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Memory Processing in Relation to Sleep Philippe Peigneux and Carlyle Smith Abstract Although each of us empirically recognizes the utmost importance of sleep for the quality of our everyday life, its functions have long remained shrouded in mystery. Beyond its putative physiologic functions, there is now growing evidence that sleep plays a prominent role in brain plasticity and in memoryconsolidation processes. According to this proposal, memory traces formed during a learning episode are not immediately stored in their definitive form. Rather, they are initially kept in a labile, fragile state, during which they can be easily disrupted. Over time and especially during sleep, they subsequently undergo a series of transformations during which they will be consolidated and fully integrated into long-term memory. In this chapter, we present experimental data that provide support for the hypothesis that sleep exerts a promoting effect on plastic processes of memory consolidation. Some studies have assessed the effects of posttraining sleep deprivation on memory consolidation and on the reorganization of the neural substrates of long-term memories. Others have investigated the effects of learning on posttraining sleep and In 1867, Hervey de Saint Denys, fascinated by his dreams since the age of 14, published Les Rêves et les Moyens de les Diriger.1 In his book, he reported a series of ingenious experiments showing that experienced events are incorporated into our dreams, in which they can be combined to create original associations between “memory images” of the past. Hence, he strongly opposed the idea that sleep may be a sudden drop in a state of cognitive “non-being” in which our resting brain is disconnected. On the contrary, he claimed that “a sleep without dreams cannot exist, just as a wake state without mentation does not exist.” Besides dreaming activity, however, addressed in Section 7 of this book, we know that the sleeping brain houses a wide set of cognitive processes, including the ongoing treatment of elaborated external stimuli, the revival of experiences, and last, but not least, the consolidation of new information in memory. Interestingly, recognition that persistence of mental activity in the sleeper may be an integral part of the physiologic processes that subtend memory consolidation arose only in the last quarter of the 20th century. The hypothesis had to wait till now to receive widespread acknowledgement, as illustrated by the fact that for the first time a chapter devoted to sleep in relation to memory has been introduced in this fifth edition of Principles and Practices in Sleep Medicine. This chapter introduces the issues surrounding the role that sleep may play in memory consolidation, focusing on human data. Reviews about relationships between sleep and memory in animals are addressed can be found elsewhere.2-4 We will here outline key findings and milestones in probing the sleep-for-memory hypothesis, as well as ongoing debates and thoughtful questions that remain. Chapter 29 reexpression of behavior-specific neural patterns during posttraining sleep, and still others have probed the effects of within-sleep stimulation on sleep patterns and overnight memories. Besides-demonstrating a role of sleep in memory consolidation processes, these studies have also indicated that sleep stages are functionally different, in that they may subserve distinct memory processes. Available evidence reveals complex interactions between sleep and memory systems, in agreement with the fact that memory is a complex construct of specialized memory subdomains, and that sleep is composed of distinct stages characterized by specific physiologic mechanisms. Despite advances that have refined our understanding of the relationships between sleep and cognitive processes, the underlying mechanisms still remain to be fully elucidated. Further steps are now required to understand how sleep disorders and pathologies accompanied by sleep disturbances affect cognitive functions, and especially learning and memory consolidation in humans, eventually leading to remedial interventions. Before approaching the subject, however, we will briefly introduce the concepts of memory consolidation and memory systems in humans. Previous chapters have shown that sleep is a multidimensional state of vigilance, composed of rapid eye movement (REM) and non-REM (NREM) episodes that present distinctive features and rely on specific neuroanatomic substrates.4 From both cognitive and neurophysiologic perspectives, memory is not a unitary phenomenon. Rather, memory should be seen as a generic concept for information storage, encompassing a series of specific subdomains.5 Consequently, the interaction between multidimensional states of sleep and distinctive memory systems makes it logical that not all sleep manipulations will have the same impact on performance, depending on the various parameters embedded in the memory task.2,6,7 We will examine the growing number of behavioral studies that have enlightened our understanding of the role played by sleep episodes in memory consolidation. The rapid evolution of neurophysiologic techniques and analytical approaches allows scrutiny of the complex relations between cognitive processes and their underlying neural substrates. Part of this chapter will focus on the neurophysiologic mechanisms acting in sleep to support, or at least favor, memory consolidation processes. Molecular biology of memory consolidation is beyond the scope of this chapter and is reviewed elsewhere.4 The relationship between consolidation of learning and sleep is a crucial issue because memory is at the root of most of our daily behaviors, such as simple skill acquisition (e.g., typewriting), sophisticated operational procedures (e.g., using computer-based systems), and keeping track of personal events and relationships. 