Safety processing shifts from hippocampal to network engagement across adolescence

Adolescence is a critical period that requires balancing exploration of uncertain and novel environments while maintaining safety. This task requires sophisticated neural integration of threat and safety cues to guide behavior. Yet little work has been conducted on threat and safety processing outside of conditioning paradigms, which, while valuable, lack the complexity to identify how the adolescent brain supports distinguishing threat from safety when both are present and as task contingencies change. In the current study, we take an approach that expands on elements of differential conditioning as well as conditioned inhibition. We recorded brain responses to external threat and self-oriented protection cues to examine how the adolescent brain supports threat-safety discrimination using 7-Tesla functional magnetic resonance imaging (fMRI). Our findings reveal an adolescent transition in the neural mechanisms supporting accurate threat-safety discrimination, with younger adolescents (12-14 years) relying predominantly on the hippocampus and older adolescents (15-17 years) utilizing a more integrated circuit involving hippocampus and anterior ventromedial prefrontal cortex (vmPFC) connectivity. Our results clarify how competition between threat and safety cues is resolved within the visual cortex, demonstrating enhanced perceptual sensitivity to protection that is independent of threat. By examining the dynamic encoding of safety to different stimuli, the current study advances our understanding of adolescent neurodevelopment and provides valuable insights into threat-safety discrimination beyond conventional conditioning models.