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Uncertainty during Anticipation Modulates Neural Responses to Aversion in Human Insula and Amygdala
Open accessAbstract
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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In the citing paper
“AIC responses to expected aversive stimuli are larger if expectations are uncertain”
From An Interoceptive Predictive Coding Model of Conscious Presence (2012) · cites this paper as Sarinopoulos et al., 2010
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In the citing paper
“In their study, insula and amygdala responses were larger after an uncertain cue than a certain cue.”
From Extension of the Transdiagnostic Model to Focus on Intolerance of Uncertainty: A Review of the Literature and Implications for Treatment (2014) · cites this paper as Sarinopoulos et al. (2010)
In the citing paper
“Studies of instructed fear that have examined neural activity underlying both anticipation of and responses to briefly presented aversive pictures have also revealed dorsal amygdala activation (Mackiewicz et al., 2006; Nitschke et al., 2006), provided that the aversive events are predictably signaled (Sarinopoulos et al., 2010).”
From Phasic and sustained fear in humans elicits distinct patterns of brain activity (2011) · cites this paper as Sarinopoulos et al., 2010
In the citing paper
“Particularly, sources in the insula and amygdala, known to process subjective salience (Davis, & Whalen, 2001;Straube, & Miltner, 2011), corroborate imaging results, specifically uncertainty-related amygdalar hyperactivity in pediatric anxiety (Sarinopoulos et al., 2010;Williams et al., 2015).”
From Uncertainty increases neural indices of attention in obsessive-compulsive disorder (2017) · cites this paper as Sarinopoulos et al., 2010
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Metadata
- 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)
- 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
- 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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