Targeted Memory Reactivation Enhances PTSD Treatment Effectiveness

Hein van Marle

Credit: Amsterdam University Medical Center

A recent study suggests Targeted Memory Reactivation (TMR) could be a promising strategy to enhance the effectiveness of PTSD treatments like eye movement desensitization and reprocessing (EMDR) by strengthening memory consolidation processes during sleep.¹

“Our goal is to unlock sleep as a new treatment window for PTSD,” said lead investigator Hein van Marle, from Amsterdam University Medical Center, in a statement.² “This is the first proof of concept for potentially enhancing daytime treatment effects during sleep.”

Exposure-based therapy, such as imaginary exposure or EMDR, may be a first-choice treatment for PTSD, but up to 50% of patients do not respond well to this treatment.¹ Previous studies have shown it is possible to manipulate memory reprocessing sleep to improve sleep consolidation.

In this new study, investigators sought to see if phase-targeted TMR in patients with PTSD could increase the effectiveness of standard PTSD treatment, using the strategies together. The study included 33 patients with PTSD, assigned to either TMR group (n = 17; mean age: 42.47 years) who received EMDR sessions in the evening and TMR when they slept or the sham group (n = 16; mean age: 41.25 years) who only received EMDR sessions. Investigators recorded the brain waves of patients in both groups during sleep.

During EDMR sessions, investigators played a standard clicking sound in the background. At night, investigators played the same standard clicking sound when they were sleeping, hoping to boost the storage of the EMDR treatment memory and reduce PTSD symptoms.

Brain waves showed TMR did not affect sleep efficiency and continuity. The sleep diary reports also showed TMR did not affect subjective sleep quality. The sleep diaries revealed patients who received TMR did not report more nightmares during the intervention night, nor did they remember hearing the auditory stimulation during sleep.

Investigators found patients who received the clicking sound during sleep demonstrated greater levels of brain wave activities linked to memory processing and consolidation compared to patients who did not receive clicking sounds during sleep.

The changes in brain wave activity among patients receiving TMR were associated with greater reductions in PTSD symptoms. Also, these patients were less likely to avoid their traumatic memory when they listened to an audio clip retelling the traumatic event.

Patients receiving TMR and EMDR reported less re-experiencing (P < .001) and avoidance (P = .002) from baseline to post-intervention. Patients also had less re-experiencing (P < .001) and avoidance (P = .025) from baseline to follow-up.

Investigators observed minimum (rs = 0.575; P = .020) and maximum (rs = 0.523; P = .038) ERP amplitudes correlated with reductions in PTSD severity, as measured by the CAPS-5 W severity score. This suggests the greater SO amplification—deeper trough and higher peak—links to a more significant reduction of PTSD severity. Moreover, increased frontal slow sigma (11 – 13.25) power was associated with reduced PTSD symptoms, as measured by the PCL-5 intrusion subscale (P = .027).

However, there were no significant associations between physiological measures and the RSDI measures or the number of EMDR clicks (P > .10). Though these correlations were not significant within the sham group, suggesting the observed associations were specific to the TMR intervention.

Despite these findings, investigators did not see differences in improved PTSD symptoms among patients who received TMR and patients who only received EMDR.

“During the night of TMR stimulation, we saw that presenting the EMDR clicks effectively enhanced the sleep physiology responsible for memory consolidation, with more enhancement leading to more significant reductions in symptoms,” Van Marle said.² “But the stimulation during our experiment wasn’t enough to produce differences in most clinical outcomes, partly because the EMDR session was already quite effective.”

A follow-up study is slated to begin in the fall. The team plans to provide TMR treatment to patients for 5 consecutive nights and would like to see if repeated TMR will have a greater effect in reducing PTSD symptoms.

“The sleep and memory field has been wary to apply TMR in PTSD patients,” Van Marle said. “We are really happy to see that TMR has no negative effects on these patients. This gives us more confidence in applying it more frequently in our future work.”

References

1. ^{van der Heijden et al., Targeted memory reactivation to augment treatment in post-traumatic stress disorder, Current Biology (2024), https://doi.org/10.1016/j.cub.2024.07.019}
2. ^{Processing Traumatic Memories During Sleep Leads to Changes In The Brain Associated With Improvement in PTSD Symptoms. EurekAlert! August 7, 2024. https://www.eurekalert.org/news-releases/1053338. Accessed August 7, 2024.}