Functional connectivity profiles in remitted depression and their relation to ruminative thinking

The triple network model suggests that dysfunction in three major brain networks - the default mode network (DMN), central executive network (CEN), and salience network (SN) - might contribute to cognitive impairments in various psychiatric disorders, including major depressive disorder (MDD). While hyperconnectivity in the DMN, hypoconnectivity in the CEN, and abnormal SN connectivity have been observed in acutely depressed patients, evidence for network alterations during remission is limited. Further, there are few studies examining connectivity in people in remission from MDD (rMDD) during emotional processing tasks, including during affective cognition (i.e., tasks that encompass affective processing in the context of cognitive processes, such as inhibition). To address these literature gaps, this study compared functional connectivity (FC) between resting and task conditions, specifically during the emotional Stroop (eStroop) task, as well as between rMDD and healthy volunteers (HVs), within and between nodes of the three networks. We also explored how FC relates to rumination in the rMDD group, given that rumination tends to persist in rMDD and involves affective and cognitive networks. We unexpectedly found greater FC during the task vs. rest condition within the DMN, and decreased FC during the task vs. rest conditions within the CEN and SN across the groups. Greater FC during the task vs. rest condition between DMN and SN nodes, as well as between CEN and SN nodes were also observed. These effects were more pronounced in the rMDD group as per our exploratory analyses. Additionally, the rMDD vs. HV group showed higher FC between DMN-CEN nodes, regardless of condition. Higher hopeless rumination scores were associated with decreased resting FC within the DMN, while higher active problem-solving scores were associated with increased task FC within the DMN in the rMDD group. These findings suggest that tasks engaging affective cognition processes influence FC within and among the three networks, with this effect more pronounced in the rMDD group. This might indicate potential protective and compensatory mechanisms in rMDD and expands our understanding of large-scale intrinsic network connectivity alterations during remission from depression. However, given the limited sample and the exploratory nature of some of our analyses, replication is necessary.