Article

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: 9.81). 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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    • "The parahippocampal region is associated with contextual associations or episodic memory and shows a familiarity effect during repetition of tasks, with greater activation during novel as compared with familiar tasks (O'Kane et al. 2005). Depressed individuals have shown greater activation in the left parahippocampal gyrus relative to controls, during encoding of an associative learning paradigm (Werner et al. 2009) and in processing negative pictures (Sheline et al. 2009). Reductions in parahippocampal activation have similarly been observed in MDD patient following treatment with antidepressant medication (Kennedy et al. 2001; Delaveau et al. 2011). "
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    ABSTRACT: Background Dysfunctional attitudes are a feature of depression that has been correlated with receptor binding abnormalities in limbic and cortical regions. We sought to investigate the functional neuroanatomy of dysfunctional attitudes in major depressive disorder (MDD) and the effects of treatment with cognitive-behavioural therapy (CBT).Method Participants were 16 patients with unipolar depression in an acute depressive episode (mean age 40.0 years) and 16 matched healthy controls (mean age 39.9 years). Patients were medication free and received a course of treatment with CBT. All participants underwent functional magnetic resonance imaging (fMRI) scans at baseline and at week 16, prior to the initiation of therapy and following the course of CBT for patients. During each fMRI scan, participants indicated their attributions to statements from a modified Dysfunctional Attitudes Scale (mDAS-48).Results MDD patients in an acute depressive episode endorsed a greater number of extreme responses to DAS statements, which normalized following CBT treatment. Extreme attributions were associated with greater activation in the left hippocampal region, inferior parietal lobe and precuneus in MDD patients as compared with healthy controls as a main effect of group. An interaction effect was found in the left parahippocampal region, which showed less attenuation in MDD patients at the follow-up scan relative to healthy controls.Conclusions Attenuation of activity in the parahippocampal region may be indicative of an improvement in dysfunctional thinking following CBT treatment in depression, while persistent engagement of regions involved in attentional processing and memory retrieval with extreme attributions reflects a trait feature of depression.
    Psychological Medicine 10/2014; 45(07):1-9. DOI:10.1017/S0033291714002529 · 5.43 Impact Factor
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    • "The DMN has recently been shown to be important in self-referential activities [Fox et al., 2005; Fransson 2005]. According to previous studies, there are striking differences between the DMNs of patients with major depressive disorder and healthy control participants [Johnson et al., 2009; Sheline et al., 2009; Zhu et al., 2012]. "
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    ABSTRACT: Resting-state studies conducted with stroke patients are scarce. The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of brain rewiring after stroke and plasticity changes. This study sought to identify dynamic changes in the functional organization of the default mode network (DMN) of stroke patients at three months after stroke. Eleven patients (eight male and three female; age range: 48–72) with right cortical and subcortical ischemic infarctions and 17 controls (eleven males and six females; age range: 57–69) were assessed by neurological and neuropsychological examinations and scanned with resting-state functional magnetic ressonance imaging. First, we explored group differences in functional activity within the DMN by means of probabilistic independent component analysis followed by a dual regression approach. Second, we estimated functional connectivity between 11 DMN nodes both locally by means of seed-based connectivity analysis, as well as globally by means of graph-computation analysis. We found that patients had greater DMN activity in the left precuneus and the left anterior cingulate gyrus when compared with healthy controls (P < 0.05 family-wise error corrected). Seed-based connectivity analysis showed that stroke patients had significant impairment (P = 0.014; threshold = 2.00) in the connectivity between the following five DMN nodes: left superior frontal gyrus (lSFG) and posterior cingulate cortex (t = 2.01); left parahippocampal gyrus and right superior frontal gyrus (t = 2.11); left parahippocampal gyrus and lSFG (t = 2.39); right parietal and lSFG (t = 2.29). Finally, mean path length obtained from graph-computation analysis showed positive correlations with semantic fluency test (r s = 0.454; P = 0.023), phonetic fluency test (r s = 0.523; P = 0.007) and the mini mental state examination (r s = 0.528; P = 0.007). In conclusion, the ability to regulate activity of the DMN appears to be a central part of normal brain function in stroke patients. Our study expands the understanding of the changes occurring in the brain after stroke providing a new avenue for investigating lesion-induced network plasticity. Hum Brain Mapp, 2014. © 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
    Human Brain Mapping 10/2014; 36(2). DOI:10.1002/hbm.22648 · 6.92 Impact Factor
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    • "For instance, the DMN– FPCN (fronto-parietal control network) relationship is predictive of intelligence (Cole et al., 2012). Moreover, lack of DMN suppression is observed in several mental illness such as schizophrenia (Whitfield-Gabrieli et al., 2009; Anticevic et al., 2011; Metzak et al., 2011; Nejad et al., 2011; Dreher et al., 2012; Fatjó-Vilas et al., 2012) and depression (Sheline et al., 2009; Hamilton et al., 2011). "
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    Neuropsychologia 10/2014; 63. DOI:10.1016/j.neuropsychologia.2014.07.035 · 3.45 Impact Factor
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