The role of default network deactivation in cognition and disease

Anticevic, Alan; Cole, Michael W.; Murray, John D.; Corlett, Philip R.; Wang, Xiao-Jing; Krystal, John H.

doi:10.1016/j.tics.2012.10.008

Cited by 978Functional Brain Connectivity StudiesMind wandering and attentionCognitive Functions and Memory

The role of default network deactivation in cognition and disease

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Anticevic, Alan, Cole, Michael W., Murray, John D., Corlett, Philip R., Wang, Xiao-Jing, Krystal, John H.·2012·Trends in Cognitive Sciences

DOI 10.1016/j.tics.2012.10.008PMC PMC3501603

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Abstract

A considerable body of evidence has accumulated over recent years on the functions of the default-mode network (DMN)--a set of brain regions whose activity is high when the mind is not engaged in specific behavioral tasks and low during focused attention on the external environment. In this review, we focus on DMN suppression and its functional role in health and disease, summarizing evidence that spans several disciplines, including cognitive neuroscience, pharmacological neuroimaging, clinical neuroscience, and theoretical neuroscience. Collectively, this research highlights the functional relevance of DMN suppression for goal-directed cognition, possibly by reducing goal-irrelevant functions supported by the DMN (e.g., mind-wandering), and illustrates the functional significance of DMN suppression deficits in severe mental illness.

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Disruption of DMN function occurs in psychiatric illnesses.
“disruption of DMN function in psychiatric illnesses”
From SSRI Treatment Response Prediction in Depression Based on Brain Activation by Emotional Stimuli (2020) · cites this paper as [20]
Negatively biased self-generated thoughts and heightened activity of the DMN have been associated with depression.
“For example, negatively biased self-generated thoughts and heightened activity of the DMN have been associated with depression (20, 21, 54, 56–58), as well as maladaptive rumination (55).”
From SSRI Treatment Response Prediction in Depression Based on Brain Activation by Emotional Stimuli (2020) · cites this paper as [20]
During working memory tasks, the control network typically shows increased activation while the default network deactivates, presumably reflecting suppression of task-unrelated thoughts.
“During working memory tasks, for example, the control network typically shows increased activation while the default network deactivates, presumably reflecting the suppression of task-unrelated thoughts during cognitive control [16].”
From Creative Cognition and Brain Network Dynamics (2016) · cites this paper as [16]
The magnitude of default network-dorsal attention network anticorrelation relates to cognitive performance and certain psychopathological disorders.
“The magnitude of anticorrelation also relates to cognitive performance145 and certain psychopathological disorders (see below).146–148”
From The default network and self-generated thought: component processes, dynamic control, and clinical relevance (2014) · cites this paper as [148]
Mood disorders including major depressive disorder and bipolar disorder are associated with enhanced activity and connectivity of default network structures with key regions of the limbic and/or salience networks.
“For example, mood disorders including major depressive disorder and bipolar disorder are associated with enhanced activity and connectivity of DN structures with key regions of the limbic and/or salience networks.147,148,215–219”
From The default network and self-generated thought: component processes, dynamic control, and clinical relevance (2014) · cites this paper as [148]

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Dopamine Supports Coupling of Attention-Related Networks
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S ection of P sychology : MINDWANDERING AND COGNITIVE STRUCTURE*, †
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Limbic over-activity in depression during preserved performance on the n-back task
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Working Memory Encoding and Maintenance Deficits in Schizophrenia: Neural Evidence for Activation and Deactivation Abnormalities
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Modulation of steady state functional connectivity in the default mode and working memory networks by cognitive load
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Correlated structural and functional brain abnormalities in the default mode network in schizophrenia patients
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Theta power during encoding predicts subsequent‐memory performance and default mode network deactivation
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Cerebral blood flow in posterior cortical nodes of the default mode network decreases with task engagement but remains higher than in most brain regions
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Task-induced deactivation and the "resting" state
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Decreased Efficiency of Task-Positive and Task-Negative Networks During Working Memory in Schizophrenia
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Attractor networks
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Modafinil modulation of the default mode network
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Modulation of the default mode network is task-dependant in chronic schizophrenia patients.
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Patients with Schizophrenia Fail to Up-Regulate Task-Positive and Down-Regulate Task-Negative Brain Networks: An fMRI Study Using an ICA Analysis Approach
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Common and Differential Pathophysiological Features Accompany Comparable Cognitive Impairments in Medication-Free Patients with Schizophrenia and in Healthy Aging Subjects
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Effect of the Interleukin-1β Gene on Dorsolateral Prefrontal Cortex Function in Schizophrenia: A Genetic Neuroimaging Study
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Impaired temporoparietal deactivation with working memory load in antipsychotic-naïve patients with first-episode schizophrenia
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Brain functional abnormality in schizo-affective disorder: an fMRI study
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Spontaneous Activity in a Large Neural Net: Between Chaos and Noise
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[45]Andrews-Hanna JR 2012 The Brain’s Default Network and Its Adaptive Role in Internal Mentation Neuroscientist 18 251 270 21677128 PMC3553600

