Contextual fear conditioning in humans: cortical–hippocampal and amygdala contributions
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Functional imaging studies of cued fear conditioning in humans have mostly confirmed findings in animals, but it is unclear whether the brain mechanisms that underlie contextual fear conditioning in animals are also preserved in humans. We investigated this issue using functional magnetic resonance imaging and virtual reality contexts. Subjects underwent differential context conditioning in which they were repeatedly exposed to two contexts (CXT+ and CXT-) in semirandom order, with contexts counterbalanced across participants. An unsignaled footshock was consistently paired with the CXT+, and no shock was ever delivered in the CXT-. Evidence for context conditioning was established using skin conductance and anxiety ratings. Consistent with animal models centrally implicating the hippocampus and amygdala in a network supporting context conditioning, CXT+ compared with CXT- significantly activated right anterior hippocampus and bilateral amygdala. In addition, context conditioning was associated with activation in posterior orbitofrontal cortex, medial dorsal thalamus, anterior insula, subgenual anterior cingulate, and parahippocampal, inferior frontal, and parietal cortices. Structural equation modeling was used to assess interactions among the core brain regions mediating context conditioning. The derived model indicated that medial amygdala was the source of key efferent and afferent connections including input from orbitofrontal cortex. These results provide evidence that similar brain mechanisms may underlie contextual fear conditioning across species.
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Similarly constructed VR stimuli are effective for studying context manipulations in the MRI environment.
“Previous research in our laboratory has shown that similarly constructed VR stimuli are effective for studying context manipulations in the MRI environment (Alvarez et al., 2008).”
From Phasic and sustained fear in humans elicits distinct patterns of brain activity (2011) · cites this paper as Alvarez et al., 2008
Transient activation in ventral amygdala/anterior hippocampus to unpredictable threat context onset provides further evidence that the amygdala and hippocampus play time-limited roles during sustained aversive contexts.
“Transient activation in ventral amygdala/anterior hippocampus to unpredictable threat context onset provides further evidence that the amygdala (Alvarez et al., 2008; Davis et al., 2010b) and hippocampus (Marschner et al., 2008) play time-limited roles during sustained aversive contexts.”
From Phasic and sustained fear in humans elicits distinct patterns of brain activity (2011) · cites this paper as Alvarez et al., 2008
Previous neuroimaging findings indicate that contextual fear conditioning elicits sustained activity in anterior insula.
“Previous neuroimaging findings indicating that contextual fear conditioning elicits sustained activity in anterior insula are consistent with this interpretation (Alvarez et al., 2008).”
From Phasic and sustained fear in humans elicits distinct patterns of brain activity (2011) · cites this paper as Alvarez et al., 2008
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- Authors
- Alvarez, R. P., Biggs, A., Chen, G., Pine, D. S., & Grillon, C.
- Affiliations
- National Institutes of Health (US)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-06-11
- Volume
- 28
- Issue
- 24
- Pages
- 6211-6219
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2475649
- OpenAlex
- W1990137058
- Cited by
- 325
- References
- 70
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 23 · 2023: 10 · 2022: 13 · 2021: 12 · 2020: 13 · 2019: 22 · 2018: 23 · 2017: 16 · 2016: 22 · 2015: 25 · 2014: 22 · 2013: 29 · 2012: 26
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (Z99 MH999999)
- National Institute of Mental Health
- 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
- contextual fear conditioning, hippocampus, amygdala, medial amygdala, orbitofrontal cortex, virtual reality, anterior cingulate cortex, thalamus, parahippocampal cortex, footshock
- MeSH terms
- Adult, Amygdala, Cerebral Cortex, Conditioning, Psychological, Fear, Female, Galvanic Skin Response, Hippocampus, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Models, Biological, Neural Pathways, Oxygen, Psychophysics, Time Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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