Fear extinction learning modulates large-scale brain connectivity

Neuroimage. 2021 Sep;238:118261. doi: 10.1016/j.neuroimage.2021.118261. Epub 2021 Jun 11.


Exploring the neural circuits of the extinction of conditioned fear is critical to advance our understanding of fear- and anxiety-related disorders. The field has focused on examining the role of various regions of the medial prefrontal cortex, insular cortex, hippocampus, and amygdala in conditioned fear and its extinction. The contribution of this 'fear network' to the conscious awareness of fear has recently been questioned. And as such, there is a need to examine higher/multiple cortical systems that might contribute to the conscious feeling of fear and anxiety. Herein, we studied functional connectivity patterns across the entire brain to examine the contribution of multiple networks to the acquisition of fear extinction learning and its retrieval. We conducted trial-by-trial analyses on data from 137 healthy participants who underwent a two-day fear conditioning and extinction paradigm in a functional magnetic resonance imaging (fMRI) scanner. We found that functional connectivity across a broad range of brain regions, many of which are part of the default mode, frontoparietal, and ventral attention networks, increased from early to late extinction learning only to a conditioned cue. The increased connectivity during extinction learning predicted the magnitude of extinction memory tested 24 h later. Together, these findings provide evidence supporting recent studies implicating distributed brain regions in learning, consolidation and expression of fear extinction memory in the human brain.

Keywords: Brain activation; Fear conditioning; Learning and memory; Neuroimaging and plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Brain / diagnostic imaging*
  • Brain / physiology
  • Brain Mapping
  • Conditioning, Psychological / physiology
  • Extinction, Psychological / physiology*
  • Fear / physiology*
  • Female
  • Galvanic Skin Response / physiology
  • Humans
  • Learning / physiology*
  • Magnetic Resonance Imaging
  • Male
  • Nerve Net / diagnostic imaging*
  • Nerve Net / physiology
  • Neuronal Plasticity / physiology*