default mode network and self-referential processes in depression

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 6; pp. 1942 - 1947
• Main Authors: Sheline, Yvette I, Barch, Deanna M, Price, Joseph L, Rundle, Melissa M, Vaishnavi, S. Neil, Snyder, Abraham Z, Mintun, Mark A, Wang, Suzhi, Coalson, Rebecca S, Raichle, Marcus E
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 10.02.2009; National Acad Sciences
• Subjects: Adult; Amygdala; Anatomy; Behavior; Behavioral neuroscience; Biological Sciences; Brain; Brain Mapping; Case-Control Studies; Cerebral Cortex; Cognition & reasoning; Connected regions; Depressive Disorder, Major - physiopathology; Depressive disorders; Ego; Emotional expression; Emotions; Female; Humans; Limbic System; Magnetic resonance imaging; Major depressive disorder; Male; Mental depression; Neurological disorders; Physiological regulation; Physiology; Prefrontal Cortex; Visual Perception; Young Adult
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0812686106

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.