Encoding-Retrieval Similarity Reveals Distinct Neural Reinstatement of Safety Memories Following Counterconditioning...

Posttraumatic stress disorder (PTSD) is characterized by deficits in the ability to retrieve extinction memories, which likely contribute to symptom relapse over time. Adapting a hybrid Pavlovian conditioning and episodic memory paradigm, we examined whether counterconditioning produces a more stable and persistent long-term neural memory trace of safety compared with standard extinction in the ventromedial prefrontal cortex (vmPFC)-a region associated with the learning and retrieval of safety.

Participants consisted of 32 individuals (27 female) who met diagnostic criteria for PTSD and 21 healthy (13 female) comparison participants. Participants completed a multiday Pavlovian conditioning and episodic memory paradigm with standard extinction/counterconditioning.

In healthy adults, we identified overlapping multivariate patterns of functional magnetic resonance imaging activity in the vmPFC associated with the formation and 24-hour retrieval of stimuli that underwent counterconditioning, but neural reinstatement diminished after ∼1 month. This pattern was reversed in PTSD, such that neural reinstatement of counterconditioning was not observed the day after safety learning but did emerge a month later. Interestingly, participants with PTSD showed reinstatement of standard extinction memories in the dorsal anterior cingulate cortex-a region associated with learning and retrieval of threat-both 24 hours and 1 month after safety learning.

These results provide the first evidence that counterconditioning may stabilize a long-term safety memory trace in PTSD. These effects seem to emerge over longer time scales, suggesting that counterconditioning could be an effective strategy for sustained treatment gains.