The default mode network and self-referential processes in depression

TLDR

The default mode network (DMN) is a self‑referential brain network whose structure and function are altered in major depression, implicating it in the disorder’s disturbed self‑referential thought. This study aimed to determine whether patients with major depression exhibit impaired regulation of DMN activity during self‑referential processing. Participants, including patients and controls, viewed negative images passively and then actively reappraised them while their brain activity was recorded. Depressed subjects failed to down‑regulate DMN activity during both passive viewing and reappraisal, showed exaggerated activation of amygdala, parahippocampus, and hippocampus, and overall displayed heightened stimulus‑induced DMN activity, supporting a network basis for depression.

Abstract

The recently discovered default mode network (DMN) is a group of areas in the human brain characterized, collectively, by functions of a self-referential nature. In normal individuals, activity in the DMN is reduced during nonself-referential goal-directed tasks, in keeping with the folk-psychological notion of losing one's self in one's work. Imaging and anatomical studies in major depression have found alterations in both the structure and function in some regions that belong to the DMN, thus, suggesting a basis for the disordered self-referential thought of depression. Here, we sought to examine DMN functionality as a network in patients with major depression, asking whether the ability to regulate its activity and, hence, its role in self-referential processing, was impaired. To do so, we asked patients and controls to examine negative pictures passively and also to reappraise them actively. In widely distributed elements of the DMN [ventromedial prefrontal cortex prefrontal cortex (BA 10), anterior cingulate (BA 24/32), lateral parietal cortex (BA 39), and lateral temporal cortex (BA 21)], depressed, but not control subjects, exhibited a failure to reduce activity while both looking at negative pictures and reappraising them. Furthermore, looking at negative pictures elicited a significantly greater increase in activity in other DMN regions (amygdala, parahippocampus, and hippocampus) in depressed than in control subjects. These data suggest depression is characterized by both stimulus-induced heightened activity and a failure to normally down-regulate activity broadly within the DMN. These findings provide a brain network framework within which to consider the pathophysiology of depression.