Persistence of Amygdala-Hippocampal Connectivity and Multi-Voxel Correlation Structures During Awake Rest After Fear Learning Predicts Long-Term Expression of Fear

Cereb Cortex. 2017 May 1;27(5):3028-3041. doi: 10.1093/cercor/bhw145.


After encoding, memories undergo a process of consolidation that determines long-term retention. For conditioned fear, animal models postulate that consolidation involves reactivations of neuronal assemblies supporting fear learning during postlearning "offline" periods. However, no human studies to date have investigated such processes, particularly in relation to long-term expression of fear. We tested 24 participants using functional MRI on 2 consecutive days in a fear conditioning paradigm involving 1 habituation block, 2 acquisition blocks, and 2 extinction blocks on day 1, and 2 re-extinction blocks on day 2. Conditioning blocks were preceded and followed by 4.5-min rest blocks. Strength of spontaneous recovery of fear on day 2 served as a measure of long-term expression of fear. Amygdala connectivity primarily with hippocampus increased progressively during postacquisition and postextinction rest on day 1. Intraregional multi-voxel correlation structures within amygdala and hippocampus sampled during a block of differential fear conditioning furthermore persisted after fear learning. Critically, both these main findings were stronger in participants who exhibited spontaneous recovery 24 h later. Our findings indicate that neural circuits activated during fear conditioning exhibit persistent postlearning activity that may be functionally relevant in promoting consolidation of the fear memory.

Keywords: amygdala; fear conditioning; hippocampus; memory consolidation; ventromedial prefrontal cortex.

MeSH terms

  • Adolescent
  • Adult
  • Afferent Pathways / physiology*
  • Amygdala / diagnostic imaging
  • Amygdala / physiology*
  • Conditioning, Psychological / physiology*
  • Electroshock
  • Fear / physiology*
  • Fear / psychology
  • Female
  • Galvanic Skin Response / physiology
  • Heart Rate / physiology
  • Hippocampus / diagnostic imaging
  • Hippocampus / physiology*
  • Humans
  • Imaging, Three-Dimensional
  • Magnetic Resonance Imaging
  • Male
  • Oxygen / blood
  • Photic Stimulation
  • Pupil / physiology
  • Respiration
  • Rest
  • Statistics as Topic
  • Wakefulness / physiology*
  • Young Adult


  • Oxygen