335 Kryger_6453_Ch 29_main.indd 335 8/24/2010 7:23:50 PM L 336 PART I / Section 4 • Physiology in Sleep MEMORY SYSTEMS AND MEMORY CONSOLIDATION We are able to learn, store, and remember various types of information in different ways and for variable periods of time, from conscious acquisition strategies to incidental detection of environmental events. Cerebral damage can selectively alter some of these processes while leaving others undisturbed. These simple observations have led to the proposal that memory is not a unitary phenomenon but rather a complex construct of more or less specialized memory subdomains.5 First, a seminal distinction that dates back to William James is made between short- and long-term memory stores. The former is dedicated to the temporary storage of volatile information for up to seconds, whereas the latter, the main focus in this chapter, houses potentially lasting information that is deemed consolidated and less susceptible to disruption. Long-term memories in humans may further belong to multiple systems, primarily delineated between declarative and nondeclarative memories (Fig. 29-1). Distinguishing features of declarative memory are that information is easily accessible to verbal description and that encoding or retrieval is usually carried out explicitly— that is, the subject is aware that the stored information exists and is being accessed. Declarative memory is further composed of semantic and episodic memory components. Semantic memory is the receptacle for our general knowledge about the world, regardless of the spatiotemporal context of knowledge acquisition (e.g., we know that Paris is the capital of France, and that fuel is combustible, but we are probably unable to recollect how and when we learned these facts). Episodic memory, on the other hand, refers to the system that stores events and information along with their contextual location in time and space (e.g., I can vividly remember having visited the British Museum with my cousin on a rainy day in the fall of 1993). Declarative memory Emotion Episodic memory Semantic memory Personally experienced events, spatial and temporal memory features Facts and concepts about the world, general knowledge Nondeclarative memory L Skills and habits Priming Conditioning “How to” knowledge, perceptual, motor and cognitive abilities Processing facilitation after prior exposure Elementary associative memory Figure 29-1 Schematic organization of long-term memory systems. Kryger_6453_Ch 29_main.indd 336 Distinctive features of nondeclarative memories are that they are not easily accessible to verbal description and can be acquired and reexpressed implicitly. Thus, our behavioral performance can be affected by the new memory even if we are not consciously aware that new information has been encoded or is being retrieved. Memory abilities aggregated under the nondeclarative label also gather different forms: skills, habits, priming, and conditioning. Although grouped under the nondeclarative label, these various processes are subtended by distinct neuroanatomic substrates in both humans and animals, further suggesting their relative independence.5 Besides the transverse division between long-term memory subsystems proposed by these influential models, there is a dynamic longitudinal process. Newly acquired information is not immediately stored at the time of learning in its final form, if such a stable state exists. Rather, memories undergo a series of transformations over hours, days, or even years, during which time they are gradually incorporated into preexisting sets of mnemonic representations,8-10 or are subjected to forgetting.11 This is the concept of memory consolidation, which can be defined as the time-dependent process that converts labile memory traces into more permanent or enhanced forms.12 These transformations are made possible by our brain plasticity—that is, the capacity of the brain to modify its structure and function over time, within certain boundaries.13 Eventually, time-dependent processes of consolidation and the ensuing robust memory trace will enduringly adjust the behavioral responses to the recent environmental changes, thereby enlarging the organism’s behavioral repertoire.14 Scientific evidence suggests that sleep and the associated processes of brain plasticity4 are major players in timedependent processes of memory consolidation, acting as key constituents in the chain of transformations that help