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

Published:February 24, 2015DOI:https://doi.org/10.1016/j.biopsych.2015.02.020

      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

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      References

        • Morrow J.
        • Nolen-Hoeksema S.
        Effects of responses to depression on the remediation of depressive affect.
        J Pers Soc Psychol. 1990; 58: 519-527
        • Nolenhoeksema S.
        Responses to depression and their effects on the duration of depressive episodes.
        J Abnorm Psychol. 1991; 100: 569-582
        • Whitmer A.J.
        • Gotlib I.H.
        An attentional scope model of rumination.
        Psychol Bull. 2013; 139: 1036-1061
        • Kuehner C.
        • Weber I.
        Responses to depression in unipolar depressed patients: An investigation of Nolen-Hoeksema’s response styles theory.
        Psychol Med. 1999; 29: 1323-1333
        • Nolen-Hoeksema S.
        • Wisco B.E.
        • Lyubomirsky S.
        Rethinking rumination.
        Perspect Psychol Sci. 2008; 3: 400-424
        • Hamilton J.P.
        • Furman D.J.
        • Chang C.
        • Thomason M.E.
        • Dennis E.
        • Gotlib I.H.
        Default-mode and task-positive network activity in major depressive disorder: Implications for adaptive and maladaptive rumination.
        Biol Psychiatry. 2011; 70: 327-733
        • Lyubomirsky S.
        • Tucker K.L.
        • Caldwell N.D.
        • Berg K.
        Why ruminators are poor problem solvers: Clues from the phenomenology of dysphoric rumination.
        J Pers Soc Psychol. 1999; 77: 1041-1060
        • Yeo B.T.T.
        • Krienen F.M.
        • Sepulcre J.
        • Sabuncu M.R.
        • Lashkari D.
        • Hollinshead M.
        • et al.
        The organization of the human cerebral cortex estimated by intrinsic functional connectivity.
        J Neurophysiol. 2011; 106: 1125-1165
        • Anticevic A.
        • Cole M.W.
        • Murray J.D.
        • Corlett P.R.
        • Wang X.J.
        • Krystal J.H.
        The role of default network deactivation in cognition and disease.
        Trends Cogn Sci. 2012; 16: 584-592
        • Whitfield-Gabrieli S.
        • Ford J.M.
        Default mode network activity and connectivity in psychopathology.
        Annu Rev Clin Psychol. 2012; 8: 49-76
        • Menon V.
        Large-scale brain networks and psychopathology: A unifying triple network model.
        Trends Cogn Sci. 2011; 15: 483-506
        • Fox M.D.
        • Snyder A.Z.
        • Vincent J.L.
        • Corbetta M.
        • Van Essen D.C.
        • Raichle M.E.
        The human brain is intrinsically organized into dynamic, anticorrelated functional networks.
        Proc Natl Acad Sci U S A. 2005; 102: 9673-9678
        • Tom S.M.
        • Fox C.R.
        • Trepel C.
        • Poldrack R.A.
        The neural basis of loss aversion in decision-making under risk.
        Science. 2007; 315: 515-518
        • Paulus M.P.
        • Frank L.R.
        Ventromedial prefrontal cortex activation is critical for preference judgments.
        Neuroreport. 2003; 14: 1311-1315
        • Plassmann H.
        • O’Doherty J.
        • Rangel A.
        Orbitofrontal cortex encodes willingness to pay in everyday economic transactions.
        J Neurosci. 2007; 27: 9984-9988
        • Fellows L.K.
        • Farah M.J.
        The role of ventromedial prefrontal cortex in decision making: Judgment under uncertainty or judgment per se?.
        Cereb Cortex. 2007; 17: 2669-2674
        • Plassmann H.
        • O’Doherty J.
        • Shiv B.
        • Rangel A.
        Marketing actions can modulate neural representations of experienced pleasantness.
        Proc Natl Acad Sci U S A. 2008; 105: 1050-1054
        • de Araujo I.E.
        • Rolls E.T.
        • Velazco M.I.
        • Margot C.
        • Cayeux I.
        Cognitive modulation of olfactory processing.
        Neuron. 2005; 46: 671-679
        • Sestieri C.
        • Corbetta M.
        • Romani G.L.
        • Shulman G.L.
