Susanne Diekelmann

The memory function of sleep

Sleep has been identified as a state that optimizes the consolidation of newly acquired information in memory, depending on the specific conditions of learning and the timing of sleep. Consolidation during sleep promotes both quantitative and qualitative changes of memory representations. Through specific patterns of neuromodulatory activity and electric field potential oscillations, slow-wave sleep (SWS) and rapid eye movement (REM) sleep support system consolidation and synaptic consolidation, respectively. During SWS, slow oscillations, spindles and ripples — at minimum cholinergic activity — coordinate the re-activation and redistribution of hippocampus-dependent memories to neocortical sites, whereas during REM sleep, local increases in plasticity-related immediate-early gene activity — at high cholinergic and theta activity — might favour the subsequent synaptic consolidation of memories in the cortex.

The whats and whens of sleep-dependent memory consolidation

Sleep benefits memory consolidation. The reviewed studies indicate that this consolidating effect is not revealed under all circumstances but is linked to specific psychological conditions. Specifically, we discuss to what extent memory consolidation during sleep depends on the type of learning materials, type of learning and retrieval test, different features of sleep and the subject population. Post-learning sleep enhances consolidation of declarative, procedural and emotional memories. The enhancement is greater for weakly than strongly encoded associations and more consistent for explicitly than implicitly encoded memories. Memories associated with expected reward gain preferentially access to sleep-dependent consolidation. For declarative memories, sleep benefits are more consistently revealed with recall than recognition procedures at retrieval testing. Slow wave sleep (SWS) particularly enhances declarative memories whereas rapid eye movement (REM) sleep preferentially supports procedural and emotional memory aspects. Declarative memory profits already from rather short sleep periods (1-2 h). Procedural memory profits seem more dose-dependent on the amount of sleep following the day after learning. Childrens sleep with high amounts of SWS distinctly enhances declarative memories whereas elderly and psychiatric patients with disturbed sleep show impaired sleep-associated consolidation often of declarative memories. Based on the constellation of psychological conditions identified we hypothesize that access to sleep-dependent consolidation requires memories to be encoded under control of prefrontal-hippocampal circuitry, with the same circuitry controlling subsequent consolidation during sleep.

Sleep Selectively Enhances Memory Expected to Be of Future Relevance

The brain encodes huge amounts of information, but only a small fraction is stored for a longer time. There is now compelling evidence that the long-term storage of memories preferentially occurs during sleep. However, the factors mediating the selectivity of sleep-associated memory consolidation are poorly understood. Here, we show that the mere expectancy that a memory will be used in a future test determines whether or not sleep significantly benefits consolidation of this memory. Human subjects learned declarative memories (word paired associates) before retention periods of sleep or wakefulness. Postlearning sleep compared with wakefulness produced a strong improvement at delayed retrieval only if the subjects had been informed about the retrieval test after the learning period. If they had not been informed, retrieval after retention sleep did not differ from that after the wake retention interval. Retention during the wake intervals was not affected by retrieval expectancy. Retrieval expectancy also enhanced sleep-associated consolidation of visuospatial (two-dimensional object location task) and procedural motor memories (finger sequence tapping). Subjects expecting the retrieval displayed a robust increase in slow oscillation activity and sleep spindle count during postlearning slow-wave sleep (SWS). Sleep-associated consolidation of declarative memory was strongly correlated to slow oscillation activity and spindle count, but only if the subjects expected the retrieval test. In conclusion, our work shows that sleep preferentially benefits consolidation of memories that are relevant for future behavior, presumably through a SWS-dependent reprocessing of these memories.

Labile or stable: opposing consequences for memory when reactivated during waking and sleep

Memory consolidation is a dynamic process. Reconsolidation theory assumes that reactivation during wakefulness transiently destabilizes memories, requiring them to reconsolidate in order to persist. Memory reactivation also occurs during slow-wave sleep (SWS) and is assumed to underlie the consolidating effect of sleep. Here, we tested whether the same principle of transient destabilization applies to memory reactivation during SWS. We reactivated memories in humans by presenting associated odor cues either during SWS or wakefulness. Reactivation was followed by an interference task to probe memory stability. As we expected, reactivation during waking destabilized memories. In contrast, reactivation during SWS immediately stabilized memories, thereby directly increasing their resistance to interference. Functional magnetic resonance imaging revealed that reactivation during SWS mainly activated hippocampal and posterior cortical regions, whereas reactivation during wakefulness primarily activated prefrontal cortical areas. Our results show that reactivation of memory serves distinct functions depending on the brain state of wakefulness or sleep.

