Depressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical Neuroscience

Abstract

The intuitive association between self-focused rumination in major depressive disorder (MDD) and the self-referential operations performed by the brain's default-mode network (DMN) has prompted interest in examining the role of the DMN in MDD. In this article, we present meta-analytic findings showing reliably increased functional connectivity between the DMN and subgenual prefrontal cortex (sgPFC)-connectivity that often predicts levels of depressive rumination. We also present meta-analytic findings that, while there is reliably increased regional cerebral blood flow in sgPFC in MDD, no such abnormality has been reliably observed in nodes of the DMN. We then detail a model that integrates the body of research presented. In this model, we propose that increased functional connectivity between sgPFC and the DMN in MDD represents an integration of the self-referential processes supported by the DMN with the affectively laden, behavioral withdrawal processes associated with sgPFC-an integration that produces a functional neural ensemble well suited for depressive rumination and that, in MDD, abnormally taxes only sgPFC and not the DMN. This synthesis explains a broad array of existing data concerning the neural substrates of depressive rumination and provides an explicit account of functional abnormalities in sgPFC in MDD.

Keywords: Default-mode network; Intrinsic functional connectivity; Major depressive disorder; Medial-dorsal thalamus; Rumination; Subgenual prefrontal cortex.

Figure 1

Regions showing reliably increased connectivity with the default-mode network in major depressive disorder.

Figure 2

Maps of the default-mode network (DMN; red) and (in blue) meta-analytically reliable regional cerebral blood flow differences between samples with major depressive disorder (MDD) and healthy control (CTL) samples.

Figure 3

Graphical rendering of our DMN-sgPFC functional integration model of depressive rumination. Orange nodes and connections represent normal functionality; red nodes and connections represent depressotypic functioning. Note: We present our model using left- and right-cerebral hemisphere underlays not to indicate inter-hemispheric anomalies associated with MDD, but to juxtapose DMN functioning in depressed and non-depressed individuals.