Default-Mode and TaskPositive Network Activity in Major Depressive Disorder: Implications for Adaptive and Maladaptive Rumination

Department of Psychology, Stanford University, Stanford, California 94305, USA.
Biological psychiatry (Impact Factor: 10.26). 04/2011; 70(4):327-33. DOI: 10.1016/j.biopsych.2011.02.003
Source: PubMed


Major depressive disorder (MDD) has been associated reliably with ruminative responding; this kind of responding is composed of both maladaptive and adaptive components. Levels of activity in the default-mode network (DMN) relative to the task-positive network (TPN), as well as activity in structures that influence DMN and TPN functioning, may represent important neural substrates of maladaptive and adaptive rumination in MDD.
We used a unique metric to estimate DMN dominance over TPN from blood oxygenation level-dependent data collected during eyes-closed rest in 17 currently depressed and 17 never-disordered adults. We calculated correlations between this metric of DMN dominance over TPN and the depressive, brooding, and reflective subscales of the Ruminative Responses Scale, correcting for associations between these measures both with one another and with severity of depression. Finally, we estimated and compared across groups right fronto-insular cortex (RFIC) response during initiations of ascent in DMN and in TPN activity.
In the MDD participants, increasing levels of DMN dominance were associated with higher levels of maladaptive, depressive rumination and lower levels of adaptive, reflective rumination. Moreover, our RFIC state-change analysis showed increased RFIC activation in the MDD participants at the onset of increases in TPN activity; conversely, healthy control participants exhibited increased RFIC response at the onset of increases in DMN activity.
These findings support a formulation in which the DMN undergirds representation of negative, self-referential information in depression, and the RFIC, when prompted by increased levels of DMN activity, initiates an adaptive engagement of the TPN.