Slow-wave sleep takes the leading role in memory reorganization

We recently proposed a comprehensive framework for sleep-dependent memory consolidation suggesting that, during slowwave sleep (SWS), memory representations are transferred from a temporary to a longterm store and thereby undergo reorganization in a process of system consolidation (The memory function of sleep. Nature Rev. Neurosci. 11, 114–126 (2010))1. Further, we suggested that this system consolidation process is complemented by the strengthening of synaptic connections — that is, synaptic consolidation — during the ensuing rapid eye movement (REM) sleep. Walker and Stickgold extend this framework by specifying cognitive features that are essential to the process of memory reorganization during sleep (Overnight alchemy: sleep-dependent memory evolution. Nature Rev. Neurosci. 19 Feb 2010 (doi:10.1038/nrn2762-c1))2. Four processes are proposed: an initial hippocampal binding of separate neocortical memory traces, followed by the unitization, assimilation and abstraction of more generalized representations at the neocortical level. This is an elegant cognitive concept that compellingly integrates some recent findings on the effects of sleep on problem-solving tasks. However, Walker and Stickgold’s proposal2 to link such processes of reorganization to REM sleep seems to be at some variance with the available experimental evidence. Forming part of a superordinate system consolidation process, the proposed ‘evolutionary’ stages of memory consolidation are more likely to take place during SWS, for three reasons. First, the reorganization of memory representations requires the reactivation of the representations. At the neuronal level, memory reactivation seems to occur most robustly during SWS3–5 and rarely during REM sleep. Of note, reports of dreams after awakenings from REM sleep in this context are often mistaken for indicators of the occurrence of memory reactivation during REM sleep. However, such reports are generated while the brain is ‘awake’ and do not necessarily provide an accurate picture of the processes that actually take place during REM sleep. Second, there is considerable evidence (summarized in REF. 1) that electrophysiological phenomena linked to SWS, such as sharp wave-ripples, spindles and slow oscillations, coordinately contribute to the transfer of memory information from the hippocampus to the neocortex, a process that is thought to underlie the proposed reorganization of memory representations6,7. Low acetylcholinergic tone, which occurs during SWS, is a further prerequisite for such transfer8,9. Third, a direct comparison of the effects of REM-rich and SWSrich sleep has provided solid behavioural evidence that the proposed process of ‘abstraction’ — that is, gaining insight into hidden rules — benefits from SWS rather than REM sleep10. All this does not exclude a contribution of REM sleep to the reorganization of memories beyond that of a synaptic strengthening of the reorganized (neocortical) representations. However, the ultimate contributions of REM sleep to memory consolidation have so far remained enigmatic11. Given the many proposals for the role of REM sleep in memory, it seems that the time is ripe to subject some of these proposals to systematic scrutiny.

Pharmacological REM sleep suppression paradoxically improves rather than impairs skill memory

Rapid eye movement (REM) sleep has been considered important for consolidation of memories, particularly of skills. Contrary to expectations, we found that REM sleep suppression by administration of selective serotonin or norepinephrine re-uptake inhibitors after training did not impair consolidation of skills or word-pairs in healthy men but rather enhanced gains in finger tapping accuracy together with sleep spindles. Our results indicate that REM sleep as a unitary phenomenon is not required for skill-memory consolidation.

