Context conditioning and extinction in humans: differential contribution of the hippocampus, amygdala and prefrontal cortex
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Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty-one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS- was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS- in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context-specificity of extinction learning.
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Connectivity analyses have demonstrated functional coupling between the mPFC and amygdala during extinction learning, and vmPFC and amygdala during extinction recall.
“Connectivity analyses have demonstrated functional coupling between the mPFC and amygdala during extinction learning [107], and vmPFC and amygdala during extinction recall [89, 108].”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [107]
Functional connectivity analyses suggest coupling of the PFC and hippocampus during contextual extinction learning and recall.
“Importantly, functional connectivity analyses also suggest coupling of the PFC and hippocampus during contextual extinction learning [107] and recall [89].”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [107]
The dACC is important for both extinction learning and emotion regulation through cognitive reappraisal, and is hypoactivated during emotion regulation in GAD.
“The dACC is a region previously identified as important for both extinction learning (Lang et al., 2009; Maier et al., 2012) and emotion regulation through cognitive reappraisal (Ochsner et al., 2002, 2004), and a region previously shown to be hypoactivated during emotion regulation in GAD (Blair et al., 2012).”
From Neural correlates of emotion acceptance<i>vs</i>worry or suppression in generalized anxiety disorder (2017) · cites this paper as Lang et al., 2009
Increased late-phase dACC activation in the acceptance condition was found in regions that directly overlap with those reported in the extinction of contextual fear, and in particular the early stages of within-session extinction.
“Increased late-phase dACC activation in the acceptance condition was found in regions that directly overlap with those reported in the extinction of contextual fear, and in particular the early stages of within-session extinction (Lang et al., 2009; Etkin et al., 2011).”
From Neural correlates of emotion acceptance<i>vs</i>worry or suppression in generalized anxiety disorder (2017) · cites this paper as Lang et al., 2009
Studies examining the extinction of contextual fear have implicated a larger role for the dACC.
“Although an emphasis has been placed on the role of subgenual and rostral ACC in the modulation of amygdala activation during extinction of cue conditioned fear in studies of human fear conditioning (Delgado et al., 2008; Milad et al., 2007; Phelps et al., 2004), studies examining the extinction of contextual fear have implicated a larger role for the dACC (Lang et al., 2009; Sehlmeyer et al., 201”
From Neural correlates of emotion acceptance<i>vs</i>worry or suppression in generalized anxiety disorder (2017) · cites this paper as Lang et al., 2009
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- Authors
- Lang, S., Kroll, A., Lipinski, S. J., Wessa, M., Ridder, S., Christmann, C., Schad, L. R., & Flor, H.
- Affiliations
- Heidelberg University (DE)
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2009-02
- Volume
- 29
- Issue
- 4
- Pages
- 823-832
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC2695154
- OpenAlex
- W1991878909
- Cited by
- 171
- References
- 72
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 8 · 2023: 3 · 2022: 7 · 2021: 8 · 2020: 10 · 2019: 11 · 2018: 18 · 2017: 12 · 2016: 15 · 2015: 11 · 2014: 16 · 2013: 16 · 2012: 10
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- 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 conditioning, extinction learning, hippocampus, amygdala, medial prefrontal cortex, anterior cingulate cortex, anxiety, contextual learning, hippocampal-amygdala interaction, neuronal connectivity
- MeSH terms
- Adult, Amygdala, Cerebral Cortex, Conditioning, Psychological, Cues, Electric Stimulation, Extinction, Psychological, Female, Galvanic Skin Response, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Photic Stimulation, Regression Analysis, Prefrontal Cortex, Young Adult
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