Cited by 241Neural and Behavioral Psychology StudiesMemory and Neural MechanismsAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

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Uncertainty during Anticipation Modulates Neural Responses to Aversion in Human Insula and Amygdala

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Sarinopoulos, I., Grupe, D. W., Mackiewicz, K. L., Herrington, J. D., Lor, M., Steege, E. E., Nitschke, J. B.·2010·Cerebral Cortex

DOI 10.1093/cercor/bhp155PMC PMC2837092

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Abstract

Uncertainty about potential negative future outcomes can cause stress and is a central feature of anxiety disorders. The stress and anxiety associated with uncertain situations may lead individuals to overestimate the frequency with which uncertain cues are followed by negative outcomes, an example of covariation bias. Using functional magnetic resonance imaging, we found that uncertainty-related expectations modulated neural responses to aversion. Insula and amygdala responses to aversive pictures were larger after an uncertain cue (that preceded aversive or neutral pictures) than a certain cue (that always preceded aversive pictures). Anticipatory anterior cingulate cortex (ACC) activity elicited by the cues was inversely associated with the insula and amygdala responses to aversive pictures following the cues. Nearly 75% of subjects overestimated the frequency of aversive pictures following uncertain cues, and ACC and insula activity predicted this uncertainty-related covariation bias. Findings provide the first evidence of the brain mechanisms of covariation bias and highlight the temporal dynamics of ACC, insula, and amygdala recruitment for processing aversion in the context of uncertainty.

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Authors: Sarinopoulos, I., Grupe, D. W., Mackiewicz, K. L., Herrington, J. D., Lor, M., Steege, E. E., & Nitschke, J. B.
Affiliations: Michigan State University (US)
University of Wisconsin–Madison (US)
University of Colorado Boulder (US)
Children's Hospital of Philadelphia (US)
Columbia University (US)
West Virginia University (US)
ORCID: Sarinopoulos, I.
Grupe, D. W.
Herrington, J. D.
Venue: Cerebral Cortex
Publisher: Oxford University Press (OUP)
Published: 2009-08-13
Volume: 20
Issue: 4
Pages: 929-940
ISSN: 1047-3211 (ISSN-L)
1460-2199
DOI: 10.1093/cercor/bhp155
PMC: PMC2837092
OpenAlex: W2138497717
Cited by: 241
References: 114
Citations by year: 2026: 5 · 2025: 10 · 2024: 9 · 2023: 9 · 2022: 18 · 2021: 15 · 2020: 11 · 2019: 9 · 2018: 22 · 2017: 14 · 2016: 18 · 2015: 18 · 2014: 21 · 2013: 20 · 2012: 17
FWCI: 6.61
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Cerebral Cortex (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Waisman Center (HD03352)
National Institutes of Health (5k02mh082130-05)
National Institute of Mental Health (K02‑MH082130, P30-HD03352, R01MH074847, K08MH063984, R01-MH74847, K08-MH63984)
National Institute of Child Health and Human Development (P30HD03352, HD03352)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD03352., P30HD003352)
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: uncertainty, anticipation, aversion, insula, amygdala, anterior cingulate cortex, anxiety, stress, aversive stimuli, expectations, temporal dynamics of neural responses
MeSH terms: Affect, Amygdala, Avoidance Learning, Brain Mapping, Cues, Female, Gyrus Cinguli, Humans, Image Processing, Computer-Assisted, Functional Laterality, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Oxygen, Photic Stimulation, Uncertainty, Young Adult

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Uncertainty during Anticipation Modulates Neural Responses to Aversion in Human Insula and Amygdala

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