Sleep in children improves memory performance on declarative but not procedural tasks

Sleep supports the consolidation of memory in adults. Childhood is a period hallmarked by huge demands of brain plasticity as well as great amounts of efficient sleep. Whether sleep supports memory consolidation in children as in adults is unclear. We compared effects of nocturnal sleep (versus daytime wakefulness) on consolidation of declarative (word-pair associates, two-dimensional [2D] object location), and procedural memories (finger sequence tapping) in 15 children (6-8 yr) and 15 adults. Beneficial effects of sleep on retention of declarative memories were comparable in children and adults. However, opposite to adults, children showed smaller improvement in finger-tapping skill across retention sleep than wakefulness, indicating that sleep-dependent procedural memory consolidation depends on developmental stage.

The role of REM sleep in the processing of emotional memories: Evidence from behavior and event-related potentials

Emotional memories are vividly remembered for the long-term. Rapid eye movement (REM) sleep has been repeatedly proposed to support the superior retention of emotional memories. However, its exact contribution and, specifically, whether its effect is mainly on the consolidation of the contents or the processing of the affective component of emotional memories is not clear. Here, we investigated the effects of sleep rich in slow wave sleep (SWS) or REM sleep on the consolidation of emotional pictures and the accompanying changes in affective tone, using event-related potentials (ERPs) together with subjective ratings of valence and arousal. Sixteen healthy, young men learned 50 negative and 50 neutral pictures before 3-h retention sleep intervals that were filled with either SWS-rich early or REM sleep-rich late nocturnal sleep. In accordance with our hypothesis, recognition was better for emotional pictures than neutral pictures after REM compared to SWS-rich sleep. This emotional enhancement after REM-rich sleep expressed itself in an increased late positive potential of the ERP over the frontal cortex 300-500 ms after stimulus onset for correctly classified old emotional pictures compared with new emotional and neutral pictures. Valence and arousal ratings of emotional pictures were not differentially affected by REM or SWS-rich sleep after learning. Our results corroborate that REM sleep contributes to the consolidation of emotional contents in memory, but suggest that the affective tone is preserved rather than reduced by the processing of emotional memories during REM sleep.

Offline consolidation of memory varies with time in slow wave sleep and can be accelerated by cuing memory reactivations

Memory representations are reactivated during slow-wave sleep (SWS) after learning, and these reactivations cause a beneficial effect of sleep for memory consolidation. Memory reactivations can also be externally triggered during sleep by associated cues which enhance the sleep-dependent memory consolidation process. Here, we compared in humans the influence of sleep periods (i) of 40min and (ii) of 90min without externally triggered reactivations and (iii) of externally triggered reactivations by an associated odor cue during a 40-min sleep period on the consolidation of previously learned hippocampus-dependent visuo-spatial memories. We show that external reactivation by an odor cue during the 40-min sleep period enhanced memory stability to the same extent as 90min of sleep without odor reactivation. In contrast, 40min of sleep without external reactivations were not sufficient to benefit memory. In the 90-min sleep condition, memory enhancements were associated with time spent in SWS and were independent of the presence or absence of REM sleep. These results suggest that the efficacy of hippocampus-dependent memory consolidation depends on the duration of sleep and particularly SWS. External reactivation cues can accelerate the consolidation process even during shorter sleep episodes.

Napping to renew learning capacity: enhanced encoding after stimulation of sleep slow oscillations.

As well as consolidating memory, sleep has been proposed to serve a second important function for memory, i.e. to free capacities for the learning of new information during succeeding wakefulness. The slow wave activity (SWA) that is a hallmark of slow wave sleep could be involved in both functions. Here, we aimed to demonstrate a causative role for SWA in enhancing the capacity for encoding of information during subsequent wakefulness, using transcranial slow oscillation stimulation (tSOS) oscillating at 0.75 Hz to induce SWA in healthy humans during an afternoon nap. Encoding following the nap was tested for hippocampus‐dependent declarative materials (pictures, word pairs, and word lists) and procedural skills (finger sequence tapping). As compared with a sham stimulation control condition, tSOS during the nap enhanced SWA and significantly improved subsequent encoding on all three declarative tasks (picture recognition, cued recall of word pairs, and free recall of word lists), whereas procedural finger sequence tapping skill was not affected. Our results indicate that sleep SWA enhances the capacity for encoding of declarative materials, possibly by down‐scaling hippocampal synaptic networks that were potentiated towards saturation during the preceding period of wakefulness.