Highlights A single night of TMR benefits procedural memories up to 10 days later. Spindle density and SO-spindle coupling strength increase immediately upon cue onset. Time spent in N2 but not N3 predicts cueing benefit.

A growing body of evidence suggests that sleep can help to decouple the memory of emotional experiences from their associated affective charge. This process is thought to rely on the spontaneous reactivation of emotional memories during sleep, though it is still unclear which sleep stage is optimal for such reactivation. We examined this question by explicitly manipulating memory reactivation in both rapid-eye movement sleep (REM) and slow-wave sleep (SWS) using targeted memory reactivation (TMR) and testing the impact of this manipulation on habituation of subjective arousal responses across a night. Our results show that TMR during REM, but not SWS significantly decreased subjective arousal, and this effect is driven by the more negative stimuli. These results support one aspect of the sleep to forget, sleep to remember (SFSR) hypothesis which proposes that emotional memory reactivation during REM sleep underlies sleep-dependent habituation.

Memory reactivation during Non-Rapid Eye Movement (NREM) sleep is important for memory consolidation but it remains unclear exactly how such activity promotes the development of a stable memory representation. We used Targeted Memory Reactivation (TMR) in combination with longitudinal structural and functional MRI to track the evolution of a motor memory trace over 20 days. We show that repeated reactivation of motor memory during sleep leads to increased precuneus activation 24 h post-TMR. Interestingly, a decrease in precuneus activity over the next 10 days predicts longer-term cueing benefit. We also find both functional and structural changes in sensorimotor cortex in association with effects of TMR 20 days post-encoding. These findings demonstrate that TMR can engage precuneus in the short-term while also impacting on task-related structure and function over longer timescales.

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Targeted memory reactivation (TMR) is a technique in which sensory cues associated with memories during wake are used to trigger memory reactivation during subsequent sleep. The characteristics of such cued reactivation, and the optimal placement of TMR cues, remain to be determined. We built an EEG classification pipeline that discriminated reactivation of right- and left-handed movements and found that cues which fall on the up-going transition of the slow oscillation (SO) are more likely to elicit a classifiable reactivation. We also used a novel machine learning pipeline to predict the likelihood of eliciting a classifiable reactivation after each TMR cue using the presence of spindles and features of SOs. Finally, we found that reactivations occurred either immediately after the cue or one second later. These findings greatly extend our understanding of memory reactivation and pave the way for development of wearable technologies to efficiently enhance memory through cueing in sleep.

It is now well established that memories can reactivate during non-rapid eye movement sleep (non-REM), but the question of whether equivalent reactivation can be detected in rapid eye movement (REM) sleep is hotly debated. To examine this, we used a technique called targeted memory reactivation (TMR) in which sounds are paired with learned material in wake, and then re-presented in subsequent sleep, in this case REM, to trigger reactivation. We then used machine learning classifiers to identify reactivation of task related motor imagery from wake in REM sleep. Interestingly, the strength of measured reactivation positively predicted overnight performance improvement. These findings provide the first evidence for memory reactivation in human REM sleep after TMR that is directly related to brain activity during wakeful task performance.

Memories are reactivated during non-rapid eye movement (NREM) sleep, but the question of whether equivalent reactivation also occurs in rapid eye movement (REM) sleep is hotly debated. To examine this, we used a technique called targeted memory reactivation (TMR) in which sounds are paired with learned material in wake, and then re-presented in subsequent sleep to trigger reactivation. We then used machine learning classifiers to identify TMR-induced reactivation in REM. The reactivation we measured was temporally compressed by approximately five times during REM compared to wakeful performance of the task, and often occurred twice after a single TMR cue. Reactivation strength positively predicted overnight performance improvement and was only apparent in trials with high theta activity. These findings provide strong evidence for memory reactivation in human REM sleep after TMR as well as an initial characterisation of this reactivation.

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