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The default network and self-generated thought: component processes, dynamic control, and clinical relevance
Andrews‐Hanna, J. R., Smallwood, J., & Spreng, R. N. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12360 · Cited by 2,102 · see citing works
Intrinsic and task-evoked network architectures of the human brain
Cole, M. W., Bassett, D. S., Power, J. D., Braver, T. S., & Petersen, S. E. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.014 · Cited by 1,564 · see citing works
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Mind-wandering as spontaneous thought: a dynamic framework
Christoff, K., Irving, Z. C., Fox, K. C. R., Spreng, R. N., & Andrews-Hanna, J. R. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.113 · Cited by 1,376 · see citing works
Creative Cognition and Brain Network Dynamics
Beaty, R. E., Benedek, M., Silvia, P. J., & Schacter, D. L. (2016) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2015.10.004 · Cited by 1,105 · see citing works
“During working memory tasks, for example, the control network typically shows increased activation while the default network deactivates, presumably reflecting the suppression of task-unrelated thoughts during cognitive control [16].”
Background
Network abnormalities and interneuron dysfunction in Alzheimer disease
Palop, J. J., & Mucke, L. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.141 · Cited by 1,022 · see citing works
Depressive rumination, the default-mode network, and the dark matter of clinical neuroscience
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Default mode network mechanisms of transcranial magnetic stimulation in depression
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The wandering brain: meta-analysis of functional neuroimaging studies of mind-wandering and related spontaneous thought processes
Fox, K. C. R., Spreng, R. N., Ellamil, M., Andrews-Hanna, J. R., & Christoff, K. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.02.039 · Cited by 690 · see citing works
Lower synaptic density is associated with depression severity and network alterations
Holmes, S. E., Scheinost, D., Finnema, S. J., Naganawa, M., Davis, M. T., DellaGioia, N., Nabulsi, N., Matuskey, D., Angarita, G. A., Pietrzak, R. H., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09562-7 · Cited by 484 · see citing works
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The Frontoparietal Control System: A Central Role in Mental Health
Cole, M. W., Repovš, G., & Anticevic, A. (2014) · The Neuroscientist · doi:10.1177/1073858414525995 · Cited by 461 · see citing works
Dynamic cooperation and competition between brain systems during cognitive control
Cocchi, L., Zalesky, A., Fornito, A., & Mattingley, J. B. (2013) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2013.08.006 · Cited by 429 · see citing works
To create or to recall? Neural mechanisms underlying the generation of creative new ideas
Benedek, M., Jauk, E., Fink, A., Koschutnig, K., Reishofer, G., Ebner, F., & Neubauer, A. C. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2013.11.021 · Cited by 407 · see citing works
Episodic memory in normal aging and Alzheimer disease: Insights from imaging and behavioral studies
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Common Dysfunction of Large-Scale Neurocognitive Networks Across Psychiatric Disorders
Sha, Z., Wager, T. D., Mechelli, A., & He, Y. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.11.011 · Cited by 367 · see citing works
Somatostatin-Positive Gamma-Aminobutyric Acid Interneuron Deficits in Depression: Cortical Microcircuit and Therapeutic Perspectives
Fee, C., Banasr, M., & Sibille, E. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.05.024 · Cited by 329 · see citing works
Meditation leads to reduced default mode network activity beyond an active task
Garrison, K. A., Zeffiro, T. A., Scheinost, D., Constable, R. T., & Brewer, J. A. (2015) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/s13415-015-0358-3 · Cited by 295 · see citing works
“Previous work suggests that increased DMN activity may interfere with cognitive performance, and decreased DMN activity is associated with improved performance (for review, see Anticevic et al., 2012).”
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Ketamine Treatment and Global Brain Connectivity in Major Depression
