Encoding-Retrieval Similarity Reveals Distinct Neural Reinstatement of Safety Memories Following Counterconditioning in Posttraumatic Stress Disorder.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.