Memory for semantically related and unrelated declarative information: the benefit of sleep, the cost of wake

Numerous studies have examined sleep's influence on a range of hippocampus-dependent declarative memory tasks, from text learning to spatial navigation. In this study, we examined the impact of sleep, wake, and time-of-day influences on the processing of declarative information with strong semantic links (semantically related word pairs) and information requiring the formation of novel associations (unrelated word pairs). Participants encoded a set of related or unrelated word pairs at either 9 am or 9 pm, and were then tested after an interval of 30 min, 12 hr, or 24 hr. The time of day at which subjects were trained had no effect on training performance or initial memory of either word pair type. At 12 hr retest, memory overall was superior following a night of sleep compared to a day of wakefulness. However, this performance difference was a result of a pronounced deterioration in memory for unrelated word pairs across wake; there was no sleep-wake difference for related word pairs. At 24 hr retest, with all subjects having received both a full night of sleep and a full day of wakefulness, we found that memory was superior when sleep occurred shortly after learning rather than following a full day of wakefulness. Lastly, we present evidence that the rate of deterioration across wakefulness was significantly diminished when a night of sleep preceded the wake period compared to when no sleep preceded wake, suggesting that sleep served to stabilize the memories against the deleterious effects of subsequent wakefulness. Overall, our results demonstrate that 1) the impact of 12 hr of waking interference on memory retention is strongly determined by word-pair type, 2) sleep is most beneficial to memory 24 hr later if it occurs shortly after learning, and 3) sleep does in fact stabilize declarative memories, diminishing the negative impact of subsequent wakefulness.     

Effects of daytime food intake on memory consolidation during sleep or sleep deprivation

Sleep enhances memory consolidation. Bearing in mind that food intake produces many metabolic signals that can influence memory processing in humans (e.g., insulin), the present study addressed the question as to whether the enhancing effect of sleep on memory consolidation is affected by the amount of energy consumed during the preceding daytime. Compared to sleep, nocturnal wakefulness has been shown to impair memory consolidation in humans. Thus, a second question was to examine whether the impaired memory consolidation associated with sleep deprivation (SD) could be compensated by increased daytime energy consumption. To these aims, 14 healthy normal-weight men learned a finger tapping sequence (procedural memory) and a list of semantically associated word pairs (declarative memory). After the learning period, standardized meals were administered, equaling either ～50% or ～150% of the estimated daily energy expenditure. In the morning, after sleep or wakefulness, memory consolidation was tested. Plasma glucose was measured both before learning and retrieval. Polysomnographic sleep recordings were performed by electroencephalography (EEG). Independent of energy intake, subjects recalled significantly more word pairs after sleep than they did after SD. When subjects stayed awake and received an energy oversupply, the number of correctly recalled finger sequences was equal to those seen after sleep. Plasma glucose did not differ among conditions, and sleep time in the sleep conditions was not influenced by the energy intake interventions. These data indicate that the daytime energy intake level affects neither sleep's capacity to boost the consolidation of declarative and procedural memories, nor sleep's quality. However, high energy intake was followed by an improved procedural but not declarative memory consolidation under conditions of SD. This suggests that the formation of procedural memory is not only triggered by sleep but is also sensitive to the fluctuations in the energy state of the body.     

Sleep improves memory: the effect of sleep on long term memory in early adolescence

Sleep plays an important role in the consolidation of memory. This has been most clearly shown in adults for procedural memory (i.e. skills and procedures) and declarative memory (e.g. recall of facts). The effects of sleep and memory are relatively unstudied in adolescents. Declarative memory is important in school performance and consequent social functioning in adolescents. This is the first study to specifically examine the effects of normal sleep on auditory declarative memory in an early adolescent sample. Given that the majority of adolescents do not obtain the recommended amount of sleep, it is critical to study the cognitive effects of normal sleep. Forty male and female normal, healthy adolescents between the ages of ten and fourteen years old were randomly assigned to sleep and no sleep conditions. Subjects were trained on a paired-associate declarative memory task and a control working memory task at 9am, and tested at night (12 hours later) without sleep. The same number of subjects was trained at 9pm and tested 9am following sleep. An increase of 20.6% in declarative memory, as measured by the number correct in a paired-associate test, following sleep was observed compared to the group which was tested at the same time interval without sleep (p<0.03). The performance on the control working memory task that involved encoding and memoranda manipulation was not affected by time of day or relationship to sleep. Declarative memory is significantly improved by sleep in a sample of normal adolescents.     