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    • "Summarizing, this study demonstrates that DMN alterations persist even after full recovery of MDEs. Observed neural activation patterns were related to rumination, which is a well-established indicator of MDD severity (Hamilton et al., 2011). Brain systems level analyses mirrored the aberrant DMN suppression in rMDD patients and underlined the specific role of the amPFC as mediator of these effects (Lemogne et al., 2012; Chen et al., 2013; Li et al., 2013). "
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    ABSTRACT: Insufficient default mode network (DMN) suppression was linked to increased rumination in symptomatic Major Depressive Disorder (MDD). Since rumination is known to predict relapse and a more severe course of MDD, we hypothesized that similar DMN alterations might also exist during full remission of MDD (rMDD), a condition known to be associated with increased relapse rates specifically in patients with adolescent onset. Within a cross-sectional functional magnetic resonance imaging study activation and functional connectivity (FC) were investigated in 120 adults comprising 78 drug-free rMDD patients with adolescent- (n = 42) and adult-onset (n = 36) as well as 42 healthy controls (HC), while performing the n-back task. Compared to HC, rMDD patients showed diminished DMN deactivation with strongest differences in the anterior-medial prefrontal cortex (amPFC), which was further linked to increased rumination response style. On a brain systems level, rMDD patients showed an increased FC between the amPFC and the dorsolateral prefrontal cortex, which constitutes a key region of the antagonistic working-memory network. Both whole-brain analyses revealed significant differences between adolescent-onset rMDD patients and HC, while adult-onset rMDD patients showed no significant effects. Results of this study demonstrate that reduced DMN suppression exists even after full recovery of depressive symptoms, which appears to be specifically pronounced in adolescent-onset MDD patients. Our results encourage the investigation of DMN suppression as a putative predictor of relapse in clinical trials, which might eventually lead to important implications for antidepressant maintenance treatment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    Full-text · Article · Mar 2015 · Journal of Psychiatric Research
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    • "Reduced FC between the subgenual and perigenual ACC can therefore be a vulnerability factor that makes individuals more susceptible to depression or makes it more difcult to exit a depressive state (Holtzheimer and Mayberg, 2011). The nding of reduced FC between the BA10p seed and the right anterior insular cortex in the depressed group replicated studies that reported reduced FC between the insula and regions of the DMN (Veer et al., 2010; Hamilton et al., 2011). During rest, BA10p is activated as part of the DMN, which undertakes internalstate processing such as self-referential thinking. "
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    ABSTRACT: Major depressive disorder has been associated with abnormal resting-state functional connectivity (FC), especially in cognitive processing and emotional regulation networks. Although studies have found abnormal FC in regions of the default mode network (DMN), no study has investigated the FC of specific regions within the anterior DMN based on cytoarchitectonic subdivisions of the antero-medial pre-frontal cortex (PFC). Studies from different areas in the field have shown regions within the anterior DMN to be involved in emotional intelligence. Although abnormalities in this region have been observed in depression, the relationship between the ventromedial PFC (vmPFC) function and emotional intelligence has yet to be investigated in depressed individuals. Twenty-one medication-free, non-treatment resistant, depressed patients and 21 healthy controls underwent a resting state functional magnetic resonance imaging session. The participants also completed an ability-based measure of emotional intelligence: the Mayer-Salovey-Caruso Emotional Intelligence Test. FC maps of Brodmann areas (BA) 25, 10m, 10r, and 10p were created and compared between the two groups. Mixed-effects analyses showed that the more anterior seeds encompassed larger areas of the DMN. Compared to healthy controls, depressed patients had significantly lower connectivity between BA10p and the right insula and between BA25 and the perigenual anterior cingulate cortex. Exploratory analyses showed an association between vmPFC connectivity and emotional intelligence. These results suggest that individuals with depression have reduced FC between antero-medial PFC regions and regions involved in emotional regulation compared to control subjects. Moreover, vmPFC functional connectivity appears linked to emotional intelligence. © The Author 2015. Published by Oxford University Press on behalf of CINP.
    Full-text · Article · Mar 2015 · The International Journal of Neuropsychopharmacology
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    • "Systems-level perspectives highlight three largescale brain networks and their roles in these psychological processes: the salience network (SN; Seeley et al. 2007), the default-mode network (DMN; Raichle et al. 2001) and the executive control network (ECN; Fox et al. 2005). The insulae and ACC are critical nodes of the SN, which plays a role in directing attention toward either internal or external stimuli by toggling dynamic activity between the typically anticorrelated DMN and ECN (Fox et al. 2005; Sridharan, Levitin & Menon 2008; Hamilton et al. 2011). As the DMN is generally associated with endogenous information processing and the ECN with exogenous information processing, intermittent failures to adequately suppress the DMN (Sonuga-Barke & Castellanos 2007) and/or maladaptive interactions between components of these two networks (Weissman et al. 2006; Kelly et al. 2008) represent systems-level mechanisms contributing to suboptimal goal-directed behavior in various neuropsychiatric conditions (Menon 2011) and during nicotine withdrawal (Sutherland et al. 2012b). "
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    ABSTRACT: Attenuated activity in performance-monitoring brain regions following erroneous actions may contribute to the repetition of maladaptive behaviors such as continued drug use. Externalizing is a broad personality construct characterized by deficient impulse control, vulnerability to addiction and reduced neurobiological indices of error processing. The insula and dorsal anterior cingulate cortex (dACC) are regions critically linked with error processing as well as the perpetuation of cigarette smoking. As such, we examined the interrelations between externalizing tendencies, erroneous task performance, and error-related insula and dACC activity in overnight-deprived smokers (n=24) and non-smokers (n=20). Participants completed a self-report measure assessing externalizing tendencies (Externalizing Spectrum Inventory) and a speeded Flanker task during functional magnetic resonance imaging scanning. We observed that higher externalizing tendencies correlated with the occurrence of more performance errors among smokers but not non-smokers. Suggesting a neurobiological contribution to such suboptimal performance among smokers, higher externalizing also predicted less recruitment of the right insula and dACC following error commission. Critically, this error-related activity fully mediated the relationship between externalizing traits and error rates. That is, higher externalizing scores predicted less error-related right insula and dACC activity and, in turn, less error-related activity predicted more errors. Relating such regional activity with a clinically relevant construct, less error-related right insula and dACC responses correlated with higher tobacco craving during abstinence. Given that inadequate error-related neuronal responses may contribute to continued drug use despite negative consequences, these results suggest that externalizing tendencies and/or compromised error processing among subsets of smokers may be relevant factors for smoking cessation success.
    Full-text · Article · Mar 2015 · Addiction Biology
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