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Cited by 192Neural and Behavioral Psychology StudiesMemory and Neural MechanismsAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Amygdala–Prefrontal Cortex Functional Connectivity During Threat-Induced Anxiety and Goal Distraction

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Gold, Andrea L., Morey, Rajendra A., McCarthy, Gregory·2015·Biological Psychiatry
DOI 10.1016/j.biopsych.2014.03.030PMC PMC4349396
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Abstract

Background Anxiety produced by environmental threats can impair goal-directed processing and is associated with a range of psychiatric disorders, particularly when aversive events occur unpredictably. The prefrontal cortex (PFC) is thought to implement controls that minimize performance disruptions from threat-induced anxiety and goal distraction by modulating activity in regions involved in threat detection, such as the amygdala. The inferior frontal gyrus (IFG), orbitofrontal cortex (OFC), and ventromedial PFC (vmPFC) have been linked to the regulation of anxiety during threat exposure. We developed a paradigm to determine if threat-induced anxiety would enhance functional connectivity between the amygdala and IFG, OFC, and vmPFC. Methods Healthy adults performed a computer-gaming style task involving capturing prey and evading predators to optimize monetary rewards while exposed to the threat of unpredictable shock. Psychophysiological recording (n = 26) and functional magnetic resonance imaging scanning (n = 17) were collected during the task in separate cohorts. Task-specific changes in functional connectivity with the amygdala were examined using psychophysiological interaction analysis. Results Threat exposure resulted in greater arousal measured by increased skin conductance but did not influence performance (i.e., monetary losses or rewards). Greater functional connectivity between the right amygdala and bilateral IFG, OFC, vmPFC, anterior cingulate cortex, and frontopolar cortex was associated with threat exposure. Conclusions Exposure to unpredictable threat modulates amygdala-PFC functional connectivity that may help maintain performance when experiencing anxiety induced by threat. Our paradigm is well-suited to explore the neural underpinnings of the anxiety response to unpredictable threat in patients with various anxiety disorders.

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  • The ventral PFC is known to provide top-down, inhibitory control of the amygdala in the effective regulation of fear.

    “The ventral PFC is known to provide top-down, inhibitory control of the amygdala in the effective regulation of fear (Gold et al., 2015; Hermann et al., 2009; Phelps et al., 2004; Wager et al., 2008).”

    From Advancing the treatment of anxiety disorders in transition‐age youth: a review of the therapeutic effects of unconscious exposure. (2025) · cites this paper as Gold et al., 2015

    The Discussion describes the vmPFC as important to affect regulation and reports that its rodent homologue activates inhibitory networks in the amygdala during fear extinction. It also describes ventral PFC–amygdala interactions in humans, but the paper’s human findings concern functional connectivity; they do not establish the claimed top-down inhibitory control as a known mechanism of effective fear regulation. (LLM, conf=0.84)

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Authors
Gold, A. L., Morey, R. A., & McCarthy, G.
Affiliations
  • Yale University (US)
  • Duke University (US)
Corresponding author
McCarthy, Gregory
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2015-02
Volume
77
Issue
4
Pages
394-403
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2014.03.030
PMC
PMC4349396
OpenAlex
W2030679377
Cited by
192
References
27
Citations by year
2026: 15 · 2025: 17 · 2024: 13 · 2023: 9 · 2022: 16 · 2021: 23 · 2020: 18 · 2019: 14 · 2018: 21 · 2017: 22 · 2016: 15 · 2015: 6 · 2014: 3
FWCI
8.55
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DukeSpace (Duke University) (submittedVersion)
  • DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
Funders
National Institute of Neurological Disorders and Stroke (NS-41328)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords
amygdala, prefrontal cortex, functional connectivity, inferior frontal gyrus, orbitofrontal cortex, ventromedial prefrontal cortex, unpredictable threat, shock exposure, skin conductance, anxiety disorders
MeSH terms
Adult, Amygdala, Anxiety, Arousal, Brain Mapping, Electroshock, Female, Galvanic Skin Response, Goals, Humans, Magnetic Resonance Imaging, Male, Prefrontal Cortex, Young Adult

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