Memory consolidation in sleep; dream or reality

We discuss several lines of evidence refuting the hypothesis that procedural or declarative memories are processed/consolidated in sleep. One of the strongest arguments against a role for sleep in declarative memory involves the demonstration that the marked suppression or elimination of REM sleep in subjects on antidepressant drugs or with brainstem lesions produces no detrimental effects on cognition. Procedural memory, like declarative memory, undergoes a slow, time-dependent period of consolidation. A process has recently been described wherein performance on some procedural tasks improves with the mere passage of time and has been termed "enhancement." Some studies, but not others, have reported that the consolidation/enhancement of perceptual and motor skills is dependent on sleep. We suggest that consolidation or enhancement, initiated in waking with task acquisition, could in some instances extend to sleep, but sleep would serve no unique role in these processes. In sum, there is no compelling evidence to support a relationship between sleep and memory consolidation.     

Sequence Skill Acquisition and Off-Line Learning in Normal Aging

It is well known that certain cognitive abilities decline with age. The ability to form certain new declarative memories, particularly memories for facts and events, has been widely shown to decline with advancing age. In contrast, the effects of aging on the ability to form new procedural memories such as skills are less well known, though it appears that older adults are able to acquire some new procedural skills over practice. The current study examines the effects of normal aging on procedural memory more closely by comparing the effects of aging on the encoding or acquisition stage of procedural learning versus its effects on the consolidation, or between-session stage of procedural learning. Twelve older and 14 young participants completed a sequence-learning task (the Serial Reaction Time Task) over a practice session and at a re-test session 24 hours later. Older participants actually demonstrated more sequence skill during acquisition than the young. However, older participants failed to show skill improvement at re-test as the young participants did. Age thus appears to have a differential effect upon procedural learning stages such that older adults'' skill acquisition remains relatively intact, in some cases even superior, compared to that of young adults, while their skill consolidation may be poorer than that of young adults. Although the effect of normal aging on procedural consolidation remains unclear, aging may actually enhance skill acquisition on some procedural tasks.     

Interfering with theories of sleep and memory: sleep, declarative memory, and associative interference

Mounting behavioral evidence in humans supports the claim that sleep leads to improvements in recently acquired, nondeclarative memories. Examples include motor-sequence learning; visual-discrimination learning; and perceptual learning of a synthetic language. In contrast, there are limited human data supporting a benefit of sleep for declarative (hippocampus-mediated) memory in humans (for review, see). This is particularly surprising given that animal models (e.g.,) and neuroimaging studies (e.g.,) predict that sleep facilitates hippocampus-based memory consolidation. We hypothesized that we could unmask the benefits of sleep by challenging the declarative memory system with competing information (interference). This is the first study to demonstrate that sleep protects declarative memories from subsequent associative interference, and it has important implications for understanding the neurobiology of memory consolidation.     

Skill Memory Escaping from Distraction by Sleep��Evidence from Dual-Task Performance

Background

Sleep facilitates off-line consolidation of memories, as shown for learning of motor skills in the absence of concomitant distractors. We often perform complex tasks focusing our attention mostly on one single part of them. However, we are equally able to skillfully perform other concurrent tasks. One may even improve performance on disregarded parts of complex tasks, which were learned implicitly. In the present study we investigated the role of sleep in the off-line consolidation of procedural skills when attention is diverted from the procedural task because of interference from a concurrent task.

Methodology/Principal Findings

We used a dual-task paradigm containing (i) procedural serial reaction time task (SRTT), which was labeled as subordinate and unimportant and (ii) declarative word-pair association task (WPAT), performed concomitantly. The WPAT served as a masked distractor to SRTT and was strongly reinforced by the instructions. One experimental and three control groups were tested. The experimental group was re-tested after two nights of sleep (sleep group, SG). The first control group had sleep deprivation on the first post-learning night (nighttime-awake group, NA), the second control group was tested in the morning and then re-tested after 12-hours (daytime-awake group, DA); the third one had the same assignments as DA but with a subsequent, instead of a concomitant, WPAT (daytime-awake-subsequent-WPAT group, DAs). We found SRTT performance gains in SG but not in NA and DA groups. Furthermore, SG reached similar learning gains in SRTT as the DAs group, which gained in SRTT performance because of post-training interference from the declarative task.

