Altered dynamic functional connectivity in weakly-connected state in major depressive disorder

Objective: Major depressive disorder (MDD) is accompanied by abnormal changes in dynamic functional connectivity (FC) among brain regions. The aim of this study is to investigate whether the abnormalities of dynamic FC in MDD are state-dependent (related to a specific connectivity state). Methods: We performed time-varying connectivity analysis on resting-state functional magnetic resonance imaging (rs-fMRI) of 49 MDD patients and 54 matched healthy controls (HCs). FC differences between groups in each connectivity state were analyzed and associations between disease severity and dynamics of aberrant FC were explored. Results: Two distinct connectivity states (i.e., weakly-connected and strongly-connected state) were identified. Compared to HCs, MDD patients were associated with increased mean dwell time and decreased FC between and within subnetworks in the weakly-connected state. Dynamics of reduced FC between cognitive control network and default mode network as well as within cognitive control network predicted individual differences in depression symptom severity. Conclusions: Our findings suggested that the MDD-caused FC alterations mostly appeared in the weakly-connected state, which might contribute to clinical diagnosis of MDD. Significance: These findings provide new perspectives for understanding the state-dependent neurophysiological mechanisms in MDD.