Abdallah, C. G., Averill, L. A., Collins, K. A., Geha, P., Schwartz, J., Averill, C., DeWilde, K. E., Wong, E., Anticevic, A., Tang, C. Y., et al. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.186 · Cited by 300 · see citing works
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Alterations in resting-state functional connectivity link mindfulness meditation with reduced interleukin-6: a randomized controlled trial
Creswell, J. D., Taren, A. A., Lindsay, E. K., Greco, C. M., Gianaros, P. J., Fairgrieve, A., Marsland, A. L., Brown, K. W., Way, B. M., Rosen, R. K., et al. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.01.008 · Cited by 299 · see citing works
“There has been considerable recent interest in characterizing resting-state neural networks, such as the DMN, and understanding their role in health and disease (23).”
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Brain correlates of hypnosis: A systematic review and meta-analytic exploration
Landry, M., Lifshitz, M., & Raz, A. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.02.020 · Cited by 295 · see citing works
High intelligence: A risk factor for psychological and physiological overexcitabilities
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N-Methyl-D-Aspartate Receptor Antagonist Effects on Prefrontal Cortical Connectivity Better Model Early Than Chronic Schizophrenia
Anticevic, A., Corlett, P. R., Cole, M. W., Savic, A., Gancsos, M., Tang, Y., Repovs, G., Murray, J. D., Driesen, N. R., Morgan, P. T., et al. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.07.022 · Cited by 181 · see citing works
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Goal-congruent default network activity facilitates cognitive control
Spreng, R. N., DuPre, E., Selarka, D., Garcia, J., Gojkovic, S., Mildner, J., Luh, W.-M., & Turner, G. R. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.2815-14.2014 · Cited by 167 · see citing works
Early-course unmedicated schizophrenia patients exhibit elevated prefrontal connectivity associated with longitudinal change
Anticevic, A., Hu, X., Xiao, Y., Hu, J., Li, F., Bi, F., Cole, M. W., Savic, A., Yang, G. J., Repovs, G., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2310-14.2015 · Cited by 178 · see citing works
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Intranasal Insulin Enhanced Resting-State Functional Connectivity of Hippocampal Regions in Type 2 Diabetes
Zhang, H., Hao, Y., Manor, B., Novak, P., Milberg, W., Zhang, J., Fang, J., & Novak, V. (2015) · Diabetes · doi:10.2337/db14-1000 · Cited by 176 · see citing works
State-dependent variability of dynamic functional connectivity between frontoparietal and default networks relates to cognitive flexibility
Douw, L., Wakeman, D. G., Tanaka, N., Liu, H., & Stufflebeam, S. M. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.09.034 · Cited by 162 · see citing works
Association between abnormal default mode network activity and suicidality in depressed adolescents
Zhang, S., Chen, J.-M., Kuang, L., Cao, J., Zhang, H., Ai, M., Wang, W., Zhang, S.-D., Wang, S.-Y., Liu, S.-J., et al. (2016) · BMC Psychiatry · doi:10.1186/s12888-016-1047-7 · Cited by 163 · see citing works
Resting-State Glutamate and GABA Concentrations Predict Task-Induced Deactivation in the Default Mode Network
Hu, Y., Chen, X., Gu, H., & Yang, Y. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1973-13.2013 · Cited by 167 · see citing works
Multivariate resting-state functional connectivity predicts response to cognitive behavioral therapy in obsessive-compulsive disorder
Reggente, N., Moody, T. D., Morfini, F., Sheen, C., Rissman, J., O’Neill, J., & Feusner, J. D. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1716686115 · Cited by 154 · see citing works
Distracted and down: neural mechanisms of affective interference in subclinical depression
Kaiser, R. H., Andrews-Hanna, J. R., Spielberg, J. M., Warren, S. L., Sutton, B. P., Miller, G. A., Heller, W., & Banich, M. T. (2015) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsu100 · Cited by 147 · see citing works
Reduced default mode network suppression during a working memory task in remitted major depression
Bartova, L., Meyer, B. M., Diers, K., Rabl, U., Scharinger, C., Popovic, A., Pail, G., Kalcher, K., Boubela, R. N., Huemer, J., et al. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.02.025 · Cited by 135 · see citing works
Divergent task-dependent functional connectivity of executive control and salience networks
