Ines Wilhelm

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.

System consolidation of memory during sleep

Over the past two decades, research has accumulated compelling evidence that sleep supports the formation of long-term memory. The standard two-stage memory model that has been originally elaborated for declarative memory assumes that new memories are transiently encoded into a temporary store (represented by the hippocampus in the declarative memory system) before they are gradually transferred into a long-term store (mainly represented by the neocortex), or are forgotten. Based on this model, we propose that sleep, as an offline mode of brain processing, serves the ‘active system consolidation’ of memory, i.e. the process in which newly encoded memory representations become redistributed to other neuron networks serving as long-term store. System consolidation takes place during slow-wave sleep (SWS) rather than rapid eye movement (REM) sleep. The concept of active system consolidation during sleep implicates that (a) memories are reactivated during sleep to be consolidated, (b) the consolidation process during sleep is selective inasmuch as it does not enhance every memory, and (c) memories, when transferred to the long-term store undergo qualitative changes. Experimental evidence for these three central implications is provided: It has been shown that reactivation of memories during SWS plays a causal role for consolidation, that sleep and specifically SWS consolidates preferentially memories with relevance for future plans, and that sleep produces qualitative changes in memory representations such that the extraction of explicit and conscious knowledge from implicitly learned materials is facilitated.

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.

Developmental Differences in Sleep's Role for Implicit Off-line Learning: Comparing Children with Adults

Sleep crucially contributes to the off-line consolidation of memories. Although this view was confirmed in numerous studies in adults, it is not known whether it can be generalized to sleep during development. Here, we examined effects of sleep on implicit memory formation considered of particular relevance in children, because brain structures underlying implicit learning develop earlier in ontogeny than structures supporting explicit learning. Subjects were 7- to 11-year-old children (n = 14) and 20- to 30-year-old adults (n = 12) tested on a serial reaction time task before (learning) and after (retest) equal length retention periods of overnight sleep and daytime wakefulness. At learning, after eight training blocks, all subjects had acquired implicit knowledge of the probabilistic rules underlying the sequential stimulus materials, as indicated by a substantial difference in response time to grammatical versus nongrammatical trials in two test blocks that followed the training blocks. At learning, this response time difference was greater in children (48.49 6.08 msec) than adults (28.02 3.65 msec, p < .01), but did not differ between sleep and wake retention conditions in either age group. Consistent with previous studies, retesting in the adults revealed that the reaction time differences between grammatical and nongrammatical trials increased by 9.78 4.82 msec after sleep, but decreased by 12.76 5.49 msec after the wake retention period (p < .01). Contrary to this finding in adults, sleep in children did not lead to an increase, but to a decrease in the reaction time difference averaging 26.68 12.25 msec (p < .05), whereas across the wake retention interval the reaction time difference remained nearly unchanged. The sleep-dependent deterioration in measures of implicit sequence knowledge in children was in striking contrast to the gain of such knowledge in the adults during sleep (p < .01). Our findings indicate that the functional role of sleep in implicit memory consolidation depends on age. We speculate that the overnight decrease of implicit knowledge in children reflects a preferential effect of sleep toward the enhancement of explicit aspects of task performance that interferes with implicit performance gains.

The sleeping child outplays the adult's capacity to convert implicit into explicit knowledge

When sleep followed implicit training on a motor sequence, children showed greater gains in explicit sequence knowledge after sleep than adults. This greater explicit knowledge in children was linked to their higher sleep slow-wave activity and to stronger hippocampal activation at explicit knowledge retrieval. Our data indicate the superiority of children in extracting invariant features from complex environments, possibly as a result of enhanced reprocessing of hippocampal memory representations during slow-wave sleep.

Sleep-dependent consolidation of procedural motor memories in children and adults: the pre-sleep level of performance matters

