It is widely known that blood oxygenation level dependent (BOLD) contrast in functional magnetic resonance imaging (fMRI) is an indirect measure for neuronal activations through neurovascular coupling. The BOLD signal is also influenced by many non-neuronal physiological fluctuations. In previous resting state (RS) fMRI studies, we have identified a moving systemic low frequency oscillation (sLFO) in BOLD signal and were able to track its passage through the brain. We hypothesized that this seemingly intrinsic signal moves with the blood, and therefore, its dynamic patterns represent cerebral blood flow. In this study, we tested this hypothesis by performing Dynamic Susceptibility Contrast (DSC) MRI scans (i.e. bolus tracking) following the RS scans on eight healthy subjects. The dynamic patterns of sLFO derived from RS data were compared with the bolus flow visually and quantitatively. We found that the flow of sLFO derived from RS fMRI does to a large extent represent the blood flow measured with DSC. The small differences, we hypothesize, are largely due to the difference between the methods in their sensitivity to different vessel types. We conclude that the flow of sLFO in RS visualized by our time delay method represents the blood flow in the capillaries and veins in the brain.
Resting state functional connectivity analysis is a widely used method for mapping intrinsic functional organization of the brain. Global signal regression (GSR) is commonly employed for removing systemic global variance from resting state BOLD-fMRI data; however, recent studies have demonstrated that GSR may introduce spurious negative correlations within and between functional networks, calling into question the meaning of anticorrelations reported between some networks. In the present study, we propose that global signal from resting state fMRI is composed primarily of systemic low frequency oscillations (sLFOs) that propagate with cerebral blood circulation throughout the brain. We introduce a novel systemic noise removal strategy for resting state fMRI data, "dynamic global signal regression" (dGSR), which applies a voxel-specific optimal time delay to the global signal prior to regression from voxel-wise time series. We test our hypothesis on two functional systems that are suggested to be intrinsically organized into anticorrelated networks: the default mode network (DMN) and task positive network (TPN). We evaluate the efficacy of dGSR and compare its performance with the conventional "static" global regression (sGSR) method in terms of (i) explaining systemic variance in the data and (ii) enhancing specificity and sensitivity of functional connectivity measures. dGSR increases the amount of BOLD signal variance being modeled and removed relative to sGSR while reducing spurious negative correlations introduced in reference regions by sGSR, and attenuating inflated positive connectivity measures. We conclude that incorporating time delay information for sLFOs into global noise removal strategies is of crucial importance for optimal noise removal from resting state functional connectivity maps.
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