Aberrant spontaneous and task-dependent functional connections in the anxious brain
Open accessAbstract
A number of brain regions have been implicated in the anxiety disorders, yet none of these regions in isolation has been distinguished as the sole or discrete site responsible for anxiety disorder pathology. Therefore, the identification of dysfunctional neural networks as represented by alterations in the temporal correlation of blood-oxygen level dependent (BOLD) signal across several brain regions in anxiety disorders has been increasingly pursued in the past decade. Here, we review task-independent (e.g., resting state) and task-induced functional connectivity magnetic resonance imaging (fcMRI) studies in the adult anxiety disorders (including trauma- and stressor-related and obsessive compulsive disorders). The results of this review suggest that anxiety disorder pathophysiology involves aberrant connectivity between amygdala-frontal and frontal-striatal regions, as well as within and between canonical "intrinsic" brain networks - the default mode and salience networks, and that evidence of these aberrations may help inform findings of regional activation abnormalities observed in the anxiety disorders. Nonetheless, significant challenges remain, including the need to better understand mixed findings observed using different methods (e.g., resting state and task-based approaches); the need for more developmental work; the need to delineate disorder-specific and transdiagnostic fcMRI aberrations in the anxiety disorders; and the need to better understand the clinical significance of fcMRI abnormalities. In meeting these challenges, future work has the potential to elucidate aberrant neural networks as intermediate, brain-based phenotypes to predict disease onset and progression, refine diagnostic nosology, and ascertain treatment mechanisms and predictors of treatment response across anxiety, trauma-related and obsessive compulsive disorders.
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The salience network supports automatic threat evaluation/detection and spans amygdala/insula/frontal regions.
“Such research links anxiety with dysfunctional interactions among multiple brain regions, including the salience network (supporting automatic threat evaluation/detection, and spanning amygdala/insula/frontal regions) and executive control network (supporting goal-directed activity, and spanning frontal/parietal regions) [110-115].”
From Anxiety and Threat-Related Attention: Cognitive-Motivational Framework and Treatment (2018) · cites this paper as [115]
Anxiety and ABs may emerge from an imbalance between threat salience evaluation and cognitive control processes, described at both cognitive and neural network levels.
“Anxiety and ABs may emerge from an imbalance between threat salience evaluation and cognitive control processes, described at both cognitive and neural network levels [115,118-121].”
From Anxiety and Threat-Related Attention: Cognitive-Motivational Framework and Treatment (2018) · cites this paper as [115]
Anxiety is linked with dysfunctional interactions among multiple brain regions, including the salience network and executive control network.
“Such research links anxiety with dysfunctional interactions among multiple brain regions, including the salience network (supporting automatic threat evaluation/detection, and spanning amygdala/insula/frontal regions) and executive control network (supporting goal-directed activity, and spanning frontal/parietal regions) [110-115].”
From Anxiety and Threat-Related Attention: Cognitive-Motivational Framework and Treatment (2018) · cites this paper as [115]
The executive control network supports goal-directed activity and spans frontal/parietal regions.
“Such research links anxiety with dysfunctional interactions among multiple brain regions, including the salience network (supporting automatic threat evaluation/detection, and spanning amygdala/insula/frontal regions) and executive control network (supporting goal-directed activity, and spanning frontal/parietal regions) [110-115].”
From Anxiety and Threat-Related Attention: Cognitive-Motivational Framework and Treatment (2018) · cites this paper as [115]
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- Authors
- MacNamara, A., DiGangi, J., & Phan, K. L.
- Affiliations
- University of Illinois Chicago (US)
- Corresponding author
- MacNamara, Annmarie
- Venue
- Biological Psychiatry Cognitive Neuroscience and Neuroimaging
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 1
- Issue
- 3
- Pages
- 278-287
- ISSN
- 2451-9022 (ISSN-L)
- PMC
- PMC4851245
- OpenAlex
- W2219484125
- Cited by
- 34
- References
- 138
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 4
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry Cognitive Neuroscience and Neuroimaging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (K23MH105553, R01MH101497)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- anxiety disorders, functional connectivity, resting-state functional connectivity, default mode network, salience network, trauma- and stressor-related disorders, obsessive-compulsive disorder, treatment response prediction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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