Patients with dorsolateral prefrontal cortex lesions are capable of discriminatory threat learning but appear impaired in cognitive regulation of subjective fear
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Humans are able to cognitively regulate emotions by changing their thoughts. Neuroimaging studies show correlations between dorsolateral prefrontal cortex (dlPFC) activity and cognitive regulation of emotions. Here our objective was to investigate whether dlPFC damage is associated with impaired cognitive regulation of emotion. We therefore tested the ability of patients with dlPFC lesions (N = 6) and matched control participants (N = 19) to utilize a laboratory version of cognitive regulation training (CRT) to regulate subjective fear and autonomic threat responses following Pavlovian threat conditioning. We found that patients with dlPFC lesions were able to acquire conditioned threat but seemed impaired in their ability to utilize CRT to cognitively regulate subjective fear to a threatening stimulus. Despite inclusion of a limited number of lesion patients, our results suggest that the dlPFC is important for the cognitive regulation of subjective fear.
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One lesion study supports a role of the dlPFC in cognitive reappraisal.
“Although there do not seem to be structural changes related to the successful cognitive reappraisal, there is one lesion study [140] that supports a role of the dlPFC in cognitive reappraisal.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [140]
Individuals with dlPFC lesions showed impaired ability to reappraise threat conditioned stimuli as indexed by poorer subjective fear outcomes, compared to matched controls.
“This study examined individuals with dlPFC lesions and found that they showed impaired ability to reappraise threat conditioned stimuli as indexed by poorer subjective fear outcomes, compared to matched controls.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [140]
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Shi, H., Liu, L., Chen, X., Luo, W., & Luo, Y. (2025) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-025-01368-z
Veinot, J., & Hashmi, J. A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.28.708768
- Authors
- Kroes, M. C. W., Dunsmoor, J. E., Hakimi, M., Oosterwaal, S., NYU PROSPEC collaboration, Meager, M. R., & Phelps, E. A.
- Affiliations
- Radboud University Nijmegen (NL)
- The University of Texas at Austin (US)
- New York University (US)
- NYU Langone Health (US)
- Harvard University (US)
- Corresponding author
- Kroes, Marijn C W
- Venue
- Social Cognitive and Affective Neuroscience
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-05-23
- Volume
- 14
- Issue
- 6
- Pages
- 601-612
- ISSN
- 1749-5016 (ISSN-L)
- 1749-5024
- PMC
- PMC6688449
- OpenAlex
- W2945369047
- Cited by
- 46
- References
- 44
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 12 · 2023: 5 · 2022: 7 · 2021: 8 · 2020: 3 · 2019: 2
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Social Cognitive and Affective Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- NIHM (5R01MH097085-03)
- National Institute of Mental Health (K99/R00)
- Society in Science—Branco Weiss fellowship
- H2020 Marie Sklodowska-Curie
- 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
- dorsolateral prefrontal cortex, cognitive emotion regulation, subjective fear, threat learning, brain lesions
- MeSH terms
- Adult, Aged, Cognition, Conditioning, Classical, Discrimination Learning, Fear, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Prefrontal Cortex
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