Amsterdam UMC, Vrije Universiteit Amsterdam, Department Anatomy & Neuroscience, Boelelaan 1081 HV Amsterdam, the Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Psychiatry, Oldenaller 1081 HJ Amsterdam, the Netherlands; Amsterdam Neuroscience, Mood Anxiety Psychosis Stress Sleep, Boelelaan 1081 HV Amsterdam, the Netherlands; University of Amsterdam, Department of Psychology, Brain & Cognition, Nieuwe Achtergracht 1018 WS Amsterdam, the Netherlands.
Amsterdam UMC, Vrije Universiteit Amsterdam, Department Anatomy & Neuroscience, Boelelaan 1081 HV Amsterdam, the Netherlands; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention, Boelelaan 1081 HV Amsterdam, the Netherlands.
Curr Biol. 2024 Aug 19;34(16):3735-3746.e5. doi: 10.1016/j.cub.2024.07.019. Epub 2024 Aug 7.
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.
创伤后应激障碍（PTSD）是一种以创伤性记忆为核心的精神障碍。治疗后睡眠可能提供了一个独特的时间窗口，可以通过巩固治疗性修改后的创伤性记忆来提高治疗效果。靶向记忆再激活（TMR）通过在睡眠期间呈现提示线索（例如与记忆相关的声音）来增强记忆巩固。在这里，我们在 EMDR 治疗后一次治疗会议后，在 PTSD 患者中应用 TMR 来增强治疗性记忆在睡眠中的巩固。PTSD 患者接受了慢波（SO）相位靶向 TMR，使用基于模型的闭环神经刺激（M-CLNS），将 EMDR 点击作为再激活线索（n=17），或假刺激（n=16）。通过高密度多导睡眠图评估 TMR 对睡眠的影响。通过对靶向创伤性记忆和整体 PTSD 症状水平的脚本驱动想象（SDI）的主观、自主和 fMRI 反应评估 TMR 对治疗结果的影响。与假刺激相比，TMR 导致 SO 和纺锤波动力学的刺激锁定增加，这与 TMR 组 PTSD 症状的降低呈正相关。鉴于 SO 和纺锤波在记忆巩固中的作用，这些发现表明 TMR 可能增强了 EMDR 治疗记忆的巩固。临床上，TMR 与假刺激相比，在 SDI 期间导致回避水平的降低更大。TMR 不会干扰睡眠或引发噩梦。总之，这些数据首次提供了 TMR 可能是 PTSD 的一种安全可行的未来治疗增强策略的原理证明。需要进行后续研究，实施多夜 TMR 或 REM 睡眠期间的 TMR，以进一步确定 TMR 对创伤性记忆的临床效果。