        Episodic memory retrieval, parietal cortex, and the default mode network: Functional and topographic analyses.
        J Neurosci. 2011; 31: 4407-4420
        • Spreng R.N.
        • Mar R.A.
        • Kim A.S.N.
        The common neural basis of autobiographical memory, prospection, navigation, theory of mind, and the default mode: A quantitative meta-analysis.
        J Cogn Neurosci. 2009; 21: 489-510
        • Binder J.R.
        • Desai R.H.
        • Graves W.W.
        • Conant L.L.
        Where is the semantic system? A critical review and meta-analysis of 120 functional neuroimaging studies.
        Cereb Cortex. 2009; 19: 2767-2796
        • Hagmann P.
        • Cammoun L.
        • Gigandet X.
        • Meuli R.
        • Honey C.J.
        • Wedeen V.
        • Sporns O.
        Mapping the structural core of human cerebral cortex.
        PLoS Biol. 2008; 6: 1479-1493
        • Seeley W.W.
        • Menon V.
        • Schatzberg A.F.
        • Keller J.
        • Glover G.H.
        • Kenna H.
        • et al.
        Dissociable intrinsic connectivity networks for salience processing and executive control.
        J Neurosci. 2007; 27: 2349-2356
        • Northoff G.
        • Bermpohl F.
        Cortical midline structures and the self.
        Trends Cogn Sci. 2004; 8: 102-107
        • Mason M.F.
        • Norton M.I.
        • Van Horn J.D.
        • Wegner D.M.
        • Grafton S.T.
        • Macrae C.N.
        Wandering minds: The default network and stimulus-independent thought.
        Science. 2007; 315: 393-395
        • Ralchle M.E.
        • Snyder A.Z.
        A default mode of brain function: A brief history of an evolving idea.
        Neuroimage. 2007; 37: 1083-1090
        • Harrison B.J.
        • Pujol J.
        • Lopez-Sola M.
        • Hernandez-Ribas R.
        • Deus J.
        • Ortiz H.
        • et al.
        Consistency and functional specialization in the default mode brain network.
        Proc Natl Acad Sci U S A. 2008; 105: 9781-9786
        • Laird A.R.
        • Eickhoff S.B.
        • Li K.
        • Robin D.A.
        • Glahn D.C.
        • Fox P.T.
        Investigating the functional heterogeneity of the default mode network using coordinate-based meta-analytic modeling.
        J Neurosci. 2009; 29: 14496-14505
        • Uddin L.Q.
        • Kelly A.M.C.
        • Biswal B.B.
        • Castellanos F.X.
        • Milham M.P.
        Functional connectivity of default mode network components: Correlation, anticorrelation, and causality.
        Hum Brain Mapp. 2009; 30: 625-637
        • Alexopoulos G.S.
        • Hoptman M.J.
        • Kanellopoulos D.
        • Murphy C.F.
        • Lim K.O.
        • Gunning F.M.
        Functional connectivity in the cognitive control network and the default mode network in late-life depression.
        J Affect Disord. 2012; 139: 56-65
        • Sambataro F.
        • Wolf N.D.
        • Pennuto M.
        • Vasic N.
        • Wolf R.C.
        Revisiting default mode network function in major depression: Evidence for disrupted subsystem connectivity.
        Psychol Med. 2014; 44: 2041-2051
        • Berman M.G.
        • Peltier S.
        • Nee D.E.
        • Kross E.
        • Deldin P.J.
        • Jonides J.
        Depression, rumination and the default network.
        Soc Cogn Affect Neurosci. 2011; 6: 548-555
        • Gaffrey M.S.
        • Luby J.L.
        • Botteron K.
        • Repovs G.
        • Barch D.M.
        Default mode network connectivity in children with a history of preschool onset depression.
        J Child Psychol Psychiatry. 2012; 53: 964-972
        • Greicius M.D.
        • Flores B.H.
        • Menon V.
        • Glover G.H.
        • Solvason H.B.
        • Kenna H.
        • et al.
        Resting-state functional connectivity in major depression: Abnormally increased contributions from subgenual cingulate cortex and thalamus.
        Biol Psychiatry. 2007; 62: 429-437
        • Zhu X.L.
        • Wang X.
        • Xiao J.
        • Liao J.
        • Zhong M.T.
        • Wang W.
        • et al.
