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


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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    • "In accord with these views, our findings suggest that higher cognitive flexibility when responding to external tasks demands may require more efficient disengagement of current self-referential processing, and that such ability might be reduced in mood disorder patients. Depression is indeed known to be characterized by a failure to deactivate regions of the DMN, including ventromedial PFC, ACC, lateral parietal cortex, and lateral temporal cortex[Sheline et al., 2009], together with extra functional connectivity of sgACC and thalamus with the DMN[Greicius et al., 2007]. A study in MDD patients reported that during a self-judgment task, ventro-medial prefrontal regions were less deactivated for patients than healthy subjects, suggesting that MDD patients might fail to downregulate their high resting state activity in sgACC because they remain " stuck in their own self "[Grimm et al., 2009;Yoshimura et al., 2010]. "
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    ABSTRACT: Impairment in mental flexibility may be a key component contributing to cardinal cognitive symptoms among mood disorders patients, particularly thought control disorders. Impaired ability to switch from one thought to another might reflect difficulties in either generating new mental states, inhibiting previous states, or both. However, the neural underpinnings of impaired cognitive flexibility in mood disorders remain largely unresolved. We compared a group of mood disorders patients (n = 29) and a group of matched healthy subjects (n = 32) on a novel task-switching paradigm involving happy and sad faces, that allowed us to separate generation of a new mental set (Switch Cost) and inhibition of the previous set during switching (Inhibition Cost), using fMRI. Behavioral data showed a larger Switch Cost in patients relative to controls, but the average Inhibition Cost did not differ between groups. At the neural level, a main effect of group was found with stronger activation of the subgenual cingulate cortex in patients. The larger Switch Cost in patients was reflected by a stronger recruitment of brain regions involved in attention and executive control, including the left intraparietal sulcus, precuneus, left inferior fontal gyrus, and right anterior cingulate. Critically, activity in the subgenual cingulate cortex was not downregulated by inhibition in patients relative to controls. In conclusion, mood disorder patients have exaggerated Switch Cost relative to controls, and this deficit in cognitive flexibility is associated with increased activation of the fronto-parietal attention networks, combined with impaired modulation of the subgenual cingulate cortex when inhibition of previous mental states is needed. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.
    No preview · Article · Jan 2016 · Human Brain Mapping
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    • "The CMS include the dorsal-and ventral-medial prefrontal cortices (MPFC) and cingulate cortex, [33] [34]. Recent meta-analyses [35] [36] and fMRI studies [37] [38] have also demonstrated that the processing of self-related and familiar contexts is associated with activity in the CMS regions, including the MPFC, PCC and anterior cingulate cortex (ACC). However, some studies have shown that in certain instances, activity in the posterior medial cortices (PMC) in the CMS was not stronger in " self " conditions compared to " others " conditions; more specifically, the region showed significantly stronger activity in the distant-others condition compared to the self condition in general [36] [37]. "
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    ABSTRACT: The present study aims to examine the relationship between the cortical midline structures (CMS), which have been regarded to be associated with selfhood, and moral decision making processes at the neural level. Traditional moral psychological studies have suggested the role of moral self as the moderator of moral cognition, so activity of moral self would present at the neural level. The present study examined the interaction between the CMS and other moral-related regions by conducting psycho-physiological interaction analysis of functional images acquired while 16 subjects were solving moral dilemmas. Furthermore, we performed Granger causality analysis to demonstrate the direction of influences between activities in the regions in moral decision-making. We first demonstrate there are significant positive interactions between two central CMS seed regions—i.e., the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC)—and brain regions associated with moral functioning including the cerebellum, brainstem, midbrain, dorsolateral prefrontal cortex, orbitofrontal cortex and anterior insula (AI); on the other hand, the posterior insula (PI) showed significant negative interaction with the seed regions. Second, several significant Granger causality was found from CMS to insula regions particularly under the moral-personal condition. Furthermore, significant dominant influence from the AI to PI was reported. Moral psychological implications of these findings are discussed. The present study demonstrated the significant interaction and influence between the CMS and morality-related regions while subject were solving moral dilemmas. Given that, activity in the CMS is significantly involved in human moral functioning.
    Full-text · Article · Jan 2016 · Behavioural Brain Research
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    • "Abnormal anatomical and functional connectivity of the brain hubs have been related to behavioral and cognitive impairment in neurological and psychiatric disorders(Crossley et al., 2014; van den Heuvel and Sporns, 2013). These brain regions are intensively connected with other nodes (Buckner et al., 2009; Tomasi et al., 2015; Tomasi and Volkow, 2010, 2011) and the functional hubs are largely overlapped with subregions of the default-mode network(DMN), a network related to selfrelated processes such as self-reference(Sheline et al., 2009), autobiographical memory(Spreng and Grady, 2010) and rumination(Hamilton et al., 2011). Impairments in these hubs have been found in previous studies as they are highly susceptible to disconnection and dysfunction caused by psychiatric disorders due to their high level of centrality. "
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    ABSTRACT: The loss of an only child is a negative life event and may potentially increase the risk of psychiatric disorders. However, the psychological consequences of the loss of an only child and the associated neural mechanisms remain largely unexplored. Degree centrality(DC), derived from resting-state functional magnetic resonance imaging(fMRI), was used to examine network communication in 22 older adults who lost their only child and 23 matched controls. The older adults who lost their only child exhibited an ineffective coping style. They also showed decreased distant and local DC in the precuneus and left inferior parietal lobule and decreased distant DC in the bilateral dorsolateral prefrontal cortex(DLPFC). Furthermore, the decreased local and distant DC of these regions and the decreased DLPFC-precuneus connectivity strength were negatively correlated with negative coping scores in the loss group but not in the controls. Overall, the results suggested a model that the impaired neural network communication of brain hubs within the default mode network(DMN) and central executive network(CEN) were associated with a negative coping style in older adults who lost their only child. The decreased connectivity of the hubs can be identified as a neural risk factor that is related to future psychopathology.
    Full-text · Article · Sep 2015 · Biological psychology
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