integrate information for the long term. Furthermore, these studies suggest that distinct sleep stages may have distinct memory-related functions, which has been interpreted in two different but nonexclusive ways. According to the dual-process hypotheses, REM and NREM sleep act differently on memory traces depending on the memory system or process to which they belong. For example, it has been proposed that slow-wave sleep (SWS)—the deepest stage of NREM sleep—facilitates consolidation of declarative and spatial memories, whereas REM sleep facilitates consolidation of nondeclarative memories.15,16 Another interpretation is that particular sequences of sleep states reflect the succession of brain processing events supporting memory consolidation.17 An example is the proposal that REM sleep actively consolidates or integrates complex associative information, whereas NREM sleep passively prevents retroactive interference of recently acquired complex associative information.18 In this view, SWS and REM sleep play complementary roles and have to act serially to consolidate the new memory trace, in a double-step process.19,20 Both approaches assume that it is sleep on the first posttraining night that is important for memory consolidation. Nonetheless, it would be premature to claim that only sleep may achieve the necessary conditions to consolidate novel memories in the nervous system, as both sleeplike cognitive and neural processes of 8/24/2010 7:23:50 PM memory consolidation have also been observed during wakefulness.21-23 METHODS FOR STUDYING THE ROLE OF SLEEP FOR MEMORY CONSOLIDATION Three experimental approaches have been used to test the hypothesis that sleep exerts a favorable or promoting effect on memory consolidation. These approaches focus on (1) the effects of posttraining sleep deprivation on memory consolidation and on the reorganization of the neural substrates of long-term memories, (2) the effects of learning on posttraining sleep and reexpression of behavior-specific neural patterns during posttraining sleep, or (3) the effects of within-sleep stimulation on sleep patterns and overnight memories. Posttraining Sleep Deprivation The first and probably most ancient line of investigation has probed the putatively detrimental effect of sleep deprivation on the night after learning, based on the assumption that memory performance over the long term will be better if participants are allowed to sleep after learning rather than being deprived of sleep. In classic procedures, subjects learn new material. Afterward, some participants are allowed to sleep normally whereas others either do not sleep at all (total sleep deprivation), are awakened at the onset of occurrences of the sleep stage under study (selective sleep deprivation), are kept awake during the period of the night in which the sleep stage is predominant (partial sleep deprivation), or have a shortened sleep duration (sleep restriction). Finally, prenight and postnight memory measures are compared between sleeping and sleepdeprived subgroups, either the next day or several days later. Jenkins and Dalenbach24 used this approach about 85 years ago and found that the forgetting curve for newly learned verbal material described by the German psychologist Ebinghaus was significantly dampened by the presence of an intermediate period of sleep. Nonetheless, they did not attribute this effect to a specific role of sleep per se in memory processing but merely to the protective role that sleep may have against “interference, inhibition, or obliteration of the old by the new.”24 However, this hypothesis of a purely passive role for sleep in memory processes has been challenged by studies of selective sleep deprivation that attribute a specific role to REM sleep in memory storage and consolidation, in both human and animal species.25 Also, it was demonstrated that memory over an interval with relatively high amounts of stage 4 sleep (i.e., in the first half of the night) was superior to memory over an interval with relatively high amounts of REM sleep (i.e., in the second half of the night).26 This seemingly apparent contradiction was resolved later, with the demonstration that recall of paired-associate lists was significantly better after sleep than wakefulness in the first part of the night only, whereas consolidation of mirrortracing skills specifically benefited from sleep in the second part of the night.15 Results showed that memories belonging to the declarative and nondeclarative systems do not benefit from the same sleep components. Other experimental manipulations inferred a specific role for stage 2 Kryger_6453_Ch 29_main.indd 337 CHAPTER 29 • Memory Processing in Relation to Sleep 337 sleep in the second part of the night for the consolidation of motor memories.27,28 Hence, sleep deprivation studies have suggested that each stage of human sleep (REM sleep, SWS, stage 2 sleep) might be involved in a distinctive way in learning and memory consolidation processes.6,7 In the recent past, neuroimaging investigations have complemented these findings using functional magnetic resonance imaging (fMRI). As in behavioral paradigms, subjects are trained to the task and then either