Targeted memory reactivation during slow-wave sleep vs. sleep stage N2: no significant differences in a vocabulary task

Abstract

Sleep supports memory consolidation, and slow-wave sleep (SWS) in particular is assumed to benefit the consolidation of verbal learning material. Re-exposure to previously learned words during SWS with a technique known as targeted memory reactivation (TMR) consistently benefits memory. However, TMR has also been successfully applied during sleep stage N2, though a direct comparison between words selectively reactivated during SWS versus N2 is still missing. Here, we directly compared the effects of N2 TMR and SWS TMR on memory performance in a vocabulary learning task in a within-subject design. Thirty-four healthy young participants (21 in the main sample and 13 in an additional sample) learned 120 Dutch-German word pairs before sleep. Participants in the main sample slept for ∼8 h during the night, while participants in the additional sample slept ∼3 h. We reactivated the Dutch words selectively during N2 and SWS in one single night. Forty words were not cued. Participants in the main sample recalled the German translations of the Dutch words after sleep in the morning, while those in the additional sample did so at 2:00 a.m. As expected, we observed no differences in recall performance between words reactivated during N2 and SWS. However, we failed to find an overall memory benefit of reactivated over nonreactivated words. Detailed time-frequency analyses showed that words played during N2 elicited stronger characteristic oscillatory responses in several frequency bands, including spindle and theta frequencies, compared with SWS. These oscillatory responses did not vary with the memory strengths of individual words. Our results question the robustness and replicability of the TMR benefit on memory using our Dutch vocabulary learning task. We discuss potential boundary conditions for vocabulary reactivation paradigms and, most importantly, see the need for further replication studies, ideally including multiple laboratories and larger sample sizes.

Figure 1.

Experimental procedure and behavioral results. (A) Experimental procedure of the main study. After preparation, participants studied 120 Dutch–German word pairs in the evening. Afterward, participants went to bed and slept for 8 h. During stable N2 and SWS, we presented two separate lists of 40 Dutch words. Forty words were not presented. In the morning, participants were tested on the German translation of the Dutch words again. (B) Behavioral results of the main study. We did not detect any memory differences between selective reactivation during N2 sleep (N2 TMR) and slow-wave sleep (SWS TMR). In addition, we did not observe a general memory benefit for reactivated versus not reactivated words (control). In addition, retrieval performance is reported as a percentage of correctly retrieved German translations, with performance set to 100% before sleep. Values are mean ± SEM. (C) Behavioral results of the additional study (n = 13; identical design except 3 h of sleep instead of 8 h). Similar to our main study, we were not able to find any memory differences between selective reactivation during N2 sleep (N2 TMR) and during slow-wave sleep (SWS TMR). Analogously, we did not observe a general memory benefit for reactivated versus not reactivated words (control). Retrieval performance is reported as a percentage of correctly retrieved German translations, with performance set to 100% before sleep. Values are mean ± SEM.

Figure 2.

Averaged oscillatory responses to words presented during N2 and SWS in the time–frequency spectrum recorded at all frontal channels (F3, F4, Fz, F7, and F8) for memory-independent and memory-dependent processes. (A) Oscillatory power changes to all words presented during N2 and SWS show characteristic increases in the delta, theta, and alpha bands, followed by increases in the spindle and beta bands. (B) Oscillatory responses to all words presented in N2. (C) Oscillatory responses to all words presented during SWS. (D) Difference between the neural responses of all words in N2 and SWS. Responses in all different frequency bands were more pronounced after word presentations during N2 than in SWS (see the text for significant clusters). (E) For memory-dependent oscillatory processes, we did not observe any significant cluster when comparing oscillatory responses for all remembered words irrespective of the sleep stages when words were presented. (F) Similarly, there was no difference between the oscillatory responses of all remembered and nonremembered words during N2. (G) Also, there was no significant difference between the neural responses of all remembered and nonremembered words during SWS. (H) Consistently, we could not detect any significant increase or decrease between memory-dependent oscillatory processes after reactivation in N2 versus SWS.