The subsystem mechanism of default mode network underlying rumination: A reproducible neuroimaging study.

Rumination is a repetitive self-referential thinking style that is often interpreted as an expression of abnormalities of the default mode network (DMN) observed during "resting-state" in major depressive disorder (MDD). Recent evidence has demonstrated that the DMN is not unitary but can be further divided into 3 functionally heterogenous subsystems, although the subsystem mechanistically underlying rumination remains unclear. Due to the unconstrained and indirect correlational nature of previous resting-state fMRI studies on rumination's network underpinnings, a paradigm allowing direct investigation of network interactions during active rumination is needed. Here, with a modified continuous state-like paradigm, we induced healthy participants to ruminate or imagine objective scenarios (distraction, as a control condition) on 3 different MRI scanners. We compared functional connectivities (FC) of the DMN and its 3 subsystems between rumination and distraction states. Results yielded a highly reproducible and dissociated pattern. During rumination, within-DMN FC was generally decreased as compared to the distraction state. At the subsystem level, we found increased FC between the core and medial temporal lobe (MTL) subsystem as well as decreased FC between the core and dorsal medial prefrontal cortex (DMPFC) subsystem and within the MTL subsystem. Finally, subjects' behavioral measures of rumination and brooding were negatively correlated with FC between the core and DMPFC subsystems. These results suggest active rumination involves enhanced constraint by the core subsystem on the MTL subsystem and decreased coupling between the core and DMPFC subsystem, allowing for more information exchange among those involved DMN components. Furthermore, the reproducibility of our findings provides a rigorous evaluation of their validity and significance.

Rumination and the default mode network: Meta-analysis of brain imaging studies and implications for depression.

Rumination is strongly and consistently correlated with depression. Although multiple studies have explored the neural correlates of rumination, findings have been inconsistent and the mechanisms underlying rumination remain elusive. Functional brain imaging studies have identified areas in the default mode network (DMN) that appear to be critically involved in ruminative processes. However, a meta-analysis to synthesize the findings of brain regions underlying rumination is currently lacking. Here, we conducted a meta-analysis consisting of experimental tasks that investigate rumination by using Signed Differential Mapping of 14 fMRI studies comprising 286 healthy participants. Furthermore, rather than treat the DMN as a unitary network, we examined the contribution of three DMN subsystems to rumination. Results confirm the suspected association between rumination and DMN activation, specifically implicating the DMN core regions and the dorsal medial prefrontal cortex subsystem. Based on these findings, we suggest a hypothesis of how DMN regions support rumination and present the implications of this model for treating major depressive disorder characterized by rumination.