Conclusions/Significance

The results demonstrate that sleep allows off-line consolidation, which is resistant to deteriorating effects of a reinforced distractor on the implicit procedural learning and allowing for gains which are consistent with those produced when inhibited declarative memories of SRTT do not compete with procedural ones.     

Intact Acquisition and Short-Term Retention of Non-Motor Procedural Learning in Parkinson’s Disease

Procedural learning is a form of memory where people implicitly acquire a skill through repeated practice. People with Parkinson’s disease (PD) have been found to acquire motor adaptation, a form of motor procedural learning, similarly to healthy older adults but they have deficits in long-term retention. A similar pattern of normal learning on initial exposure with a deficit in retention seen on subsequent days has also been seen in mirror-reading, a form of non-motor procedural learning. It is a well-studied fact that disrupting sleep will impair the consolidation of procedural memories. Given the prevalence of sleep disturbances in PD, the lack of retention on following days seen in these studies could simply be a side effect of this well-known symptom of PD. Because of this, we wondered whether people with PD would present with deficits in the short-term retention of a non-motor procedural learning task, when the test of retention was done the same day as the initial exposure. The aim of the present study was then to investigate acquisition and retention in the immediate short term of cognitive procedural learning using the mirror-reading task in people with PD. This task involved two conditions: one where triads of mirror-inverted words were always new that allowed assessing the learning of mirror-reading skill and another one where some of the triads were presented repeatedly during the experiment that allowed assessing the word-specific learning. People with PD both ON and OFF their normal medication were compared to healthy older adults and young adults. Participants were re-tested 50 minutes break after initial exposure to probe for short-term retention. The results of this study show that all groups of participants acquired and retained the two skills (mirror-reading and word-specific) similarly. These results suggest that neither healthy ageing nor the degeneration within the basal ganglia that occurs in PD does affect the mechanisms that underpin the acquisition of these new non-motor procedural learning skills and their short-term memories.     

The Significance of Sigma Neurofeedback Training on Sleep Spindles and Aspects of Declarative Memory

The functional significance of sleep spindles for overnight memory consolidation and general learning aptitude as well as the effect of four 10-minute sessions of spindle frequency (11.6–16 Hz, sigma) neurofeedback-training on subsequent sleep spindle activity and overnight performance change was investigated. Before sleep, subjects were trained on a paired-associate word list task after having received either neurofeedback training (NFT) or pseudofeedback training (PFT).Although NFT had no significant impact on subsequent spindle activity and behavioral outcomes, there was a trend for enhanced sigma band-power during NREM (stage 2 to 4) sleep after NFT as compared to PFT. Furthermore, a significant positive correlation between spindle activity during slow wave sleep (in the first night half) and overall memory performance was revealed. The results support the view that the considerable inter-individual variance in sleep spindle activity can at least be partly explained by differences in the ability to acquire new declarative information.We conclude that the short NFT before sleep was not sufficient to efficiently enhance phasic spindle activity and/or to influence memory processing. NFT was, however, successful in increasing sigma power, presumably because sigma NFT effects become more easily evident in actually trained frequency bands than in associated phasic spindle activity.The authors contributed equally to manuscipt     

After Being Challenged by a Video Game Problem,Sleep Increases the Chance to Solve It

In the past years many studies have demonstrated the role of sleep on memory consolidation. It is known that sleeping after learning a declarative or non-declarative task, is better than remaining awake. Furthermore, there are reports of a possible role for dreams in consolidation of declarative memories. Other studies have reported the effect of naps on memory consolidation. With similar protocols, another set of studies indicated that sleep has a role in creativity and problem-solving. Here we hypothesised that sleep can increase the likelihood of solving problems. After struggling to solve a video game problem, subjects who took a nap (n = 14) were almost twice as likely to solve it when compared to the wake control group (n = 15). It is interesting to note that, in the nap group 9 out 14 subjects engaged in slow-wave sleep (SWS) and all solved the problem. Surprisingly, we did not find a significant involvement of Rapid Eye Movement (REM) sleep in this task. Slow-wave sleep is believed to be crucial for the transfer of memory-related information to the neocortex and implement intentions. Sleep can benefit problem-solving through the generalisation of newly encoded information and abstraction of the gist. In conclusion, our results indicate that sleep, even a nap, can potentiate the solution of problems that involve logical reasoning. Thus, sleep''s function seems to go beyond memory consolidation to include managing of everyday-life events.     

