The default mode network and self-referential processes in 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.cognitive reappraisal ͉ fMRI ͉ medial prefrontal network ͉ emotional dysregulation ͉ activation differences W hen we engage in almost any goal-directed behavior of a nonself-referential nature, certain areas of the brain decrease their activity (1) when compared with a quiet resting state (e.g., awake with eyes closed). The consistency with which certain areas of the brain do so, regardless of the nature of the goal-directed task, led to the notion of an organized default mode of brain function (2) in which some regions are most active when we are in a resting state. The areas of the brain most consistently displaying such behavior regardless of task have come to be known as the default mode network (DMN) (3, 4), which consists of areas in dorsal and ventral medial prefrontal cortices, medial and lateral parietal cortex, and parts of the medial and lateral temporal cortices.Recently summarized data (4) indicate that the DMN is involved in the evaluation of potentially survival-salient information from the body and the world: perspective taking of the desires, beliefs, and intentions of others and in remembering the past as well as planning the future (2-4). All of these putative functions are self-referential in nature. Reduction of activity in the DMN during effortful cognitive processing (1, 5) can be interpreted as re...

Resting-State Connectivity Predictors of Response to Psychotherapy in Major Depressive Disorder

“…Sheline et al (2010) reported hyperconnectivity with bilateral dorsal medial prefrontal cortex across the ECN, the DMN, and the DAN and proposed that these patterns of hyperconnectivity may explain impaired concentration (ECN), increased rumination, selffocus, and vigilance (DMN), and emotional, visceral, and autonomic dysregulation (DAN) in MDD. These findings converge with other reports of aberrant affective network activation at rest and during emotional tasks in MDD (Johansen-Berg et al, 2008;Mayberg et al, 1999;Smoski et al, 2009), DMN hyperactivation during emotional tasks (Sheline et al, 2009), DMN hyperconnectivity at rest in MDD (Lemogne et al, 2009), and increased task-related connectivity (Schlosser et al, 2008;Vasic et al, 2009) and decreased task-related activation (Davidson et al, 2002;Panksepp, 2010) in the ECN in MDD.…”

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct‐disordered juvenile offenders

“…Though the CMA is not part of the canonical DMN, it is in close contact with core DMN regions (both functionally and structurally) [Bienkowski and Rinaman, 2013; Bzdok et al, 2013; Keifer et al, 2015; Pessoa, 2011; Sah et al, 2003], and may as such impact its network function. In fact, amygdalar interactions with frontal and parietal DMN nodes reported here are deemed crucial for representing and regulating socioemotional states [Fang et al, 2013; Li et al, 2014; Lieberman, 2007; Sheline et al, 2009], allowing affective coloring of core DMN functions such as self‐other distinction, theory of mind, and internal reflection [Andrews‐Hanna, 2012; Li et al, 2014; Lieberman, 2007; Shaw et al, 2004]. …”

Depression alters “top-down” visual attention: A dynamic causal modeling comparison between depressed and healthy subjects

“…Overall studies assessing connectivity (either effective or not) mainly focused on fronto-cingulate (Anand et al, 2005;Schlosser et al, 2008;Vasic et al, 2009) or fronto-amygdala connectivity (Irwin et al, 2004;Johnstone et al, 2007;Almeida et al, 2009), and pointed to a failure to down-regulate rostral anterior cingulate cortex (ACC) and amygdala responses. Several studies showed deficient downregulation within the default-mode network, including the ventromedial prefrontal and the (subgenual) anterior cingulated cortex (Greicius et al, 2007;Sheline et al, 2009). How MDD affects effective connectivity across a distributed visuo-attentional network remains unclear.…”