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

Abstract

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 CO 2 (PETCO 2 ), 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 PETCO 2 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.

Ageing and the resting state: is cognition obsolete?

“…Moreover, since functional connectivity measures reflect correlated fluctuations in the blood oxygenation level dependent (BOLD) signal, any physiological factors that are known to affect the BOLD signal will also affect measures of functional connectivity (Liu, 2013; Murphy, Birn, & Bandettini, 2013). Vascular health and neurovascular coupling are known to decline with age (D’Esposito, Deouell, & Gazzaley, 2003) and despite attempts to correct for these factors, age differences in resting state connectivity may be at least partly attributable to differences in these non-neural factors (Golestani, Kwinta, Strother, Khatamian, & Chen, 2016). Unlike rest, cognitive tasks include events of interest that can be explicitly modeled and contrasted, allowing for the decoupling of the signal of interest from that of noise and the comparison of relative differences in activation and connectivity across groups and conditions (Buckner, Snyder, Sanders, Raichle, & Morris, 2000; Henson, 2006; O’Reilly, Woolrich, Behrens, Smith, & Johansen-Berg, 2012).…”

Challenges in measuring individual differences in functional connectivity using fMRI: The case of healthy aging

“…One important issue is separating the effects of age (or any other variable) on neural versus vascular components of the fMRI signal [Murphy et al, 2013;Tsvetanov et al, 2015]. Functional connectivity estimates, for example, can be confounded by physiological rhythms, such as breathing and heart rate, and different degrees of cerebrovascular reactivity [Golestani et al, 2015[Golestani et al, , 2016Liu, 2013]. This is particularly problematic in the case of aging, given that such rhythms are known to be affected by age.…”

The efficiency of the brain connectome is associated with cerebrovascular reactivity in persons with white matter hyperintensities

“…A prior study found an association between functional connectivity based on fMRI and CVR (Golestani, Kwinta, Strother, Khatamian, & Chen, 2016). A prior study found an association between functional connectivity based on fMRI and CVR (Golestani, Kwinta, Strother, Khatamian, & Chen, 2016).…”

“…A prior study found an association between functional connectivity based on fMRI and CVR (Golestani, Kwinta, Strother, Khatamian, & Chen, 2016). It was unclear if this association was due to the spuriously altered fMRI BOLD effect related to the altered blood flow or if it was due to a true decrease in brain connectivity (Golestani et al, 2016;Para et al, 2017). An F I G U R E 4 Scatter plots comparing white matter CVR with the global efficiency and local efficiency of the connectome.…”