Altered Dynamic Functional Connectivity of the Frontoparietal Network in Major Depressive Disorder: Evidence for Hypoconnectivity and Reduced State Transitions
Major depressive disorder (MDD) is associated with cognitive inflexibility and impaired executive function, yet the underlying network-level dynamics related to connectivity patterns remain poorly characterized. Prior research on the frontoparietal control network (FPN), a hub of cognitive regulation, has yielded inconsistent findings, often relying on static connectivity models that overlook temporally evolving architecture of the brain. Here, we leverage resting-state fMRI (rs-fMRI) data from a large, harmonized multisite dataset (n = 887; 442 MDD, 445 controls) to examine the dynamic functional connectivity (dFC) of the FPN. Using a sliding-window approach and k-means clustering, we identified three recurring FPN connectivity states. Compared to controls, patients with MDD spent significantly more time in a hypoconnected state, exhibited prolonged dwell within this configuration, and showed a global reduction in the number of transitions between network states, reflecting diminished neural flexibility. Critically, transitions between hypoconnected and hyperconnected states were selectively impaired, suggesting disrupted efficient access to functionally distinct network modes. These results demonstrate that MDD is characterized not only by altered connectivity strength but by a constricted repertoire of dynamic brain states. This temporal dysregulation of the FPN may constitute a network-level mechanism underlying cognitive inflexibility in depression, highlighting dFC as a promising modality for mechanistic insight and translational applications.