Sleep loss produces false memories

People sometimes claim with high confidence to remember events that in fact never happened, typically due to strong semantic associations with actually encoded events. Sleep is known to provide optimal neurobiological conditions for consolidation of memories for long-term storage, whereas sleep deprivation acutely impairs retrieval of stored memories. Here, focusing on the role of sleep-related memory processes, we tested whether false memories can be created (a) as enduring memory representations due to a consolidation-associated reorganization of new memory representations during post-learning sleep and/or (b) as an acute retrieval-related phenomenon induced by sleep deprivation at memory testing. According to the Deese, Roediger, McDermott (DRM) false memory paradigm, subjects learned lists of semantically associated words (e.g., "night", "dark", "coal",...), lacking the strongest common associate or theme word (here: "black"). Subjects either slept or stayed awake immediately after learning, and they were either sleep deprived or not at recognition testing 9, 33, or 44 hours after learning. Sleep deprivation at retrieval, but not sleep following learning, critically enhanced false memories of theme words. This effect was abolished by caffeine administration prior to retrieval, indicating that adenosinergic mechanisms can contribute to the generation of false memories associated with sleep loss.     

Does Sleep Really Influence Face Recognition Memory?

Mounting evidence implicates sleep in the consolidation of various kinds of memories. We investigated the effect of sleep on memory for face identity, a declarative form of memory that is indispensable for nearly all social interaction. In the acquisition phase, observers viewed faces that they were required to remember over a variable retention period (0–36 hours). In the test phase, observers viewed intermixed old and new faces and judged seeing each before. Participants were classified according to acquisition and test times into seven groups. Memory strength (d′) and response bias (c) were evaluated. Substantial time spent awake (12 hours or more) during the retention period impaired face recognition memory evaluated at test, whereas sleep per se during the retention period did little to enhance the memory. Wakefulness during retention also led to a tightening of the decision criterion. Our findings suggest that sleep passively and transiently shelters face recognition memory from waking interference (exposure) but does not actively aid in its long-term consolidation.     

Susceptibility to Declarative Memory Interference is Pronounced in Primary Insomnia

Sleep has been shown to stabilize memory traces and to protect against competing interference in both the procedural and declarative memory domain. Here, we focused on an interference learning paradigm by testing patients with primary insomnia (N = 27) and healthy control subjects (N = 21). In two separate experimental nights with full polysomnography it was revealed that after morning interference procedural memory performance (using a finger tapping task) was not impaired in insomnia patients while declarative memory (word pair association) was decreased following interference. More specifically, we demonstrate robust associations of central sleep spindles (in N3) with motor memory susceptibility to interference as well as (cortically more widespread) fast spindle associations with declarative memory susceptibility. In general the results suggest that insufficient sleep quality does not necessarily show up in worse overnight consolidation in insomnia but may only become evident (in the declarative memory domain) when interference is imposed.     

Sleep-Related Declarative Memory Consolidation and Verbal Replay during Sleep Talking in Patients with REM Sleep Behavior Disorder

Objective

To determine if sleep talkers with REM sleep behavior disorder (RBD) would utter during REM sleep sentences learned before sleep, and to evaluate their verbal memory consolidation during sleep.

Methods

Eighteen patients with RBD and 10 controls performed two verbal memory tasks (16 words from the Free and Cued Selective Reminding Test and a 220-263 word long modified Story Recall Test) in the evening, followed by nocturnal video-polysomnography and morning recall (night-time consolidation). In 9 patients with RBD, daytime consolidation (morning learning/recall, evening recall) was also evaluated with the modified Story Recall Test in a cross-over order. Two RBD patients with dementia were studied separately. Sleep talking was recorded using video-polysomnography, and the utterances were compared to the studied texts by two external judges.

