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Medial prefrontal pathways for the contextual regulation of extinguished fear in humans
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Duke Univ, Ctr Cognit Neurosci, Durham, NC 27708 USA.;Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
Duke Univ, Ctr Cognit Neurosci, Durham, NC 27708 USA..
Duke Univ, Pratt Sch Engn, Durham, NC 27708 USA..
Duke Univ, Pratt Sch Engn, Durham, NC 27708 USA..
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2015 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 122, 262-271 p.Article in journal (Refereed) Published
Abstract [en]

The maintenance of anxiety disorders is thought to depend, in part, on deficits in extinction memory, possibly due to reduced contextual control of extinction that leads to fear renewal. Animal studies suggest that the neural circuitry responsible fear renewal includes the hippocampus, amygdala, and dorsomedial (dmPFC) and ventromedial (vmPFC) prefrontal cortex. However, the neural mechanisms of context-dependent fear renewal in humans remain poorly understood. We used functional magnetic resonance imaging (fMRI), combined with psychophysiology and immersive virtual reality, to elucidate how the hippocampus, amygdala, and dmPFC and vmPFC interact to drive the context-dependent renewal of extinguished fear. Healthy human participants encountered dynamic fear-relevant conditioned stimuli (CSs) while navigating through 3-D virtual reality environments in the MRI scanner. Conditioning and extinction were performed in two different virtual contexts. Twenty-four hours later, participants were exposed to the CSs without reinforcement while navigating through both contexts in the MRI scanner. Participants showed enhanced skin conductance responses (SCRs) to the previously-reinforced CS + in the acquisition context on Day 2, consistent with fear renewal, and sustained responses in the dmPFC. In contrast, participants showed low SCRs to the CSs in the extinction context on Day 2, consistent with extinction recall, and enhanced vmPFC activation to the non-reinforced CS -. Structural equation modeling revealed that the dmPFC fully mediated the effect of the hippocampus on right amygdala activity during fear renewal, whereas the vmPFC partially mediated the effect of the hippocampus on right amygdala activity during extinction recall. These results indicate dissociable contextual influences of the hippocampus on prefrontal pathways, which, in turn, determine the level of reactivation of fear associations.

Place, publisher, year, edition, pages
2015. Vol. 122, 262-271 p.
Keyword [en]
Fear conditioning, Amygdala, Hippocampus, Anterior cingulate cortex, Ventromedial prefrontal cortex, Extinction, Virtual reality, Functional magnetic resonance imaging
National Category
Psychology Neurology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-267179DOI: 10.1016/j.neuroimage.2015.07.051ISI: 000363125200026PubMedID: 26220745OAI: oai:DiVA.org:uu-267179DiVA: diva2:872764
Funder
NIH (National Institute of Health), R01 DA027802Swedish Research Council
Available from: 2015-11-20 Created: 2015-11-19 Last updated: 2017-12-01Bibliographically approved

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Åhs, Fredrik

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