Subregions in the ventromedial prefrontal cortex integrate threat and protective information to meta-represent safety

PLoS Biol. 2025 Jan 13;23(1):e3002986. doi: 10.1371/journal.pbio.3002986. eCollection 2025 Jan.

Abstract

Pivotal to self-preservation is the ability to identify when we are safe and when we are in danger. Previous studies have focused on safety estimations based on the features of external threats and do not consider how the brain integrates other key factors, including estimates about our ability to protect ourselves. Here, we examine the neural systems underlying the online dynamic encoding of safety. The current preregistered study used 2 novel tasks to test 4 facets of safety estimation: Safety Prediction, Meta-representation, Recognition, and Value Updating. We experimentally manipulated safety estimation changing both levels of external threats and self-protection. Data were collected in 2 independent samples (behavioral N = 100; MRI N = 30). We found consistent evidence of subjective changes in the sensitivity to safety conferred through protection. Neural responses in the ventromedial prefrontal cortex (vmPFC) tracked increases in safety during all safety estimation facets, with specific tuning to protection. Further, informational connectivity analyses revealed distinct hubs of safety coding in the posterior and anterior vmPFC for external threats and protection, respectively. These findings reveal a central role of the vmPFC for coding safety.

MeSH terms

  • Adult
  • Brain Mapping / methods
  • Fear / physiology
  • Female
  • Humans
  • Magnetic Resonance Imaging* / methods
  • Male
  • Prefrontal Cortex* / physiology
  • Safety*
  • Young Adult