Aberrant functional metastability and structural connectivity are associated with rumination in individuals with major depressive disorder

Rumination is a repetitive and compulsive thinking focusing on oneself, and the nature and consequences of distress. It is a core characteristic in psychiatric disorders characterized by affective dysregulation, and emerging evidence suggests that rumination is associated with aberrant dynamic functional connectivity and structural connectivity. However, the underlying neural mechanisms remain poorly understood. Here, we adopted a multimodal approach and tested the hypothesis that white matter connectivity forms the basis of the implications of temporal dynamics of functional connectivity in the rumination trait. Fifty-three depressed and ruminative individuals and a control group of 47 age- and gender-matched individuals with low levels of rumination underwent resting-state fMRI and diffusion tensor imaging. We found that lower global metastability and higher global synchrony of the dynamic functional connectivity were associated with higher levels of rumination. Specifically, the altered global synchrony and global metastability mediated the association between white matter integrity of the genu of the corpus callosum to rumination. Hence, our findings offered the first line of evidence for the intricate role of (sub)optimal transition of functional brain states in the connection of structural brain connectivity in ruminative thinking. Copyright © 2021 The Author(s). Published by Elsevier Inc.