        Evidence of a dissociation pattern in resting-state default mode network connectivity in first-episode, treatment-naive major depression patients.
        Biol Psychiatry. 2012; 71: 611-617
        • Hamilton J.P.
        • Chen G.
        • Thomason M.E.
        • Johnson R.F.
        • Gotlib I.H.
        Investigating neural primacy in major depressive disorder: Multivariate granger causality analysis of resting-state fMRI time-series data.
        Mol Psychiatry. 2011; 16: 763-772
        • Etkin A.
        • Wager T.D.
        Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia.
        Am J Psychiatry. 2007; 164: 1476-1488
        • Wager T.D.
        • Phan K.L.
        • Liberzon I.
        • Taylor S.F.
        Valence, gender, and lateralization of functional brain anatomy in emotion: A meta-analysis of findings from neuroimaging.
        Neuroimage. 2003; 19: 513-531
        • Hamilton J.P.
        • Etkin A.
        • Furman D.J.
        • Lemus M.G.
        • Johnson R.F.
        • Gotlib I.H.
        Functional neuroimaging of major depressive disorder: A meta-analysis and new integration of baseline activation and neural response data.
        Am J Psychiatry. 2012; : 693-703
        • Cox R.W.
        AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages.
        Comput Biomed Res. 1996; 29: 162-173
        • Greicius M.D.
        • Krasnow B.
        • Reiss A.L.
        • Menon V.
        Functional connectivity in the resting brain: A network analysis of the default mode hypothesis.
        Proc Natl Acad Sci U S A. 2003; 100: 253-258
        • Drevets W.C.
        • Price J.L.
        • Simpson J.R.
        • Todd R.D.
        • Reich T.
        • Vannier M.
        • Raichle M.E.
        Subgenual prefrontal cortex abnormalities in mood disorders.
        Nature. 1997; 386: 824-827
        • Mayberg H.S.
        • Liotti M.
        • Brannan S.K.
        • McGinnis S.
        • Mahurin R.K.
        • Jerabek P.A.
        • et al.
        Reciprocal limbic-cortical function and negative mood: Converging PET findings in depression and normal sadness.
        Am J Psychiatry. 1999; 156: 675-682
        • Mayberg H.S.
        • Lozano A.M.
        • Voon V.
        • McNeely H.E.
        • Seminowicz D.
        • Hamani C.
        • et al.
        Deep brain stimulation for treatment-resistant depression.
        Neuron. 2005; 45: 651-660
        • Hamani C.
        • Mayberg H.
        • Snyder B.
        • Giacobbe P.
        • Kennedy S.
        • Lozano A.M.
        Deep brain stimulation of the subcallosal cingulate gyrus for depression: Anatomical location of active contacts in clinical responders and a suggested guideline for targeting clinical article.
        J Neurosurg. 2009; 111: 1209-1215
        • Laxton A.W.
        • Neimat J.S.
        • Davis K.D.
        • Womelsdorf T.
        • Hutchison W.D.
        • Dostrovsky J.O.
        • et al.
        Neuronal coding of implicit emotion categories in the subcallosal cortex in patients with depression.
        Biol Psychiatry. 2013; 74: 714-719
        • Murray E.A.
        • Wise S.P.
        • Drevets W.C.
        Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala.
        Biol Psychiatry. 2011; 69: E43-E54
        • Price J.L.
        • Drevets W.C.
        Neural circuits underlying the pathophysiology of mood disorders.
        Trends Cogn Sci. 2012; 16: 61-71
        • Bush G.
        • Luu P.
        • Posner M.I.
        Cognitive and emotional influences in anterior cingulate cortex.
        Trends Cogn Sci. 2000; 4: 215-222
        • Etkin A.
        • Egner T.
        • Kalisch R.
        Emotional processing in anterior cingulate and medial prefrontal cortex.
        Trends Cogn Sci. 2011; 15: 85-93
        • Treynor W.
        • Gonzalez R.
        • Nolen-Hoeksema S.
        Rumination reconsidered: A psychometric analysis.
        Cognit Ther Res. 2003; 27: 247-259
        • Joormann J.
        • Dkane M.
        • Gotlib I.H.
        Adaptive and maladaptive components of rumination? Diagnostic specificity and relation to depressive biases.
        Behav Ther. 2006; 37: 269-280
        • Harrison N.A.