deprived of sleep or allowed to sleep on the following night. A few days later, cerebral activity is recorded during memory retrieval and the two posttraining sleep conditions are compared. One or two additional nights of regular sleep are usually allowed after the posttraining night before testing in the scanner, to avoid different arousal states that may confound neural activity associated with memory retrieval between sleeping and sleep-deprived subjects. These neuroimaging studies have yielded two important contributions. First, they have demonstrated that sleep deprivation during the posttraining night eventually impedes the reorganization and optimization of the cerebral activity, subtending delayed retrieval of consolidated memories during wakefulness.29-32 Second, they have shown that sleepdependent changes in memory-related brain activity patterns may be present even when similarity in behavioral performance between posttraining sleep conditions suggests an absence of sleep-related effect on memory.30,32 The latter results further indicate that long-term memory performance can be achieved using different cerebral strategies initiated as a function of the status of sleep during the posttraining night. Posttraining Sleep Modifications The second line of investigation stemmed from the reasoning that if newly acquired information underwent an ongoing process of consolidation during sleep, then this should be reflected in neural and physiologic features of posttraining sleep. Using electroencephalographic (EEG) recording techniques, numerous animal studies have reported changes in, or memory-related associations with, a series of postlearning sleep parameters, including sleep stage duration or proportion relative to total sleep time, density of rapid eye movements, power increase in selected EEG frequency ranges, changes in density and duration of phasic events (e.g., spindles, ponto-geniculo-occipital waves), and reexpression of learning-specific neural patterns (for reviews, see references 3, 4, 6, 33, 34). Likewise, in humans, numerous EEG studies have evidenced that both the architecture of sleep and distinctive features of sleep stages can be affected by prior learning experience. For example, postlearning sleep modifications have been shown when looking at absolute or proportional (i.e., relative to total sleep time) increases in the duration of REM sleep,6,20,35-37 stage 2 sleep38 and SWS20 episodes. Other studies have reported increased density of rapid eye movements39,40 and stage 2 spindle activity in the sigma frequency band,41-50 as well as increases in REM sleep theta power.51 Many found statistical correlations between quantitative parameters of sleep and overnight performance improvements20,37,41-44,48-50 or levels of performance at the end of learning,45 suggesting a close link between changes in sleep physiology and memory consolidation. In support 8/24/2010 7:23:50 PM L 338 PART I / Section 4 • Physiology in Sleep of the double-step hypothesis described earlier, others studies evidenced relationships between performance changes and the organization of NREM/REM sleep cycles.19,52 Hence, these investigations, mostly based on noninvasive electrophysiologic techniques, have consistently demonstrated that physiology of sleep is influenced by prior learning during the day. Additionally, waking experience was shown to influence the content of hypnagogic hallucinations53 and of dreams collected on awakening from sleep stages54,55 on the postexposure night, although delayed incorporations of up to weeks have also been reported often.55 Noninvasive neuroimaging studies, especially using positron emission tomography (PET) measurements, with their better spatial resolution and whole brain coverage, have been used to look more precisely at the neural correlates of postlearning modifications during sleep. They have shown that neural activity occurring during waking task practice in learning-dedicated cerebral structures can be reexpressed or continued during both REM56,57 and NREM58 stages of sleep, as well as during posttraining wakefulness.21 These data were in close agreement with intracerebral recording studies in animals, which demonstrated neuronal reactivation during sleep.59,60 The animal data suggested reactivation of coherent memory traces in key cerebral structures during sleep that was deemed to contribute to or reflect the result of the memory consolidation process. However, these seminal animal studies did not experimentally establish the behavioral relevance of reactivations in neuronal ensembles, as they never sought to show a relationship with subsequent behavioral modifications. A significant contribution of human neuroimaging data was to show that experience-dependent reactivations of local—that is, hippocampal—activity during SWS are correlated to overnight gains in memory performance after spatial navigation.58 On the other hand, levels of implicit procedural learning achieved before sleep correlated with the amplitude of reactivation in cortical areas during REM sleep,57 at which time connectivity patterns between learning-related areas were additionally reinforced.61 Taken together, human reactivation