The Default Mode Network and Self-Referential Processes in Depression

Department of Psychiatry, Washington University, St. Louis, MO 63110, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/2009; 106(6):1942-7. DOI: 10.1073/pnas.0812686106
Source: PubMed

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.

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Available from: Rebecca S Coalson, Sep 28, 2015
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    • "ion in the PFC and hippocampus ( Sheline et al . , 2001 ; Davidson et al . , 2003 ) . It has been postulated that depression may be caused by failures of cognitive processing and emotional regulation systems ( Mayberg , 1997 ) . Supporting this view , depressed people have been observed to exhibit a failure to down - regulate activities normally ( Sheline et al . , 2009 ) ."
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    ABSTRACT: Previous studies have focused on resting-state default mode network (DMN) alterations in the development and maintenance of depression; however, only a few studies have addressed DMN changes during task-related processing and their results are inconsistent. Therefore, we explored DMN patterns in young adult patients with first-episode, treatment-naïve major depressive disorder (MDD) performing an implicit emotional processing task. Patients with MDD (N = 29) and healthy controls (N = 33) were subjected to functional magnetic resonance imaging (fMRI) at rest and while performing a gender judgment task. Group independent component analysis (ICA) was used to identify DMN component under task state for both groups. The DMN of participants with MDD had decreased functional connectivity in bilateral prefrontal areas compared to controls. Right prefrontal gyrus connectivity for MDD patients correlated negatively with scores on maladaptive scales of the Cognitive Emotion Regulation Questionnaire (CERQ). Our findings suggest that depressed people have altered DMN patterns during implicit emotional processing, which might be related to impaired internal monitoring and emotional regulation ability.
    Frontiers in Psychology 08/2015; 6:1198. DOI:10.3389/fpsyg.2015.01198 · 2.80 Impact Factor
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    • "Serotonergic modulation affected the cingulate, orbitofrontal and parietal and temporal association cortices which is consistent with studies in human subjects demonstrating the involvement of 5HT1A receptors in the regulation of the DMN (Hahn et al. 2012). The role of the DMN in memory processes and emotional behavior could be mediated through serotonergic receptors, deficits of which lead to DMN FC disruptions in, e.g., depression and autism disorders (Sheline et al. 2009; Washington et al. 2014). Similar FC disruptions were induced in the DMN-like network by cholinergic and serotonergic modulations, with the exception of the additional involvement of the retrosplenial cortex after cholinergic modulation. "
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    ABSTRACT: Resting-state functional MRI (rsfMRI) is a widely implemented technique used to investigate large-scale topology in the human brain during health and disease. Studies in mice provide additional advantages, including the possibility to flexibly modulate the brain by pharmacological or genetic manipulations in combination with high-throughput functional connectivity (FC) investigations. Pharmacological modulations that target specific neurotransmitter systems, partly mimicking the effect of pathological events, could allow discriminating the effect of specific systems on functional network disruptions. The current study investigated the effect of cholinergic and serotonergic antagonists on large-scale brain networks in mice. The cholinergic system is involved in cognitive functions and is impaired in, e.g., Alzheimer's disease, while the serotonergic system is involved in emotional and introspective functions and is impaired in, e.g., Alzheimer's disease, depression and autism. Specific interest goes to the default-mode-network (DMN), which is studied extensively in humans and is affected in many neurological disorders. The results show that both cholinergic and serotonergic antagonists impaired the mouse DMN-like network similarly, except that cholinergic modulation additionally affected the retrosplenial cortex. This suggests that both neurotransmitter systems are involved in maintaining integrity of FC within the DMN-like network in mice. Cholinergic and serotonergic modulations also affected other functional networks, however, serotonergic modulation impaired the frontal and thalamus networks more extensively. In conclusion, this study demonstrates the utility of pharmacological rsfMRI in animal models to provide insights into the role of specific neurotransmitter systems on functional networks in neurological disorders.
    Brain Structure and Function 07/2015; DOI:10.1007/s00429-015-1087-7 · 5.62 Impact Factor
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    • "rt of self - related brain area called the cortical midline structure ( CMS ; Northoff and Bermpohl , 2004 ; Heatherton et al . , 2006 ) . This region also has been known to be one of important part of the default mode network ( DMN ) that is indicated to relate internal self - related processing ( Gusnard et al . , 2001 ; Buckner et al . , 2008 ; Sheline et al . , 2009 ; Spreng and Grady , 2010 ; Salomon et al . , 2014 ) . Kelley et al . ( 2002 ) and Yoshimura et al . ( 2009 ) used the above mentioned trait - adjective judgment task in an fMRI study to demonstrate that VMPFC was selectively FIGURE 3 | Significantly activated regions distinguished by measuring the contrast between self_correct and othe"
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    ABSTRACT: The self-reference effect (SRE) is defined as better recall or recognition performance when the memorized materials refer to the self. Recently, a number of neuroimaging studies using self-referential and other-referential tasks have reported that self- and other-referential judgments basically show greater activation in common brain regions, specifically in the medial prefrontal cortex (MPFC) when compared with nonmentalizing judgments, but that a ventral-to-dorsal gradient in MPFC emerges from a direct comparison between self- and other-judgments. However, most of these previous studies could not provide an adequate explanation for the neural basis of SRE because they did not directly compare brain activation for recognition/recall of the words referenced to the self with another person. Here, we used an event-related functional magnetic resonance imaging (fMRI) that measured brain activity during processing of references to the self and another, and for recognition of self and other referenced words. Results from the fMRI evaluation task indicated greater activation in ventromedial prefrontal cortex (VMPFC) in the self-referential condition. While in the recognition task, VMPFC, posterior cingulate cortex (PCC) and bilateral angular gyrus (AG) showed greater activation when participants correctly recognized self-referenced words versus other-referenced words. These data provide evidence that the self-referenced words evoked greater activation in the self-related region (VMPFC) and memory-related regions (PCC and AG) relative to another person in the retrieval phase, and that the words remained as a stronger memory trace that supports recognition.
    Frontiers in Human Neuroscience 06/2015; 9:383. DOI:10.3389/fnhum.2015.00383 · 2.99 Impact Factor
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