and normocapnic states. Furthermore, we assess the association between CVR and fcMRI within and across individuals. Within individuals, resting PETCO2 is found to significantly influence both CVR and resting fcMRI values. In addition, we find resting fcMRI to be significantly and positively associated with CVR across the group in both networks. This relationship is potentially mediated by concomitant alterations in BOLD signal fluctuation amplitude. This work clearly demonstrates and quantifies a major vascular modulator of resting fcMRI, one that is also subject and regional dependent. We suggest that individualized correction for CVR effects in fcMRI measurements is essential for fcMRI studies of healthy brains, and can be even more important in studying diseased brains. •Demonstrates the influence of cerebrovascular reactivity (CVR) on rs-fMRI functional connectivity (rs-fcMRI) measurements.•This CVR influence varies by subject and by brain region.•CVR likely influences rs-fMRI signal fluctuation amplitude, which in turn influences fcMRI measurements.•The CVR effect is distinct from the effect of CO2 on fcMRI measurements.•Individualized and regional-specific CVR correction is highly recommended.