The Role of the Medial Prefrontal Cortex in Spatial Margin of Safety Calculations

Naturalistic observations show that animals pre-empt danger by moving to locations that increase their success in avoiding future threats. To test this in humans, we created a spatial margin of nsafety (MOS) decision task that quantifies pre-emptive avoidance by measuring the distance subjects place themselves to safety when facing different threats whose attack locations vary in predictability. Behavioral results show that human participants place themselves closer to safe locations when facing threats that attack in spatial locations with more outliers. Using both univariate and multivariate pattern analysis (MVPA) on fMRI data collected during a 2-hour session on participants of both sexes, we demonstrate a dissociable role for the vmPFC in MOS-related decision-making. MVPA results revealed that the posterior vmPFC encoded for more unpredictable threats with univariate analyses showing a functional coupling with the amygdala and hippocampus. Conversely, the anterior vmPFC was more active for the more predictable attacks and showed coupling with the striatum. Our findings converge in showing that during pre-emptive danger, the anterior vmPFC may provide a safety signal, possibly via foreseeable outcomes, while the posterior vmPFC drives unpredictable danger signals. Significance Statement A common observation in nature is that under conditions of uncertain danger, animals will stay close to safety – a behavioral metric known as spatial margin of safety (MOS). We adapt this metric to examine risky and safety decisions to unpredictable attack distances. Using multivariate and univariate fMRI, we demonstrate a novel dissociation of vmPFC in decision-making: the posterior vmPFC encoded for the more unpredictable threat and showed functional coupling with the amygdala and hippocampus, while the anterior vmPFC was more active for more predictable attacks. Our findings suggest that when pre-empting danger, the anterior vmPFC may provide a safety signal associated with predictable outcomes, while the posterior vmPFC may drive uncertain danger signals.