studies have suggested the neuronal replay of previous experience during sleep, and that posttraining sleep activity in brain areas involved during the learning episode represents a neural signature of memory-related cognitive processes. Another (but not exclusive) hypothesis is that learning in the awake state induces local synaptic changes that themselves induce local changes in slow-wave activity (SWA), the main marker of sleep homeostasis, and that these changes are ultimately beneficial to imprint novel memories.62 In support of this view, high-density electrophysiologic recordings have demonstrated local increases in SWA in learning-related areas during posttraining NREM sleep, correlating with overnight performance improvements.63 L Within-Sleep Stimulations Finally, a third approach to demonstrate memory processing during sleep has been to provide specific stimulations during sleep with the aim of investigating whether meaningful stimuli could be recognized or new associations formed, or whether presleep learning can be modified by nonawakening stimulations. Evidence for such phenomena Kryger_6453_Ch 29_main.indd 338 would indicate that active plastic processes are taking place during sleep. In line with animal studies,33 preliminary data have indicated the possibility of heart rate conditioning in man during NREM sleep,64 suggesting plasticity during sleep. On the other hand, no learning effect was found for lists of paired-associate words presented during either REM or stage 2 sleep and tested immediately afterward.65 Although these results suggest a limitation in learning capacity during sleep, there is consistent evidence that sleeping subjects remain able to detect and discriminate external sensory events as indexed by event-related auditory potentials (ERPs).66,67 Likewise, nociceptive stimulations during sleep persistently elicit evoked responses.68 ERP and fMRI data also indicated higher sensitivity to external stimuli during tonic than phasic periods of REM sleep.69,70 Higherlevel processing of externally presented events was also found during sleep, as auditory ERPs are elicited after hearing one’s own name both while sleeping and awake.71 Nonetheless, brain responsiveness during sleep is not independent of prior waking experience. Learning semantic associations72 or discriminating auditory patterns67 during wakefulness leads to changes in evoked response potentials during sleep,72 even up to 2 days later.67 These results support the idea that external events can be processed during certain periods of sleep, and that stimulus significance affects this processing. Further demonstrating an active role for sleep in memory consolidation processes, several studies have established that stimulations in the posttraining sleep period may enhance performance as compared with a standard, unmodified posttraining night.73-77 Presentation of nonawakening auditory stimulations during REM sleep after Morse code learning73 or re-presentation during REM sleep of sounds heard in background while learning a complex logic task74 increased overnight memory. This effect was present only when auditory stimulations were displayed in coincidence with the bursts of rapid eye movements that reflect phasic ponto-geniculo-occipital (PGO) activity in man. Likewise, presentation during SWS of odors that were used as contextual cues during the learning episode triggered hippocampal responses and improved overnight retention of declarative memories.77 Transcranial direct-current stimulation that modulates excitability in cortical areas improved declarative memory when applied during SWS,76 especially when application of oscillating potentials at about 0.75 Hz induced slow oscillationlike potential fields that mimic the slow oscillations of deep NREM sleep.75 Finally, artificially maintaining high levels of cortisol feedback and cholinergic tone during SWS impairs hippocampus-dependent declarative memory formation,78-80 suggesting that the natural shift in central nervous system cholinergic tone from high levels during acquisition-related wakefulness periods to minimal levels during SWS optimizes declarative memory consolidation.81 On the other hand, preventing natural increases in cortisol during REM sleep periods appears to enhance amygdala-dependent emotional memory.80 These studies have demonstrated beneficial (or detrimental) effects of various stimulations and manipulations in the posttraining sleep periods on overnight gains in performance, and therefore have provided interesting evidences that sleep 8/24/2010 7:23:50 PM CHAPTER 29 • Memory Processing in Relation to Sleep 339 does not play a merely passive role in memory processing by protecting novel memories from interference. Rather, they support the hypothesis that sleep acts in a complex manner in providing optimal conditions for the consolidation of novel memories in the nervous system. mPFC sites when initial encoding was followed by a night of sleep than by sleep deprivation, suggesting that sleep leads to long-lasting changes in the representation of memories at the neuroanatomic level.31 These results may be consistent with the hypothesis that sleep exerts an effect on the gradual