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Mapping social reward and punishment processing in the human brain: A voxel-based meta-analysis of neuroimaging findings using the social incentive delay task
Martins, D., Rademacher, L., Gabay, A. S., Taylor, R., Richey, J. A., Smith, D. V., Goerlich, K. S., Nawijn, L., Cremers, H. R., Wilson, R., et al. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.12.034 · Cited by 119 · see citing works
Abnormal connectivity between the default mode and the visual system underlies the manifestation of visual hallucinations in Parkinson’s disease: a task-based fMRI study
Shine, J. M., Muller, A. J., O’Callaghan, C., Hornberger, M., Halliday, G. M., & Lewis, S. J. (2015) · npj Parkinson's Disease · doi:10.1038/npjparkd.2015.3 · Cited by 106 · see citing works
Evidence of successful modulation of brain activation and subjective experience during reappraisal of negative emotion in unmedicated depression
Dillon, D. G., & Pizzagalli, D. A. (2013) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2013.01.001 · Cited by 91 · see citing works
Modality-spanning deficits in attention-deficit/hyperactivity disorder in functional networks, gray matter, and white matter
Kessler, D., Angstadt, M., Welsh, R. C., & Sripada, C. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3156-14.2014 · Cited by 83 · see citing works
From State-to-Trait Meditation: Reconfiguration of Central Executive and Default Mode Networks
Bauer, C. C. C., Whitfield-Gabrieli, S., Díaz, J. L., Pasaye, E. H., & Barrios, F. A. (2019) · eneuro · doi:10.1523/eneuro.0335-18.2019 · Cited by 81 · see citing works
Neural correlates of affective and non-affective cognition in obsessive compulsive disorder: A meta-analysis of functional imaging studies
Rasgon, A., Lee, W. H., Leibu, E., Laird, A., Glahn, D., Goodman, W., & Frangou, S. (2017) · European Psychiatry · doi:10.1016/j.eurpsy.2017.08.001 · Cited by 73 · see citing works
Default-Mode Network Abnormalities in Pediatric Posttraumatic Stress Disorder
Patriat, R., Birn, R. M., Keding, T. J., & Herringa, R. J. (2016) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2016.01.010 · Cited by 78 · see citing works
Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder
Scheinost, D., Holmes, S. E., DellaGioia, N., Schleifer, C., Matuskey, D., Abdallah, C. G., Hampson, M., Krystal, J. H., Anticevic, A., & Esterlis, I. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.229 · Cited by 73 · see citing works
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Gray Matter and Functional Connectivity in Anterior Cingulate Cortex are Associated with the State of Mental Silence During Sahaja Yoga Meditation
Hernández, S. E., Barros-Loscertales, A., Xiao, Y., González-Mora, J. L., & Rubia, K. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2017.12.017 · Cited by 63 · see citing works
Regional GABA Concentrations Modulate Inter-network Resting-state Functional Connectivity
Chen, X., Fan, X., Hu, Y., Zuo, C., Whitfield-Gabrieli, S., Holt, D., Gong, Q., Yang, Y., Pizzagalli, D. A., Du, F., et al. (2019) · Cerebral Cortex · doi:10.1093/cercor/bhy059 · Cited by 62 · see citing works
Optogenetic stimulation of anterior insular cortex neurons in male rats reveals causal mechanisms underlying suppression of the default mode network by the salience network
Menon, V., Cerri, D., Lee, B., Yuan, R., Lee, S.-H., & Shih, Y.-Y. I. (2023) · Nature Communications · doi:10.1038/s41467-023-36616-8 · Cited by 53 · see citing works
Patterns of default mode network deactivation in obsessive compulsive disorder
Gonçalves, Ó. F., Soares, J. M., Carvalho, S., Leite, J., Ganho-Ávila, A., Fernandes-Gonçalves, A., Pocinho, F., Carracedo, A., & Sampaio, A. (2017) · Scientific Reports · doi:10.1038/srep44468 · Cited by 57 · see citing works
Alterations of agency in hypnosis: A new predictive coding model.
Martin, J.-R., & Pacherie, E. (2019) · Psychological Review · doi:10.1037/rev0000134 · Cited by 57 · see citing works
Neuronal dynamics of the default mode network and anterior insular cortex: intrinsic properties and modulation by salient stimuli
Chao, T.-H. H., Lee, B., Hsu, L.-M., Cerri, D. H., Zhang, W.-T., Wang, T.-W. W., Ryali, S., Menon, V., & Shih, Y.-Y. I. (2023) · Science Advances · doi:10.1126/sciadv.ade5732 · Cited by 49 · see citing works
Functional disruption of cerebello-thalamo-cortical networks in obsessive-compulsive disorder
