# The ventromedial prefrontal cortex in response to threat omission is associated with subsequent explicit safety memory

## TL;DR

The brain's ventromedial prefrontal cortex helps remember safety by processing when threats are absent, aiding long-term memory of safe situations.

## Contribution

The study identifies specific brain regions involved in encoding safety memory through the absence of threat.

## Key findings

- The ventromedial prefrontal cortex is linked to memory of safe associations when threats are omitted.
- The left dorsolateral prefrontal cortex is active during general outcome processing.
- Prefrontal and sensory brain regions work together to sustain safety memory.

## Abstract

In order to memorize and discriminate threatening and safe stimuli, the processing of the actual absence of threat seems crucial. Here, we measured brain activity with fMRI in response to both threat conditioned stimuli and their outcomes by combining threat learning with a subsequent memory paradigm. Participants (N = 38) repeatedly saw a variety of faces, half of which (CS+) were associated with an aversive unconditioned stimulus (US) and half of which were not (CS-). When an association was later remembered, the hippocampus had been more active (than when forgotten). However, the ventromedial prefrontal cortex predicted subsequent memory specifically during safe associations (CS- and US omission responses) and the left dorsolateral prefrontal cortex during outcomes in general (US and US omissions). In exploratory analyses of the theoretically important US omission, we found extended involvement of the medial prefrontal cortex and an enhanced functional connectivity to visual and somatosensory cortices, suggesting a possible function in sustaining sensory information for an integration with semantic memory. Activity in visual and somatosensory cortices together with the inferior frontal gyrus also predicted memory performance one week after learning. The findings imply the importance of a close interplay between prefrontal and sensory areas during the processing of safe outcomes—or ‘nothing’—to establish declarative safety memory.