        • Brydon L.
        • Walker C.
        • Gray M.A.
        • Steptoe A.
        • Critchley H.D.
        Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity.
        Biol Psychiatry. 2009; 66: 407-414
        • Critchley H.D.
        • Mathias C.J.
        • Josephs O.
        • O’Doherty J.
        • Zanini S.
        • Dewar B.K.
        • et al.
        Human cingulate cortex and autonomic control: Converging neuroimaging and clinical evidence.
        Brain. 2003; 126: 2139-2152
        • Matthews S.C.
        • Simmons A.N.
        • Arce E.
        • Paulus M.P.
        Dissociation of inhibition from error processing using a parametric inhibitory task during functional magnetic resonance imaging.
        Neuroreport. 2005; 16: 755-760
        • Yang T.T.
        • Simmons A.N.
        • Matthews S.C.
        • Tapert S.F.
        • Frank G.K.
        • Bischoff-Grethe A.
        • et al.
        Adolescent subgenual anterior cingulate activity is related to harm avoidance.
        Neuroreport. 2009; 20: 19-23
        • Zahn R.
        • Moll J.
        • Paiva M.
        • Garrido G.
        • Krueger F.
        • Huey E.D.
        • Grafman J.
        The neural basis of human social values: Evidence from functional MRI.
        Cereb Cortex. 2009; 19: 276-283
        • Masten C.L.
        • Esenberger N.I.
        • Borofsky L.A.
        • McNealy K.
        • Pfeifer J.H.
        • Dapretto M.
        Subgenual anterior cingulate responses to peer rejection: A marker of adolescents’ risk for depression.
        Dev Psychopathol. 2011; 23: 283-292
        • Johansen-Berg H.
        • Gutman D.A.
        • Behrens T.E.J.
        • Matthews P.M.
        • Rushworth M.F.S.
        • Katz E.
        • et al.
        Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression.
        Cereb Cortex. 2008; 18: 1374-1383
        • Freedman L.J.
        • Insel T.R.
        • Smith Y.
        Subcortical projections of area 25 (subgenual cortex) of the macaque monkey.
        J Comp Neurol. 2000; 421: 172-188
        • Alexander G.E.
        • Delong M.R.
        • Strick P.L.
        Parallel organization of functionally segregated circuits linking basal ganglia and cortex.
        Annu Rev Neurosci. 1986; 9: 357-381
        • Sheline Y.I.
        • Price J.L.
        • Yan Z.Z.
        • Mintun M.A.
        Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus.
        Proc Natl Acad Sci U S A. 2010; 107: 11020-11025
        • Luscher B.
        • Shen Q.
        • Sahir N.
        The GABAergic deficit hypothesis of major depressive disorder.
        Mol Psychiatry. 2011; 16: 383-406
        • Northoff G.
        • Walter M.
        • Schulte R.F.
        • Beck J.
        • Dydak U.
        • Henning A.
        • et al.
        GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI.
        Nat Neurosci. 2007; 10: 1515-1517
        • Spreng R.N.
        • Stevens W.D.
        • Chamberlain J.P.
        • Gilmore A.W.
        • Schacter D.L.
        Default network activity, coupled with the frontoparietal control network, supports goal-directed cognition.
        Neuroimage. 2010; 53: 303-317
        • van Leeuwen T.M.
        • den Ouden H.E.M.
        • Hagoort P.
        Effective connectivity determines the nature of subjective experience in grapheme-color synesthesia.
        J Neurosci. 2011; 31: 9879-9884
        • Rubinov M.
        • Sporns O.
        Complex network measures of brain connectivity: Uses and interpretations.
        Neuroimage. 2010; 52: 1059-1069
        • Chen A.C.
        • Oathes D.J.
        • Chang C.
        • Bradley T.
        • Zhou Z.-W.
        • Williams L.M.
        • et al.
        Causal interactions between fronto-parietal central executive and default-mode networks in humans.
        Proc Natl Acad Sci U S A. 2013; 110: 19944-19949
        • Watkins E.
        • Scott J.
        • Wingrove J.
        • Rimes K.
        • Bathurst N.
        • Steiner H.
        • et al.
        Rumination-focused cognitive behaviour therapy for residual depression: A case series.
        Behav Res Ther. 2007; 45: 2144-2154