Results

Sleep-related verbal memory consolidation was maintained in patients with RBD (+24±36% words) as in controls (+9±18%, p=0.3). The two demented patients with RBD also exhibited excellent nighttime consolidation. The post-sleep performance was unrelated to the sleep measures (including continuity, stages, fragmentation and apnea-hypopnea index). Daytime consolidation (-9±19%) was worse than night-time consolidation (+29±45%, p=0.03) in the subgroup of 9 patients with RBD. Eleven patients with RBD spoke during REM sleep and pronounced a median of 20 words, which represented 0.0003% of sleep with spoken language. A single patient uttered a sentence that was judged to be semantically (but not literally) related to the text learned before sleep.

Conclusion

Verbal declarative memory normally consolidates during sleep in patients with RBD. The incorporation of learned material within REM sleep-associated sleep talking in one patient (unbeknownst to himself) at the semantic level suggests a replay at a highly cognitive creative level.     

Sleep supports selective retention of associative memories based on relevance for future utilization

An outstanding question is whether memory consolidation occurs passively or involves active processes that selectively stabilize memories based on future utility. Here, we differentially modulated the expected future relevance of two sets of picture-location associations after learning. Participants first studied two sets of picture-location associations. After a baseline memory test, they were instructed that only one set of associations would be retested after a 14-hour delay. For half of the participants, this test-retest delay contained a night of sleep; for the other half the delay included a normal working day. At retest, participants were re-instructed and against their expectations tested on both sets of associations. Our results show that post-learning instruction about subsequent relevance selectively improves memory retention for specific associative memories. This effect was sleep-dependent; it was present only in the group of subjects for which the test-retest delay contained sleep. Moreover, time spent asleep for participants in this sleep group correlated with retention of relevant but not irrelevant associations; participants who slept longer forgot fewer associations from the relevant category. In contrast, participants that did not sleep forgot more relevant than irrelevant associations across the test-retest delay. In summary, our results indicate that it is possible to modulate the retention of selected memories after learning with simple verbal instructions on their future relevance. The finding that this effect depends on sleep demonstrates this state's active role in memory consolidation and may have utility for educational settings.     

Reduced susceptibility to interference in the consolidation of motor memory before adolescence

Are children superior to adults in consolidating procedural memory? This notion has been tied to "critical," early life periods of increased brain plasticity. Here, using a motor sequence learning task, we show, in experiment 1, that a) the rate of learning during a training session, b) the gains accrued, without additional practice, within a 24 hours post-training interval (delayed consolidation gains), and c) the long-term retention of these gains, were as effective in 9, 12 and 17-year-olds and comparable to those reported for adults. However, a follow-up experiment showed that the establishment of a memory trace for the trained sequence of movements was significantly more susceptible to interference by a subsequent motor learning experience (practicing a reversed movement sequence) in the 17-year-olds compared to the 9 and 12-year-olds. Unlike the 17-year-olds, the younger age-groups showed significant delayed gains even after interference training. Altogether, our results indicate the existence of an effective consolidation phase in motor learning both before and after adolescence, with no childhood advantage in the learning or retention of a motor skill. However, the ability to co-consolidate different, successive motor experiences, demonstrated in both the 9 and 12-year-olds, diminishes after puberty, suggesting that a more selective memory consolidation process takes over from the childhood one. Only the adult consolidation process is gated by a recency effect, and in situations of multiple, clashing, experiences occurring within a short time-interval, adults may less effectively establish in memory experiences superseded by newer ones.     

Delayed Onset of a Daytime Nap Facilitates Retention of Declarative Memory

Background

Learning followed by a period of sleep, even as little as a nap, promotes memory consolidation. It is now generally recognized that sleep facilitates the stabilization of information acquired prior to sleep. However, the temporal nature of the effect of sleep on retention of declarative memory is yet to be understood. We examined the impact of a delayed nap onset on the recognition of neutral pictorial stimuli with an added spatial component.

