Hippocampal activation during contextual fear inhibition related to resilience in the early aftermath of trauma

Behav Brain Res. 2021 Jun 25:408:113282. doi: 10.1016/j.bbr.2021.113282. Epub 2021 Apr 2.


Background: Impaired contextual fear inhibition is often associated with posttraumatic stress disorder (PTSD). Our previous work has demonstrated that more hippocampal activation during a response inhibition task after trauma exposure was related to greater resilience and fewer future PTSD symptoms. In the current study, we sought to extend our previous findings by employing a contextual fear conditioning and extinction paradigm to further determine the role of the hippocampus in resilience and PTSD in the early aftermath of trauma.

Methods: Participants (N = 28) were recruited in the Emergency Department shortly after experiencing a traumatic event. A contextual fear inhibition task was conducted in a 3 T MRI scanner approximately two months post-trauma. Measures of resilience (CD-RISC) at time of scan and PTSD symptoms three months post-trauma were collected. The associations between hippocampal activation during fear conditioning and during the effect of context during extinction, and post-trauma resilience and PTSD symptoms at three-months were assessed.

Results: During fear conditioning, activation of the bilateral hippocampal region of interest (ROI) correlated positively with resilience (r = 0.48, p = 0.01). During the effect of context during extinction, greater bilateral hippocampal activation correlated with lower PTSD symptoms three months post-trauma after controlling for baseline PTSD symptoms, age and gender (r=-0.59, p=0.009).

Conclusions: Greater hippocampal activation was related to post-trauma resilience and lower PTSD symptoms three months post-trauma. The current study supports and strengthens prior findings suggesting the importance of hippocampus-dependent context processing as a mechanism for resilience versus PTSD risk, which could be a potential mechanistic target for novel early interventions.

Keywords: Emergency department; Fear conditioning; Fear extinction; Functional magnetic resonance imaging (fMRI); Hippocampus; Inhibition; Longitudinal study; Posttraumatic stress disorder (PTSD); Predictive biomarkers; Prospective study; Resilience; Trauma.

Publication types

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

MeSH terms

  • Adult
  • Conditioning, Classical / physiology*
  • Fear / physiology*
  • Female
  • Functional Neuroimaging
  • Hippocampus / physiopathology*
  • Humans
  • Inhibition, Psychological*
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Psychological Trauma / physiopathology*
  • Resilience, Psychological*
  • Stress Disorders, Post-Traumatic / physiopathology*