Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert

Background: Extinction of conditioned fear is thought to forma new safety memory that is expressed in the context in which the extinction learning took place. Rodent studies implicate the ventromedial prefrontal cortex (vmPFC) and hippocampus in extinction recall and its modulation by context, respectively. The aim of the present study is to investigate the mediating anatomy of extinction recall in healthy humans. Methods: We used event-related functional magnetic resonance imaging (fMRI) and a 2-day fear conditioning and extinction protocol with skin conductance response as the index of conditioned responses. Results: During extinction recall, we found significant activations in vmPFC and hippocampus in response to the extinguished versus an unextinguished stimulus. Activation in these brain regions was positively correlated with the magnitude of extinction memory. Functional connectivity analysis revealed significant positive correlation between vmPFC and hippocampal activation during extinction recall. Conclusions: These results support the involvement of the human hippocampus as well as vmPFC in the recall of extinction memory. Furthermore, this provides a paradigm for future investigations of fronto-temporal function during extinction recall in psychiatric disorders such as posttraurnatic stress disorder.