Methodology/Principal Findings

Participants completed an initial study session involving 150 neutral pictures of people, places, and objects. Immediately following the picture presentation, participants were asked to make recognition judgments on a subset of “old”, previously seen, pictures versus intermixed “new” pictures. Participants were then divided into one of four groups who either took a 90-minute nap immediately, 2 hours, or 4 hours after learning, or remained awake for the duration of the experiment. 6 hours after initial learning, participants were again tested on the remaining “old” pictures, with “new” pictures intermixed.

Conclusions/Significance

Interestingly, we found a stabilizing benefit of sleep on the memory trace reflected as a significant negative correlation between the average time elapsed before napping and decline in performance from test to retest (p = .001). We found a significant interaction between the groups and their performance from test to retest (p = .010), with the 4-hour delay group performing significantly better than both those who slept immediately and those who remained awake (p = .044, p = .010, respectively). Analysis of sleep data revealed a significant positive correlation between amount of slow wave sleep (SWS) achieved and length of the delay before sleep onset (p = .048). The findings add to the understanding of memory processing in humans, suggesting that factors such as waking processing and homeostatic increases in need for sleep over time modulate the importance of sleep to consolidation of neutral declarative memories.     

Does Recall after Sleep-Dependent Memory Consolidation Reinstate Sensitivity to Retroactive Interference?

Previous studies have shown that newly encoded memories are more resistant to retroactive interference when participants are allowed to sleep after learning the original material, suggesting a sleep-related strengthening of memories. In the present study, we investigated delayed, long-term effects of sleep vs. sleep deprivation (SD) on the first post-training night on memory consolidation and resistance to interference. On day 1, participants learned a list of unrelated word pairs (AB), either in the morning or in the evening, then spent the post-training night in a sleep or sleep deprivation condition, in a within-subject paradigm. On day 4, at the same time of day, they learned a novel list of word pairs (AC) in which 50% of the word pairs stemmed with the same word than in the AB list, resulting in retroactive interference. Participants had then to recall items from the AB list upon presentation of the “A” stem. Recall was marginally improved in the evening, as compared to the morning learning group. Most importantly, retroactive interference effects were found in the sleep evening group only, contrary to the hypothesis that sleep exerts a protective role against intrusion by novel but similar learning. We tentatively suggest that these results can be explained in the framework of the memory reconsolidation theory, stating that exposure to similar information sets back consolidated items in a labile form again sensitive to retroactive interference. In this context, sleep might not protect against interference but would promote an update of existing episodic memories while preventing saturation of the memory network due to the accumulation of dual traces.     

Erasing Sensorimotor Memories via PKMζ Inhibition

Sensorimotor cortex has a role in procedural learning. Previous studies suggested that this learning is subserved by long-term potentiation (LTP), which is in turn maintained by the persistently active kinase, protein kinase Mzeta (PKMζ). Whereas the role of PKMζ in animal models of declarative knowledge is established, its effect on procedural knowledge is not well understood. Here we show that PKMζ inhibition, via injection of zeta inhibitory peptide (ZIP) into the rat sensorimotor cortex, disrupts sensorimotor memories for a skilled reaching task even after several weeks of training. The rate of relearning the task after the memory disruption by ZIP was indistinguishable from the rate of initial learning, suggesting no significant savings after the memory loss. These results indicate a shared molecular mechanism of storage for declarative and procedural forms of memory.     

Interaction of Sleep and Emotional Content on the Production of False Memories

Sleep benefits veridical memories, resulting in superior recall relative to off-line intervals spent awake. Sleep also increases false memory recall in the Deese-Roediger-McDermott (DRM) paradigm. Given the suggestion that emotional veridical memories are prioritized for consolidation over sleep, here we examined whether emotion modulates sleep’s effect on false memory formation. Participants listened to semantically related word lists lacking a critical lure representing each list’s “gist.” Free recall was tested after 12 hours containing sleep or wake. The Sleep group recalled more studied words than the Wake group but only for emotionally neutral lists. False memories of both negative and neutral critical lures were greater following sleep relative to wake. Morning and Evening control groups (20-minute delay) did not differ ruling out circadian accounts for these differences. These results support the adaptive function of sleep in both promoting the consolidation of veridical declarative memories and in extracting unifying aspects from memory details.