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Medial prefrontal pathways for the contextual regulation of extinguished fear in humans.

Publication ,  Journal Article
Åhs, F; Kragel, PA; Zielinski, DJ; Brady, R; LaBar, KS
Published in: NeuroImage
November 2015

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.

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Published In

NeuroImage

DOI

EISSN

1095-9572

ISSN

1053-8119

Publication Date

November 2015

Volume

122

Start / End Page

262 / 271

Related Subject Headings

  • User-Computer Interface
  • Psychophysiology
  • Prefrontal Cortex
  • Neurology & Neurosurgery
  • Neural Pathways
  • Mental Recall
  • Male
  • Magnetic Resonance Imaging
  • Humans
  • Hippocampus
 

Citation

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Åhs, F., Kragel, P. A., Zielinski, D. J., Brady, R., & LaBar, K. S. (2015). Medial prefrontal pathways for the contextual regulation of extinguished fear in humans. NeuroImage, 122, 262–271. https://doi.org/10.1016/j.neuroimage.2015.07.051
Åhs, Fredrik, Philip A. Kragel, David J. Zielinski, Rachael Brady, and Kevin S. LaBar. “Medial prefrontal pathways for the contextual regulation of extinguished fear in humans.NeuroImage 122 (November 2015): 262–71. https://doi.org/10.1016/j.neuroimage.2015.07.051.
Åhs F, Kragel PA, Zielinski DJ, Brady R, LaBar KS. Medial prefrontal pathways for the contextual regulation of extinguished fear in humans. NeuroImage. 2015 Nov;122:262–71.
Åhs, Fredrik, et al. “Medial prefrontal pathways for the contextual regulation of extinguished fear in humans.NeuroImage, vol. 122, Nov. 2015, pp. 262–71. Epmc, doi:10.1016/j.neuroimage.2015.07.051.
Åhs F, Kragel PA, Zielinski DJ, Brady R, LaBar KS. Medial prefrontal pathways for the contextual regulation of extinguished fear in humans. NeuroImage. 2015 Nov;122:262–271.
Journal cover image

Published In

NeuroImage

DOI

EISSN

1095-9572

ISSN

1053-8119

Publication Date

November 2015

Volume

122

Start / End Page

262 / 271

Related Subject Headings

  • User-Computer Interface
  • Psychophysiology
  • Prefrontal Cortex
  • Neurology & Neurosurgery
  • Neural Pathways
  • Mental Recall
  • Male
  • Magnetic Resonance Imaging
  • Humans
  • Hippocampus