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Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus
Open accessAbstract
To better understand intrinsic brain connections in major depression, we used a neuroimaging technique that measures resting state functional connectivity using functional MRI (fMRI). Three different brain networks—the cognitive control network, default mode network, and affective network—were investigated. Compared with controls, in depressed subjects each of these three networks had increased connectivity to the same bilateral dorsal medial prefrontal cortex region, an area that we term the dorsal nexus. The dorsal nexus demonstrated dramatically increased depression-associated fMRI connectivity with large portions of each of the three networks. The discovery that these regions are linked together through the dorsal nexus provides a potential mechanism to explain how symptoms of major depression thought to arise in distinct networks—decreased ability to focus on cognitive tasks, rumination, excessive self-focus, increased vigilance, and emotional, visceral, and autonomic dysregulation—could occur concurrently and behave synergistically. It suggests that the newly identified dorsal nexus plays a critical role in depressive symptomatology, in effect “hot wiring” networks together; it further suggests that reducing increased connectivity of the dorsal nexus presents a potential therapeutic target.
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“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 [57]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“According to the dorsal nexus hypothesis, reducing hyperactive dorsolateral PFC reactivity to negative stimuli in remission may restore emotion regulation capacity.”
From Static and treatment-responsive brain biomarkers of depression relapse vulnerability following prophylactic psychotherapy: Evidence from a randomized control trial (2022) · cites this paper as Sheline et al., 2010
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Abnormality of the default mode network in depression is reported in several previous studies (Greicius et al., 2007;Bluhm et al., 2009;Sheline et al., 2010;Zhou et al., 2010b).”
From Identifying major depression using whole-brain functional connectivity: a multivariate pattern analysis (2012) · cites this paper as Sheline et al., 2010
The cited source says what the claim attributes to it.
In the citing paper
“Abnormal resting-state connectivity of the subgenual cingulate cortex (sgACC) was previously found in cross-sectional studies of MDD, suggesting its potential pathophysiological importance.”
From A novel resting-state functional magnetic resonance imaging signature of resilience to recurrent depression (2017) · cites this paper as Sheline et al. 2010
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“Recent findings suggested that the DMN has altered resting state functional connectivity between networks when depressed patients were compared to healthy participants [20].”
From State and training effects of mindfulness meditation on brain networks reflect neuronal mechanisms of its antidepressant effect (2016) · cites this paper as [20]
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“Sheline and colleagues [20] reported that such hyperconnectivity in the DMN exists for MDD; and, in their study, they highlighted the importance of abnormal hyperconnectivity of a “dorsal nexus.””
From State and training effects of mindfulness meditation on brain networks reflect neuronal mechanisms of its antidepressant effect (2016) · cites this paper as [20]
In the citing paper
“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 [217]
In the citing paper
“In line with these results both task-based and resting state studies reported abnormal functional connectivity within the frontolimbic network (4,6,17,18,55-57).”
From Relation Between Structural and Functional Connectivity in Major Depressive Disorder (2013) · cites this paper as [56]
In the citing paper
“Anterior cingulate cortex, as a critical brain region in emotion processing, has been implicated as a focus of dysfunction in depression (Greicius et al., 2007;Sheline et al., 2010).”
From Identifying major depression using whole-brain functional connectivity: a multivariate pattern analysis (2012) · cites this paper as Sheline et al., 2010
In the citing paper
“In addition, the altered connectivity between temporal poles and the parahippocampal gyrus, as well as the basal ganglia and orbitofrontal cortex, may reflect dysfunctions of visceral monitoring, which is compromised in depression (Sheline et al., 2010).”
From Identifying major depression using whole-brain functional connectivity: a multivariate pattern analysis (2012) · cites this paper as Sheline et al., 2010
In the citing paper
“What is suggested is that a potential mechanism of action of rTMS to dmPFC is increased influence of cognitive control networks over thalamic and striatal regions, possibly linked with improved facilitation of goal-directed behavior (Corbetta and Shulman, 2002; Price and Drevets, 2010; Sheline et al, 2010).”
From Resting-state cortico-thalamic-striatal connectivity predicts response to dorsomedial prefrontal rTMS in major depressive disorder (2014) · cites this paper as Sheline et al, 2010
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Metadata
- Authors
- Sheline, Y. I., Price, J. L., Yan, Z., & Mintun, M. A.
- Affiliations
- Departments of aPsychiatry,
- Washington University in St. Louis (US)
- Radiology,
- ORCID
- Sheline, Yvette I.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-06
- Volume
- 107
- Issue
- 24
- Pages
- 11020-11025
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2890754
- OpenAlex
- W2146146069
- Semantic Scholar
- b53712da3f27fd60407bee652706e0add8893b5b
- Cited by
- 1,196
- References
- 37
- Citations by year
- 2026: 65 · 2025: 65 · 2024: 44 · 2023: 67 · 2022: 64 · 2021: 98 · 2020: 74 · 2019: 81 · 2018: 98 · 2017: 84 · 2016: 100 · 2015: 85 · 2014: 80 · 2013: 89 · 2012: 67
- FWCI
- 36.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (K24MHO79510)
- National Institute of Mental Health (K24 MHO79510, R01 MH64821, R01MH064821, K24MH079510)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- major depressive disorder, resting-state functional connectivity, dorsomedial prefrontal cortex, cognitive control network, default mode network, affective networks, intrinsic brain networks, rumination, emotional dysregulation, therapeutic target
- MeSH terms
- Adult, Affect, Cognition, Depressive Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Models, Neurological, Nerve Net, Rest, Case-Control Studies, Prefrontal Cortex
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