ABERRANT AMYGDALA-FRONTAL CORTEX CONNECTIVITY DURING PERCEPTION OF FEARFUL FACES AND AT REST IN GENERALIZED SOCIAL ANXIETY DISORDER: Research Article: Amygdala-Frontal Connectivity in gSAD
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BACKGROUND: Generalized social anxiety disorder (gSAD) is characterized by exaggerated amygdala reactivity to social signals of threat, but if and how the amygdala interacts with functionally and anatomically connected prefrontal cortex (PFC) remains largely unknown. Recent evidence points to aberrant amygdala connectivity to medial PFC in gSAD at rest, but it is difficult to attribute functional relevance without the context of threat processing. Here, we address this by studying amygdala-frontal cortex connectivity during viewing of fearful faces and at rest in gSAD patients. METHODS: Twenty patients with gSAD and 17 matched healthy controls (HCs) participated in functional magnetic resonance imaging of an emotional face matching task and a resting state task. Functional connectivity and psychophysiological interaction analysis were used to assess amygdala connectivity. RESULTS: Compared to HCs, gSAD patients exhibited less connectivity between amygdala and the rostral anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) while viewing fearful faces. gSAD patients also showed less connectivity between amygdala and rostral ACC at rest in the absence of fearful faces. DLPFC connectivity was negatively correlated with LSASFear (where LSAS is Liebowitz Social Anxiety Scale). CONCLUSIONS: Task and rest paradigms provide unique and important information about discrete and overlapping functional networks. In particular, amygdala coupling to DLPFC may be a phasic abnormality, emerging only in the presence of a social predictor of threat, whereas amygdala coupling to the rostral ACC may reflect both phasic and tonic abnormalities. These findings prompt further studies to better delineate intrinsic and externally evoked brain connectivity in anxiety and depression in relation to amygdala dysfunction.
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Decreased connectivity between the amygdala and DLPFC has also been found in social anxiety disorders and other stress-related conditions, suggesting it is not a unique feature of major depressive disorder.
“The decreased connectivity between amygdala and DLPFC has also been found in social anxiety disorders and other stress-related conditions, suggesting it is not a unique feature of MDD (Prater et al., 2013).”
From Social functioning in major depressive disorder (2016) · cites this paper as Prater et al., 2013
Prior studies have shown reduced or disrupted amygdala-insula and amygdala-dACC connectivity to threatening faces in individuals with GSAD.
“The current pattern of results is noteworthy given that prior studies have shown reduced or disrupted amygdalainsula and amygdala-dACC connectivity to threatening faces in individuals with GSAD (Prater et al, 2013).”
From Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder (2015) · cites this paper as Prater et al, 2013
The finding of decreased amygdala-mPFC/rACC connectivity in GSAD is consistent with two prior papers from independent cohorts (Hahn et al, 2011; Prater et al, 2013).
“These findings are consistent with two prior papers from independent cohorts (Hahn et al, 2011;Prater et al, 2013).”
From Modulation of Resting-State Amygdala-Frontal Functional Connectivity by Oxytocin in Generalized Social Anxiety Disorder (2014) · cites this paper as Prater et al, 2013
Generalized social anxiety disorder (GSAD) is characterized by aberrant patterns of amygdala-frontal connectivity to social signals of threat and at rest.
“Generalized social anxiety disorder (GSAD) is characterized by aberrant patterns of amygdala-frontal connectivity to social signals of threat and at rest.”
From Modulation of Resting-State Amygdala-Frontal Functional Connectivity by Oxytocin in Generalized Social Anxiety Disorder (2014) · cites this paper as Prater et al, 2013
OXT may have a role in ameliorating abnormalities associated with emotion regulation pathways in GSAD observed at rest, suggesting a neural mechanism by which OXT may exert its effects acutely.
“Our findings of enhanced connectivity suggest that OXT may have a role in ameliorating abnormalities associated with emotion regulation pathways in GSAD observed at rest (Prater et al, 2013), suggesting a neural mechanism by which OXT may exert its effects acutely.”
From Modulation of Resting-State Amygdala-Frontal Functional Connectivity by Oxytocin in Generalized Social Anxiety Disorder (2014) · cites this paper as Prater et al, 2013
Reduced left amygdala-rACC connectivity in GSAD patients at rest may indicate an abnormal threat-emotion processing circuit and may be a marker of the pathophysiology of GSAD at rest and during threat perception.
“The reduced left amygdala-rACC connectivity we found in GSAD patients at resting state may indicate an abnormal threat-emotion processing circuit in these patients at baseline and may be a marker of the pathophysiology of GSAD at rest and during threat perception (Prater et al, 2013).”
From Modulation of Resting-State Amygdala-Frontal Functional Connectivity by Oxytocin in Generalized Social Anxiety Disorder (2014) · cites this paper as Prater et al, 2013
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- Authors
- Prater, K. E., Hosanagar, A., Klumpp, H., Angstadt, M., & Luan Phan, K.
- Affiliations
- University of Michigan (US)
- University of Illinois Chicago (US)
- Venue
- Depression and Anxiety
- Publisher
- Hindawi Limited
- Published
- 2012-11-26
- Volume
- 30
- Issue
- 3
- Pages
- 234-241
- ISSN
- 1091-4269 (ISSN-L)
- PMC
- PMC3987867
- OpenAlex
- W1553827588
- Cited by
- 194
- References
- 38
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 14 · 2023: 8 · 2022: 15 · 2021: 19 · 2020: 12 · 2019: 14 · 2018: 10 · 2017: 15 · 2016: 20 · 2015: 21 · 2014: 26 · 2013: 8
- FWCI
- 23.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Depression and Anxiety (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institutes of Health (5t32mh014279-33)
- National Institute of Mental Health (T32-MH-014279, 5T32MH014279, K23MH093679, K23MH076198)
- National Institute of Neurological Disorders and Stroke (T32NS076401)
- National Center for Research Resources (UL1RR024986)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- generalized social anxiety disorder, amygdala, prefrontal cortex, fearful faces, rostral anterior cingulate cortex, dorsolateral prefrontal cortex, resting-state functional connectivity, threat processing, functional connectivity, psychophysiological interaction
- MeSH terms
- Adult, Amygdala, Face, Facial Expression, Fear, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Net, Neuropsychological Tests, Phobic Disorders, Rest, Social Perception, Prefrontal Cortex, Young Adult
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