Human Fear Conditioning and Extinction in Neuroimaging: A Systematic Review
Open accessAbstract
Fear conditioning and extinction are basic forms of associative learning that have gained considerable clinical relevance in enhancing our understanding of anxiety disorders and facilitating their treatment. Modern neuroimaging techniques have significantly aided the identification of anatomical structures and networks involved in fear conditioning. On closer inspection, there is considerable variation in methodology and results between studies. This systematic review provides an overview of the current neuroimaging literature on fear conditioning and extinction on healthy subjects, taking into account methodological issues such as the conditioning paradigm. A Pubmed search, as of December 2008, was performed and supplemented by manual searches of bibliographies of key articles. Two independent reviewers made the final study selection and data extraction. A total of 46 studies on cued fear conditioning and/or extinction on healthy volunteers using positron emission tomography or functional magnetic resonance imaging were reviewed. The influence of specific experimental factors, such as contingency and timing parameters, assessment of conditioned responses, and characteristics of conditioned and unconditioned stimuli, on cerebral activation patterns was examined. Results were summarized descriptively. A network consisting of fear-related brain areas, such as amygdala, insula, and anterior cingulate cortex, is activated independently of design parameters. However, some neuroimaging studies do not report these findings in the presence of methodological heterogeneities. Furthermore, other brain areas are differentially activated, depending on specific design parameters. These include stronger hippocampal activation in trace conditioning and tactile stimulation. Furthermore, tactile unconditioned stimuli enhance activation of pain related, motor, and somatosensory areas. Differences concerning experimental factors may partly explain the variance between neuroimaging investigations on human fear conditioning and extinction and should, therefore, be taken into serious consideration in the planning and the interpretation of research projects.
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Fear-related neural networks include the amygdala as well as middle and anterior parts of the cingulate cortex.
“These networks include the amygdala as well as middle and anterior parts of the cingulate cortex”
From Oxytocin Facilitates Pavlovian Fear Learning in Males (2016) · cites this paper as Sehlmeyer et al, 2009
The anterior cingulate cortex (ACC) has a crucial role within a general neural fear circuit and within Pavlovian fear conditioning.
“previous findings showing that the ACC has a crucial role within a general neural fear circuit (Hariri et al, 2003) as well as within the framework of Pavlovian fear conditioning (see reviews by Milad et al, 2007;Sehlmeyer et al, 2009).”
From Oxytocin Facilitates Pavlovian Fear Learning in Males (2016) · cites this paper as Sehlmeyer et al, 2009
In spite of methodological diversity across individual fear-conditioning studies, these studies consistently evoke a common large-scale brain activation response.
“We therefore conclude that in spite of the considerable methodological diversity that exists across individual fearconditioning studies, these studies consistently evoke a common large-scale brain activation response.17”
From Neural signatures of human fear conditioning: an updated and extended meta-analysis of fMRI studies (2016) · cites this paper as [17]
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- Authors
- Sehlmeyer, C., Schöning, S., Zwitserlood, P., Pfleiderer, B., Kircher, T., Arolt, V., & Konrad, C.
- Affiliations
- University of Münster (DE)
- Philipps University of Marburg (DE)
- Corresponding author
- Konrad, Carsten
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-06-10
- Volume
- 4
- Issue
- 6
- Pages
- e5865
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2692002
- OpenAlex
- W2064135174
- Cited by
- 543
- References
- 123
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 18 · 2023: 23 · 2022: 18 · 2021: 31 · 2020: 28 · 2019: 30 · 2018: 33 · 2017: 34 · 2016: 46 · 2015: 45 · 2014: 45 · 2013: 63 · 2012: 37
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- fear conditioning, fear extinction, associative learning, anxiety disorders, amygdala, insula, anterior cingulate cortex, hippocampus, trace conditioning, methodological heterogeneity, brain activation patterns
- MeSH terms
- Adult, Amygdala, Avoidance Learning, Brain, Brain Mapping, Conditioning, Psychological, Electrophysiology, Extinction, Psychological, Fear, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Middle Aged
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