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

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.

To remember or not to remember: Neural oscillations and ERPs as predictors of intentional associative fear learning.

It is widely accepted that impaired safety learning to a safe stimulus is a pathological feature of anxiety disorders. Safety learning refers to learning that a stimulus is associated with the absence of threat. Cognitive mechanisms that underlie successful threat and safety learning are, however, poorly understood. This study aimed to identify various physiological markers, including neural oscillations and event-related potentials (ERPs) that predict successful threat and safety learning. Therefore, to detect potential differences in these markers, we measured EEG in a fear learning framework combined with a subsequent memory paradigm. Thirty-seven participants were asked to memorize a series of associations between faces and an aversive unconditioned stimulus (US) or its omission. We found a decrease of power in the alpha band in occipital brain regions during learning for both threatening (conditioned stimuli, CS+) and safe faces (control stimuli, CS-) that were subsequently remembered to be associated with a US or not. No effects in theta band were found. In regard to ERPs, a late positive potential (LPP) and a P300 component were larger for remembered than for forgotten CS-US associations. The P300 was also enhanced to remembered US and US omissions, thus replicating previous findings. These results point to the importance of cognitive resource allocation as an underlying mechanism of fear learning and electrophysiological measurements as potential biomarkers for successful threat and safety learning.

Subsequent memory effects on event-related potentials in associative fear learning.

Studies of human fear learning suggest that a reliable discrimination between safe and threatening stimuli is important for survival and mental health. In the current study, we applied the subsequent memory paradigm in order to identify neurophysiological correlates of successful threat and safety learning. We recorded event-related potentials, while participants incidentally learned associations between multiple neutral faces and an aversive outcome [unconditioned stimulus (US)/conditioned stimulus (CS)+] or no outcome (noUS/CS-). We found that an enhanced late positive potential (LPP) to both CS+ and CS- during learning predicted subsequent memory. A quadratic relationship between LPP and confidence in memory indicates a possible role in both correct and false fear memory. Importantly, the P300 to the omission of the US (following CS-) was enhanced for remembered CS-, while there was a positive correlation between P300 amplitude to both US occurrence and omission and individual memory performance. A following re-exposure phase indicated that memory was indeed related to subjective fear of the CS+/CS-. These results highlight the importance of cognitive resource allocation to both threat and safety for the acquisition of fear and suggest a potential role of the P300 to US omission as an electrophysiological marker of successful safety learning.