Depressive rumination, the default-mode network, and the dark matter of clinical neuroscience
Open accessAbstract
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.
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Decreased rumination might mediate the therapeutic effects of mindfulness and psychedelics, as excessive rumination and DMN hyperactivity have been linked in depression.
“Decreased rumination might mediate the aforementioned therapeutic effects, as excessive rumination and DMN hyperactivity have been crucially linked in depression (119).”
From Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy (2021) · cites this paper as [119]
The DMN in MDD section links greater DMN dominance with maladaptive rumination in people with MDD, supporting that part of the citation. But the Abstract and “Integrating the data” explicitly say that DMN nodes have not shown reliable overactivation in MDD; the abnormality is increased connectivity between the DMN and sgPFC, not DMN hyperactivity. The sentence’s proposed therapeutic mechanism is the citing authors’ inference, not a finding attributed to this source. (LLM, conf=0.86)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredCore intrinsic connectivity networks (default-mode, salience, and central executive networks) are dysfunctional in individuals with internalizing disorders.
“The core intrinsic connectivity networks (core-ICNs), encompassing the default-mode network (DMN), salience network (SN) and central executive network (CEN), have been shown to be dysfunctional in individuals with internalizing disorders (IDs, e.g. major depressive disorder, MDD; generalized anxiety disorder, GAD; social anxiety disorder, SOC).”
From Infraslow closed-loop brain training for anxiety and depression (ISAD): a protocol for a randomized, double-blind, sham-controlled pilot trial in adult females with internalizing disorders (2022) · cites this paper as [33]
The ‘DMN in MDD > Resting-state fMRI’ section reports increased connectivity between the default-mode network and several brain regions in major depressive disorder. The paper describes the salience network in ‘Introduction > Properties of the DMN,’ but the cited passages do not establish that the salience and central executive networks are dysfunctional across MDD, generalized anxiety disorder, and social anxiety disorder. No page numbers are provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMaladaptive rumination has 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 [55]
While the thalamus is itself not described as a part of the DMN, patients with MDD seem to have significantly higher connectivity to the DMN compared to controls.
“While the thalamus is itself not described as a part of the DMN, patients with MDD seem to have significantly higher connectivity to the DMN compared to controls (54, 55).”
From SSRI Treatment Response Prediction in Depression Based on Brain Activation by Emotional Stimuli (2020) · cites this paper as [55]
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- Authors
- Hamilton, J. P., Farmer, M., Fogelman, P., & Gotlib, I. H.
- Affiliations
- Laureate Institute for Brain Research (US)
- University of Tennessee at Knoxville (US)
- Stanford University (US)
- Corresponding author
- Hamilton, J. Paul
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 78
- Issue
- 4
- Pages
- 224-230
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4524294
- OpenAlex
- W2055862036
- Cited by
- 952
- References
- 74
- Citations by year
- 2026: 136 · 2025: 111 · 2024: 78 · 2023: 80 · 2022: 89 · 2021: 117 · 2020: 113 · 2019: 74 · 2018: 58 · 2017: 41 · 2016: 45 · 2015: 8
- FWCI
- 4.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH74849, R01MH074849)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- depressive rumination, default mode network, major depressive disorder, subgenual prefrontal cortex, functional connectivity, regional cerebral blood flow, self-referential processing, withdrawal behavior
- MeSH terms
- Adult, Aged, Brain, Brain Mapping, Major Depressive Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Models, Neurological, Nerve Net, Neurosciences, Thinking, Prefrontal Cortex, Young Adult
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