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  The role of hippocampal spatial representations in contextualization and generalization of fear

de Voogd, L. D., Murray, Y. P. J., Barte, R. M., van der Heide, A., Fernández, G., Doeller, C. F., et al. (2019). The role of hippocampal spatial representations in contextualization and generalization of fear. NeuroImage, 116308. doi:10.1016/j.neuroimage.2019.116308.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-1B01-C Version Permalink: http://hdl.handle.net/21.11116/0000-0005-8066-7
Genre: Journal Article

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 Creators:
de Voogd, Lycia D.1, 2, Author
Murray, Yannick P. J.1, Author
Barte, Ramona M.1, Author
van der Heide, Anouk1, Author
Fernández, Guillén1, Author
Doeller, Christian F.3, 4, Author              
Hermans, Erno J.1, Author
Affiliations:
1Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands, ou_persistent22              
2Department of Psychology, New York University, NY, USA, ou_persistent22              
3Egil and Pauline Braathen and Fred Kavli Centre for Cortical Microcircuits, Kavli Institute, Norwegian University of Science and Technology, Trondheim, Norway, ou_persistent22              
4Department Psychology (Doeller), MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_2591710              

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Free keywords: Pavlovian fear conditioning; Contextual conditioning; Virtual reality; Hippocampus; Ventromedial prefrontal cortex (vmPFC); BOLD-fMRI
 Abstract: Using contextual information to predict aversive events is a critical ability that protects from generalizing fear responses to safe contexts. Animal models have demonstrated the importance of spatial context representations within the hippocampal formation in contextualization of fear learning. The ventromedial prefrontal cortex (vmPFC) is known to play an important role in safety learning, possibly also through the incorporation of context information. However, if contextual representations are related to context-dependent expression of fear memory in humans remains unclear. Twenty-one healthy participants underwent functional MRI combined with a cue-context conditioning paradigm within a self-navigated virtual reality environment. The environment included two buildings (Threat and Safe context), which had distinct features outside but were identical inside. Within each context, participants saw two cues (CS+, CS-). The CS+ was consistently (100% reinforcement rate) paired with an electric shock in the Threat context, but never in the Safe context. The CS- was never paired with a shock. We found robust differential skin conductance responses (SCRs; CS+ ​> ​CS-) in the Threat context, but also within the Safe context, indicating fear generalization. Within the Safe context, vmPFC responses to the CS+ were larger than those in the Threat context. We furthermore found environment-specific representations for the two contexts in the training paradigm (i.e., before conditioning took place) in the hippocampus to be related to fear expression and generalization. Namely, participants with a weak context representation (z-score < 1.65) showed stronger fear generalization compared to participants with a strong context representation (z-score > 1.65). Thus, a weak neural representation strength of spatial context may explain overgeneralization of memory to safe contexts. In addition, our findings demonstrate that context-dependent regulation of fear expression engages ventromedial prefrontal pathways suggesting this involves a similar mechanism that is known to be involved in retrieval of extinction memory.

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Language(s): eng - English
 Dates: 2019-10-182019-03-092019-10-222019-10-25
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.neuroimage.2019.116308
PMID: 31669410
Other: Epub ahead of print
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Project name : Stress Resilience and Network-Feedback Training / STRESNET
Grant ID : 682591
Funding program : Horizon 2020
Funding organization : European Commission (EC)

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Title: NeuroImage
Source Genre: Journal
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Publ. Info: Orlando, FL : Academic Press
Pages: - Volume / Issue: - Sequence Number: 116308 Start / End Page: - Identifier: ISSN: 1053-8119
CoNE: https://pure.mpg.de/cone/journals/resource/954922650166