Memory reactivations affect stability of declarative memories dependent on the brain state. During SWS, hippocampal replay stabilizes memories, while reactivations triggered during wakefulness destabilize memories. Previous human studies on neuronal reactivations during REM sleep mostly focused on procedural memories (Guerrien et al., 1989; Maquet et al., 2000), or did not specifically test for the stability of declarative memories after their reactivation during REM sleep (Rasch et al., 2007). The first manuscript has closed this research gap by investigating the effects of induced memory reactivations during REM sleep for memory stability.
In line with our hypothesis, cueing declarative memories during REM sleep did not benefit memory stability. This not only contradicts experimental findings of a beneficial role of REM sleep for memory, but also theoretical notions of a period of stabilization during REM sleep (Diekelmann & Born, 2010). In contrast, the wake-like electrophysiological and neurochemical character of REM sleep had given reason to expect a deteriorating influence of reactivations during REM sleep, but also these assumptions were not confirmed by the data, as cueing did not destabilize declarative memory either. This implies that hippocampal reactivations observed during REM sleep have no functional role for the stabilization of declarative memories. This conclusion finds further support in the fact that declarative memory stabilization had already been achieved after cueing during SWS in the study by Diekelmann et al. (2011). Possibly, reactivations only stabilize memories when SWS specific features are prevalent and thus, they have no stabilizing function when they occur during REM sleep. It could even be speculated that the replays observed in REM sleep are merely some kind of aftereffects of reactivations during SWS without any functional relevance. As data of several studies shows no impairment of declarative memory consolidation after lacking REM sleep (for an overview see McGrath & Cohen, 1978), it is also reasonable to assume that REM sleep generally has no
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functional role for declarative memory. There are recent reviews that either deny a major role of REM sleep for memory consolidation (Siegel, 2001) or at least question its necessity and state uncertainty as to possible memory related mechanisms (Tononi & Cirelli, 2014). However, the nature of REM sleep actually entails characteristics that could be beneficial for memory processes. For instance, literature offers evidence that theta activity is critically involved in the strengthening of new memory traces (Poe et al., 2000) and the induction of LTP (Maquet, 2001; Pavlides et al., 1988). Further, theta power in REM sleep has been shown to contribute to the organization of firing patterns in terms of rate and synchrony during sleep, which hints at a fundamental role in physiological memory processes during sleep (Grosmark, Mizuseki, Pastalkova, Diba, & Buzsáki, 2012). It should be noted that these studies were based on animal research and, although quantitatively meager, patterns in humans are not fully in line with results in animals (Caplan, Madsen, Raghavachari, & Kahana, 2014). However, besides theta, also the neurochemical milieu during REM sleep offers advantageous conditions. For instance, ACh levels are assumed to influence the facility of neuronal activation spreading. While during REM sleep high cholinergic tone in hippocampal areas suppresses output from this region, relatively lower ACh levels in the neocortex enable communication and spreading of activation within associated neocortical networks (Cai, Mednick, Harrison, Kanady, & Mednick, 2009; Hasselmo, 1999; Payne, 2011). This expanding reciprocal activation favors the establishment of connections between similar memory traces and the formation of new networks. The symbiosis of new information and remote networks enables reorganization and the formation of new associative elements, the basis for creative problem solving (Cai et al., 2009; Landmann et al., 2014). Accordingly, Payne (2011) suggests that induced reactivations during REM sleep support restructuring and recombination of memory contents within neocortex which promotes insight and creative solutions. One conclusion arising from this notion is that new memories benefit during REM sleep if they can be connected to existing networks during this spreading activation period. Thus, beneficial effects of REM sleep for memory might be observable following an inverted u-shaped function of connectability between newly learned material and existing networks: If associations are already over-learned or too strong to elicit further linkage (comparable to a ceiling effect) or if no schema exists in which the newly learned material can be integrated, memories cannot benefit from REM sleep. However, remotely associated items might benefit the support of REM sleep by finding even distant connections to networks in which they can be integrated. These assumptions find evidence in the results of two studies. One study demonstrated improved problem solving after sleep versus wake for difficult, but not easy problems. It was concluded that in the case of easy problems, characterized by many associative links between stimuli and target word, activation was not required to spread widely to reach associable targets and thus can happen with or without sleep. On the contrary, those items with few associative links to
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pre-existing networks need the support of sleep to spread widely enough to reach remotely associated links (Sio, Monaghan, & Ormerod, 2013). The second study showed a particularly enhanced priming effect for weakly associated word pairs compared to closely associated ones (Stickgold, Scott, Rittenhouse, & Hobson, 1999). Here, this difference only appeared after REM sleep periods, but not after NonREM sleep or wakefulness (Stickgold et al., 1999). It can thus be further concluded that particularly REM sleep enables widespread activation, which even allows remotely associated schemata to get connected. In short, reactivations during SWS might reflect the transmission of newly formed memory traces to neocortex while reactivations during REM sleep cause coupling and restructuring of transferred and remote memories (Payne, 2011).
Together, our data supports evidence attributing no functional role of REM sleep reactivations for memory stability. However, this does neither exclude other REM sleep features from contributing to memory formation nor a qualitatively different contribution of REM sleep reactivations to memory processing. Both possibilities should be further examined.