On the nature of time-varying functional connectivity in resting fMRI

The brain is a complex dynamical system composed of many interacting sub-regions. Knowledge of how these interactions reconfigure over time is critical to a full understanding of the brain’s functional architecture, the neural basis of flexible cognition and behavior, and how neural systems are disrupted in psychiatric and neurological illness. The idea that we might be able to study neural and cognitive dynamics through analysis of neuroimaging data has catalyzed substantial interest in methods which seek to estimate moment-to-moment fluctuations in functional connectivity (often referred to as “dynamic” or time-varying connectivity; TVC). At the same time, debates have emerged regarding the application of TVC analyses to resting fMRI data, and about the statistical validity, physiological origins, and cognitive relevance of resting TVC. These and other unresolved issues complicate the interpretation of resting TVC findings and limit the insights which can be gained from this otherwise promising research area. This article reviews the current resting TVC literature in light of these issues. We introduce core concepts, define key terms, summarize current controversies and open questions, and present a forward-looking perspective on how resting TVC analyses can be rigorously applied to investigate a wide range of questions in cognitive and systems neuroscience.