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

Abstract

Background 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. Methods We used a unique metric to estimate DMN dominance over TPN from blood-oxygen-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. Results 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. Conclusions 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.

Sleep deprivation increases dorsal nexus connectivity to the dorsolateral prefrontal cortex in humans

“…To investigate whether an alteration in DN connectivity could provide a biomarker of therapy response and to determine brain mechanisms of action underlying sleep deprivations antidepressant effects, we examined its influence on resting state default mode network and DN connectivity in healthy humans. Our findings show that sleep deprivation reduced functional connectivity between posterior cingulate cortex and bilateral anterior cingulate cortex (Brodmann area 32), and enhanced connectivity between DN and distinct areas in right dorsolateral prefrontal cortex (Brodmann area 10). These findings are consistent with resolution of dysfunctional brain network connectivity changes observed in depression and suggest changes in prefrontal connectivity with the DN as a brain mechanism of antidepressant therapy action.…”

“…Here, we found that sleep deprivation reduced connectivity on the ACC-PCC axis. This is of particular interest because resting-state DMN dominance is associated with increased maladaptive, depressive rumination, and reduced adaptive, reflective rumination (32). Depressed patients typically fail to down-regulate DMN activity during emotional stimulation (33,34).…”

Increased Default Mode Network Connectivity in Individuals at High Familial Risk for Depression

“…This inverse relationship between the DMN and CEN is reflected in negative connectivity (or anticorrelations) between these two networks in healthy individuals (Fox et al, 2005;Biswal et al, 2010;Whitfield-Gabrieli and Ford, 2012). DMN-CEN anticorrelations may be altered in MDD (Sheline et al, 2010;Hamilton et al, 2011) and may reflect impairments in attentional control or impulsivity ; however, similar to DMN connectivity, DMN-CEN anticorrelations have scarcely been examined in individuals at risk for, but not yet affected by, depression.…”

Is Depressive Rumination Rational?

“…73-118). 16 In effect what Hamilton et al (2011) discovered is that in depressed patients-but not in healthy subjects-greater DMN activity relative to TPN activity correlated with depressive rumination, but not with pondering. This discovery is important because it dovetails neatly with two converging lines of research that might be able to contribute to a theoretically motivated explanation of depression of the sort envisioned by Hempel 50 years ago.…”

“…The relevance of this distinction between the different types of ruminative cognition to MDD's neural substrate has recently been established by Hamilton et al (2011). The authors discovered that dominance by the brain's "default mode network" (DMN) positively correlates with elevated levels of brooding, but with only low levels of pondering (cf., Hamilton, Chen, & Gotlib, 2013).…”