Sha, Z., Edmiston, E. K., Versace, A., Fournier, J. C., Graur, S., Greenberg, T., Lima Santos, J. P., Chase, H. W., Stiffler, R. S., Bonar, L., et al. (2020) · Biological Psychiatry: Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2019.12.002 · Cited by 48 · see citing works
Distinct neurobiological signatures of brain connectivity in depression subtypes during natural viewing of emotionally salient films
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Neurochemical Modulation in Posteromedial Default-mode Network Cortex Induced by Transcranial Magnetic Stimulation
Vidal-Piñeiro, D., Martín-Trias, P., Falcón, C., Bargalló, N., Clemente, I. C., Valls-Solé, J., Junqué, C., Pascual-Leone, A., & Bartrés-Faz, D. (2015) · Brain Stimulation · doi:10.1016/j.brs.2015.04.005 · Cited by 49 · see citing works
Age‐related differences in working memory deficits during nicotine withdrawal
Falcone, M., Wileyto, E. P., Ruparel, K., Gerraty, R. T., LaPrate, L., Detre, J. A., Gur, R., Loughead, J., & Lerman, C. (2014) · Addiction Biology · doi:10.1111/adb.12051 · Cited by 48 · see citing works
Cortical organization of inhibition-related functions and modulation by psychopathology
Warren, S. L., Crocker, L. D., Spielberg, J. M., Engels, A. S., Banich, M. T., Sutton, B. P., Miller, G. A., & Heller, W. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00271 · Cited by 48 · see citing works
White matter network disruption and cognitive dysfunction in neuromyelitis optica spectrum disorder.
Cho, E. B., Han, C. E., Seo, S. W., Chin, J., Shin, J.-H., Cho, H.-J., Seok, J. M., Kim, S. T., Kim, B. J., Na, D. L., et al. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.01104 · Cited by 46 · see citing works
Brief Self-Compassion Training Alters Neural Responses to Evoked Pain for Chronic Low Back Pain: A Pilot Study
Berry, M. P., Lutz, J., Schuman-Olivier, Z., Germer, C., Pollak, S., Edwards, R. R., Gardiner, P., Desbordes, G., & Napadow, V. (2020) · Pain Medicine · doi:10.1093/pm/pnaa178 · Cited by 45 · see citing works
Neural connectivity moderates the association between sleep and impulsivity in adolescents
Tashjian, S. M., Goldenberg, D., & Galván, A. (2017) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2017.07.006 · Cited by 42 · see citing works
BOLD signal changes can oppose oxygen metabolism across the human cortex
Epp, S. M., Castrillón, G., Yuan, B., Andrews-Hanna, J., Preibisch, C., & Riedl, V. (2026) · Nature Neuroscience · doi:10.1038/s41593-025-02132-9 · Cited by 41 · see citing works
Functional imaging changes in the medial prefrontal cortex in adult ADHD
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Cortical phosphorylated α‐Synuclein levels correlate with brain wave spectra in Parkinson's disease
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Authors: Anticevic, A., Cole, M. W., Murray, J. D., Corlett, P. R., Wang, X.-J., & Krystal, J. H.
Affiliations: Yale University (US)
Washington University in St. Louis (US)
Yale New Haven Hospital (US)
Corresponding author: Anticevic, Alan
Krystal, John H.
ORCID: Anticevic, Alan
Cole, Michael W.
Murray, John D.
Corlett, Philip R.
Wang, Xiao-Jing
Krystal, John H.
Venue: Trends in Cognitive Sciences
Publisher: Elsevier BV
Published: 2012-12
Volume: 16
Issue: 12
Pages: 584-592
ISSN: 1364-6613 (ISSN-L)
DOI: 10.1016/j.tics.2012.10.008
PMC: PMC3501603
OpenAlex: W2145526417
Cited by: 978
References: 106
Citations by year: 2026: 71 · 2025: 61 · 2024: 58 · 2023: 65 · 2022: 91 · 2021: 97 · 2020: 79 · 2019: 79 · 2018: 67 · 2017: 61 · 2016: 78 · 2015: 70 · 2014: 69 · 2013: 30 · 2012: 1
FWCI: 4.16
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Cognitive Sciences (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (DP5OD01210901, DP5OD012109)
National Institute on Alcohol Abuse and Alcoholism (P50AA012870)
National Institute of Mental Health (MH096801, R01MH108590)
National Center for Research Resources (UL1RR024139)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Life Sciences › Neuroscience › Cognitive Neuroscience › Mind wandering and attention
Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Functions and Memory
Keywords: default mode network, goal-directed cognition, mind wandering, severe mental illness, attention, cognitive control
MeSH terms: Brain, Cognition, Cognition Disorders, Humans, Nerve Net

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The role of default network deactivation in cognition and disease

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