In striking contrast to adults, in children sleep following training a motor task did not induce the expected (offline) gain in motor skill performance in previous studies. Children normally perform at distinctly lower levels than adults. Moreover, evidence in adults suggests that sleep dependent offline gains in skill essentially depend on the pre-sleep level of performance. Against this background, we asked whether improving childrens performance on a motor sequence learning task by extended training to levels approaching those of adults would enable sleep-associated gains in motor skill in this age group also. Children (4-6 years) and adults (18-35 years) performed on the motor sequence learning task (button-box task) before and after ~2-hour retention intervals including either sleep (midday nap) or wakefulness. Whereas one group of children and adults, respectively, received the standard amount of 10 blocks of training before retention intervals of sleep or wakefulness, a further group of children received an extended training on 30 blocks (distributed across 3 days). A further group of adults received a restricted training on only two blocks before the retention intervals. Children after standard training reached lowest performance levels, whereas in adults performance after standard training was highest. Children with extended training and adults after reduced training reached intermediate performance levels. Only at these intermediate performance levels did sleep induce significant gains in motor sequence skill, whereas performance did not benefit from sleep in the low-performing children or in the high-performing adults. Spindle counts in the post-training nap were correlated with performance gains at retrieval only in the adults benefitting from sleep. We conclude that, across age groups, sleep induces the most robust gain in motor skill at an intermediate pre-sleep performance level. In low-performing children sleep-dependent improvements in skill may be revealed only after enhancing the pre-sleep performance level by extended training.

Generalization of word meanings during infant sleep

Sleep consolidates memory and promotes generalization in adults, but it is still unknown to what extent the rapidly growing infant memory benefits from sleep. Here we show that during sleep the infant brain reorganizes recent memories and creates semantic knowledge from individual episodic experiences. Infants aged between 9 and 16 months were given the opportunity to encode both objects as specific word meanings and categories as general word meanings. Event-related potentials indicate that, initially, infants acquire only the specific but not the general word meanings. About 1.5 h later, infants who napped during the retention period, but not infants who stayed awake, remember the specific word meanings and, moreover, successfully generalize words to novel category exemplars. Independently of age, the semantic generalization effect is correlated with sleep spindle activity during the nap, suggesting that sleep spindles are involved in infant sleep-dependent brain plasticity.

Contribution of norepinephrine to emotional memory consolidation during sleep

BACKGROUND There is increasing evidence indicating that slow wave sleep (SWS) supports memory consolidation. This effect may in part originate from phasic noradrinergic (NE) activity occurring during SWS in the presence of tonically lowered NE levels. Here, we examined whether NE supports the consolidation of amygdala-dependent emotional memory during SWS. METHODS In a double-blind cross-over study, 15 men learned emotional and neutral materials (stories, pictures) in the evening before a 3-h period of early SWS-rich retention sleep, during which either placebo or clonidine, an α2-adrenoceptor agonist which blocks locus coeruleus NE release, was intravenously infused. Memory retrieval as well as affective ratings and heart rate responses to the pictures were assessed 23 h after learning. RESULTS Clonidine reduced plasma NE levels but had no effect on SWS. While retention of story content words and pictures per se remained unaffected, clonidine distinctly blocked the superiority of emotional compared to neutral memory for temporal order, with this superiority of emotional over neutral memories observed only in the placebo condition. Heart rate responses to pictures were not affected, but whereas under placebo conditions familiar negative pictures were rated less arousing and with a more negative valence compared to pictures not seen before; these differences were abolished after clonidine. CONCLUSION Given that memory for the temporal order of events depends on the hippocampus to a greater extent than item memory, our findings suggest that NE activity during early SWS-rich sleep facilitates consolidation of memories that involve both, a strong amygdalar and hippocampal component.

Reduced sleep-associated consolidation of declarative memory in attention-deficit/hyperactivity disorder

OBJECTIVE Sleep supports the consolidation of declarative memory. Patients with attention-deficit/hyperactivity disorder (ADHD) are not only characterized by sleep problems but also by declarative memory deficits. Given that the consolidation of declarative memory during sleep is supported by slow oscillations, which are predominantly generated by the prefrontal cortex, and that ADHD patients display low prefrontal brain activity, we assumed that ADHD patients show reduced sleep-associated consolidation of declarative memory. METHODS The impact of sleep on the consolidation of declarative memory was examined with a picture recognition task. Twelve ADHD patients (10-16 years) and 12 healthy controls participated in two experimental conditions: in the sleep condition, learning was performed in the evening and picture recognition was tested after nocturnal sleep; in the wake condition, learning was conducted in the morning while retrieval took place after a day of wakefulness. RESULTS Analyses of recognition accuracy revealed reduced sleep-associated enhancement of recognition accuracy in ADHD. While sleep-associated enhancement of recognition accuracy was correlated with slow oscillation power during non-REM sleep in healthy controls, no such correlations were observed in ADHD. CONCLUSIONS These data indicate a deficit in sleep-associated consolidation of declarative memory in ADHD. Moreover, our results suggest reduced functionality of slow oscillations in sleep-associated consolidation of declarative memory in ADHD.