Author Summary We tested the replicability and generalizability of a previously proposed negative association between dynamic brain network reconfigurations derived from multilayer modularity detection (node flexibility) and psychological resilience. Using multiband resting-state BOLD fMRI data and exploring several parcellation schemes, sliding window approaches, and temporal resolutions of the data, we could not replicate previously reported findings regarding the association between node flexibility and resilience. By extending this work to other measures of brain dynamics (node promiscuity, degree) we observe a rather inconsistent pattern of correlations with resilience that strongly varies across analysis choices. We conclude that further research is needed to understand the network neuroscience basis of mental health and discuss several reasons that may account for the variability in results. Abstract This study aimed at replicating a previously reported negative correlation between node flexibility and psychological resilience, that is, the ability to retain mental health in the face of stress and adversity. To this end, we used multiband resting-state BOLD fMRI (TR = .675 sec) from 52 participants who had filled out three psychological questionnaires assessing resilience. Time-resolved functional connectivity was calculated by performing a sliding window approach on averaged time series parcellated according to different established atlases. Multilayer modularity detection was performed to track network reconfigurations over time, and node flexibility was calculated as the number of times a node changes community assignment. In addition, node promiscuity (the fraction of communities a node participates in) and node degree (as proxy for time-varying connectivity) were calculated to extend previous work. We found no substantial correlations between resilience and node flexibility. We observed a small number of correlations between the two other brain measures and resilience scores that were, however, very inconsistently distributed across brain measures, differences in temporal sampling, and parcellation schemes. This heterogeneity calls into question the existence of previously postulated associations between resilience and brain network flexibility and highlights how results may be influenced by specific analysis choices.

The brain is a complex, multiscale dynamical system composed of many interacting regions. Knowledge of the spatiotemporal organization of these interactions is critical for establishing a solid understanding of the brain’s functional architecture and the relationship between neural dynamics and cognition in health and disease. The possibility of studying these dynamics through careful analysis of neuroimaging data has catalyzed substantial interest in methods that estimate time-resolved fluctuations in functional connectivity (often referred to as “dynamic” or time-varying functional connectivity; TVFC). At the same time, debates have emerged regarding the application of TVFC analyses to resting fMRI data, and about the statistical validity, physiological origins, and cognitive and behavioral relevance of resting TVFC. These and other unresolved issues complicate interpretation of resting TVFC findings and limit the insights that can be gained from this promising new research area. This article brings together scientists with a variety of perspectives on resting TVFC to review the current literature in light of these issues. We introduce core concepts, define key terms, summarize controversies and open questions, and present a forward-looking perspective on how resting TVFC analyses can be rigorously and productively applied to investigate a wide range of questions in cognitive and systems neuroscience.