Overlapping neural systems mediating extinction, reversal and regulation of fear
Open accessAbstract
Learned fear is a process allowing quick detection of associations between cues in the environment and prediction of imminent threat. Adaptive function in a changing environment, however, requires organisms to quickly update this learning and have the ability to hinder fear responses when predictions are no longer correct. Here we focus on three strategies that can modify conditioned fear, namely extinction, reversal and regulation of fear, and review their underlying neural mechanisms. By directly comparing neuroimaging data from three separate studies that employ each strategy, we highlight overlapping brain structures that comprise a general circuitry in the human brain. This circuitry potentially enables the flexible control of fear, regardless of the particular task demands.
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Reappraisal does not rely on vmPFC-mediated emotional control.
“However, in contrast to several prominent theories, the present results indicate that reappraisal does not rely on vmPFCmediated emotional control (Ochsner andGross 2005, 2007;Schiller and Delgado 2010;Diekhof et al. 2011;Etkin et al. 2011), but instead may act though the lateral temporal cortex, an area associated with semantic and perceptual representation.”
From Cognitive Reappraisal of Emotion: A Meta-Analysis of Human Neuroimaging Studies (2014) · cites this paper as Schiller and Delgado 2010
In “A general neural mechanism for changing fear” (page unavailable), the review reports increased vmPFC responses when fear is regulated with cognitive strategies and suggests that dlPFC regulation may act through vmPFC connections. The citing sentence presents the absence of vmPFC-mediated control as its own result, in contrast to the theories it cites; Schiller and Delgado support the contrasting view, not that result. (LLM, conf=0.88)
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Experimental — accuracy not yet measuredThe null finding of no consistent vmPFC recruitment contradicts the hypothesis that vmPFC provides a necessary link by which frontal and parietal regions modulate emotion-related activity in the amygdala.
“This null finding contradicts the hypothesis that vmPFC provides a necessary link by which frontal and parietal regions modulate emotion-related activity in the amygdala (Ochsner andGross 2005, 2007;Schiller and Delgado 2010;Diekhof et al. 2011;Etkin et al. 2011).”
From Cognitive Reappraisal of Emotion: A Meta-Analysis of Human Neuroimaging Studies (2014) · cites this paper as Schiller and Delgado 2010
In “A general neural mechanism for changing fear” (page not provided), the review proposes that dlPFC might affect the amygdala indirectly through vmPFC connections. It does not establish vmPFC as a necessary link or extend that proposed pathway to parietal regions. The citing authors’ null finding is their own result, not a finding attributed to this source. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe implementation of reappraisal consistently activated domain-general cognitive control regions, including dmPFC, dlPFC, vlPFC, and posterior parietal lobe.
“In line with existing models, the implementation of reappraisal consistently activated domain-general cognitive control regions, including dmPFC, dlPFC, vlPFC, and posterior parietal lobe (Ochsner andGross 2005, 2008;Kalisch 2009;Schiller and Delgado 2010;Diekhof et al. 2011;Ochsner et al. 2012).”
From Cognitive Reappraisal of Emotion: A Meta-Analysis of Human Neuroimaging Studies (2014) · cites this paper as Schiller and Delgado 2010
The “Regulation of fear” section reports increased dlPFC activity during reappraisal and identifies the dlPFC with cognitive control. It does not identify dmPFC, vlPFC, or the posterior parietal lobe as consistently activated by reappraisal; it notes that the specific prefrontal areas recruited vary across studies. No page number is available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredConnectivity analyses, a meta-analysis by Diekhof et al. in 2011, and more recent dynamic causal modeling of cognitive reappraisal data support the hypothesis that cognitive control regions engage the vmPFC which then modulates the amygdala.
“Further, connectivity analyses [131, 132], a meta-analysis conducted by Diekhof et al. in 2011, and more recent dynamic causal modeling of cognitive reappraisal data [135], also support this hypothesis.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [132]
Findings from patients with autonomic failure and alexithymia primarily show quantitative changes in subjective experience, more consistent with a modulatory role of body feedback.
“Findings from patients with autonomic failure and alexithymia (119), although superficially supportive, primarily show quantitative changes in subjective experience, more consistent with a modulatory role of body feedback.”
From A higher-order theory of emotional consciousness (2017) · cites this paper as [119]
The Regulation of fear section discusses cognitive strategies and changes in emotional responses, while the Fear reversal section mentions physiological measures of fear. Neither addresses patients with autonomic failure or alexithymia, quantitative changes in their subjective experience, or a modulatory role for body feedback. Searches for those terms found no relevant passage in our copy. (LLM, conf=0.75)
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References 102 · Cited by 294
- Authors
- Schiller, D., & Delgado, M. R.
- Affiliations
- New York University (US)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Schiller, Daniela
- Venue
- Trends in Cognitive Sciences
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 14
- Issue
- 6
- Pages
- 268-276
- ISSN
- 1364-6613 (ISSN-L)
- PMC
- PMC3848321
- OpenAlex
- W2110208797
- Cited by
- 294
- References
- 102
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 10 · 2023: 14 · 2022: 19 · 2021: 27 · 2020: 12 · 2019: 17 · 2018: 31 · 2017: 13 · 2016: 30 · 2015: 25 · 2014: 24 · 2013: 24 · 2012: 16
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Trends in Cognitive Sciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R21MH072279)
- National Institute on Drug Abuse (R01DA027764)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- learned fear, fear extinction, fear regulation, fear conditioning, neural circuits, threat prediction, neural mechanisms
- MeSH terms
- Animals, Brain, Brain Mapping, Conditioning, Classical, Extinction, Psychological, Fear, Humans, Neural Pathways
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