Resting-State fMRI: Emerging Concepts for Future Clinical Application

Resting-state functional magnetic resonance imaging (rsfMRI) has been developed as a method of investigating spontaneous neural activity. Based on its low-frequency signal synchronization, rsfMRI has made it possible to identify multiple macroscopic structures termed resting-state networks (RSNs) on a single scan of less than 10 minutes. It is easy to implement even in clinical practice, in which assigning tasks to patients can be challenging. These advantages have accelerated the adoption and growth of rsfMRI. Recently, studies on the global rsfMRI signal have attracted increasing attention. Because it primarily arises from physiological events, less attention has hitherto been paid to the global signal than to the local network (i.e., RSN) component. However, the global signal is not a mere nuisance or a subsidiary component. On the contrary, it is quantitatively the dominant component that accounts for most of the variance in the rsfMRI signal throughout the brain and provides rich information on local hemodynamics that can serve as an individual-level diagnostic biomarker. Moreover, spatiotemporal analyses of the global signal have revealed that it is closely and fundamentally associated with the organization of RSNs, thus challenging the basic assumptions made in conventional rsfMRI analyses and views on RSNs. This review introduces new concepts emerging from rsfMRI spatiotemporal analyses focusing on the global signal and discusses how they may contribute to future clinical medicine. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 1.