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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    • "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.
    Biological psychology 09/2015; 112. DOI:10.1016/j.biopsycho.2015.09.005 · 3.40 Impact Factor
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    • "Regardless of the underlying mechanisms, the observed task-positive connectivity changes of the DMN across a range of tasks and their association with behavior reinforce the perspective (Spreng, 2012; Hampson, Driesen, Skudlarski, Gore, & Constable, 2006) that this network may contribute a wide range of functional deficits spanning diverse domains. For instance, the view that the DMN is suppressed during most tasks could hardly reconcile the innumerable findings linking this network to diverse task-related functional abnormalities spanning both internal and external domains, including motor control deficits (e.g., Parkinson disease; Tessitore et al., 2012; Van Dijk et al., 2010), attention deficits (e.g., ADHD; Liddle et al., 2011; Uddin et al., 2008), social skill deficits (e.g., autism; Lynch et al., 2013; Washington et al., 2013; Murdaugh et al., 2012; Spencer et al., 2012), dysregulated mood (e.g., bipolar disorder, depression; Sambataro, Wolf, Pennuto, Vasic, & Wolf, 2013; Marchetti, Koster, Sonuga-Barke, & De Raedt, 2012; Ongur et al., 2010; Sheline et al., 2009), psychosis (e.g., schizophrenia; Guo et al., 2014; Jang et al., 2011; Ongur et al., 2010; Pomarol-Clotet et al., 2008), and memory loss/cognitive disabilities (e.g., Alzheimer's disease and dementia; Qi et al., 2010; Greicius, Srivastava, Reiss, & Menon, 2004). "
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    ABSTRACT: The default mode network (DMN) was first recognized as a set of brain regions demonstrating consistently greater activity during rest than during a multitude of tasks. Originally, this network was believed to interfere with goal-directed behavior based on its decreased activity during many such tasks. More recently, however, the role of the DMN during goal-directed behavior was established for internally oriented tasks, in which the DMN demonstrated increased activity. However, the well-documented hub position and information-bridging potential of midline DMN regions indicate there is more to uncover regarding its functional contributions to goal-directed tasks, which may be based on its functional interactions rather than its level of activation. An investigation of task-related changes in DMN functional connectivity during a series of both internal and external tasks would provide the requisite investigation for examining the role of the DMN during goal-directed task performance. In this study, 20 participants underwent fMRI while performing six tasks spanning diverse internal and external domains in addition to a resting-state scan. We hypothesized that the DMN would demonstrate "task-positive" (i.e., positively contributing to task performance) changes in functional connectivity relative to rest regardless of the direction of task-related changes in activity. Indeed, our results demonstrate significant increases in DMN connectivity with task-promoting regions (e.g., anterior insula, inferior frontal gyrus, middle frontal gyrus) across all six tasks. Furthermore, canonical correlation analyses indicated that the observed task-related connectivity changes were significantly associated with individual differences in task performance. Our results indicate that the DMN may not only support a "default" mode but may play a greater role in both internal and external tasks through flexible coupling with task-relevant brain regions.
    Journal of Cognitive Neuroscience 08/2015; 27(12):1-13. DOI:10.1162/jocn_a_00859 · 4.09 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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    Brain Structure and Function 07/2015; DOI:10.1007/s00429-015-1087-7 · 5.62 Impact Factor
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