Targeted memory reactivation to augment treatment in post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a psychiatric disorder with traumatic memories at its core. Post-treatment sleep may offer a unique time window to increase therapeutic efficacy through consolidation of therapeutically modified traumatic memories. Targeted memory reactivation (TMR) enhances memory consolidation by presenting reminder cues (e.g., sounds associated with a memory) during sleep. Here, we applied TMR in PTSD patients to strengthen therapeutic memories during sleep after one treatment session with eye movement desensitization and reprocessing (EMDR). PTSD patients received either slow oscillation (SO) phase-targeted TMR, using modeling-based closed-loop neurostimulation (M-CLNS) with EMDR clicks as a reactivation cue (n = 17), or sham stimulation (n = 16). Effects of TMR on sleep were assessed through high-density polysomnography. Effects on treatment outcome were assessed through subjective, autonomic, and fMRI responses to script-driven imagery (SDI) of the targeted traumatic memory and overall PTSD symptom level. Compared to sham stimulation, TMR led to stimulus-locked increases in SO and spindle dynamics, which correlated positively with PTSD symptom reduction in the TMR group. Given the role of SOs and spindles in memory consolidation, these findings suggest that TMR may have strengthened the consolidation of the EMDR-treatment memory. Clinically, TMR vs. sham stimulation resulted in a larger reduction of avoidance level during SDI. TMR did not disturb sleep or trigger nightmares. Together, these data provide first proof of principle that TMR may be a safe and viable future treatment augmentation strategy for PTSD. The required follow-up studies may implement multi-night TMR or TMR during REM sleep to further establish the clinical effect of TMR for traumatic memories.