semanticization of the learned material. SLEEP AND DECLARATIVE MEMORY As discussed, long-term declarative memory comprises semantic and episodic memory components. Experimental data indicate that the role of sleep in consolidating these two memory components may be dissociated to a certain extent, and that emotional variables play a modulatory role in episodic memory consolidation. These aspects will be covered in the following section. Episodic Memory The effect of sleep on episodic memory has been extensively studied using a series of declarative memory paradigms encompassing learning of verbal material such as lists of words or paired-associate words15,31,41,42,50,51,75,76,78,79,84-89 and sentences or prose passages,90 and explicit encoding of landscapes,83 objects’ locations,77 faces,91 visuospatial memory,16,48 and navigation in virtual30,32,58,92 or natural93 environments. Among these, most studies using partial behavioral15,16,31,85 or pharmacologic79 sleep deprivation have consistently found that SWS, or at least the first half of the night of sleep (which is rich in SWS), is beneficial for the consolidation of novel declarative memories. Consolidation of declarative learning was also linked to increased spindle activity during posttraining stage 2 sleep,41,42,48-50 as well as to the alteration of SWS94 and spindles95 in schizophrenia. Spindles are strong candidates to subtend memory consolidation processes during sleep because they are thought to support neural plasticity.96 As well, declarative learning abilities have been linked with increased spindle activity during stage 2 sleep44,97 and periodic arousal fluctuations during non-REM sleep98 in healthy subjects. On the other hand, declarative memory deficits are associated with decreased sleep spindle activity in patients with Alzheimer’s disease,99 and NREM sleep duration and number of cycles in patients with chronic nonrestorative sleep.100 However, others reported that overnight performance gains on declarative verbal memory depend primarily on preserved organization of sleep cycles—that is, sleep continuity—rather than on the integrity of a specific sleep stage per se.19 These studies may stand in contrast with much older ones that showed impairment in recall of sentences and short stories101 or lists of words102 after selective REM sleep deprivation. Also, a more recent study found that REM sleep deprivation specifically impaired recall of spatial and temporal features of memories, as well as the subject’s confidence in his own remembering,89 these parameters being considered as genuine components of episodic memory, as opposed to general recall, which may partially rely on semantic, decontextualized memories.2 Accordingly, it has been reported that consolidation during sleep enhances explicit recollection in recognition memory103 and strengthens the original temporal sequence structure for lists of triplet words.104 Semantic Memory Few studies have looked at the role of sleep for consolidation of semantic information, although ERP studies have demonstrated that semantic processing of externally presented stimuli is possible during REM and stage 2 sleep, but not during SWS.66,71,72 Also, it has been shown that the semantic priming (i.e., the facilitatory processing effect resulting from prior presentation of semantically related material) qualitatively differs upon awakening from stage 2 and REM sleep.82 Despite evidence for residual semantic processing, attempts to create novel semantic associations using direct auditory stimulation during sleep have been unsuccessful.65 Other evidence for a role of sleep in processing newly acquired semantic memories are not fully conclusive because the tasks that have been used comprise other cognitive components that may obscure the interpretation.2 For example, improvement in a French immersion course over 6 weeks was correlated with REM sleep increases,36 but learning a novel language is a task that involves episodic memory processes as well as the creation of novel semantic associations. Likewise, learning Morse code, which was found to be associated with increases in REM sleep parameters,37 may be viewed as a specific form of cognitive procedural learning of novel associations. Also, it is believed that transfer of novel information from hippocampus-dependent episodic memory stores to neocortical, semantic, decontextualized memory representations is a gradual process that may take years to complete.8 Therefore, protocols in which initial encoding, posttraining sleep periods and retrieval are temporally close are probably not best suited to segregate the semantic component of memory from other constituents. A few neuroimaging studies have investigated the cerebral correlates of declarative memory retrieval after extended periods of time (up to 6 months) using pairedassociate list of words31 or pictures of landscapes.83 Although these experiments were not specifically designed to probe whether the memorized material was semanticized at the time of retesting, neuroimaging results clearly indicated a transfer from activity in hippocampal locations, observed early after learning, toward activity in medial prefrontal cortical (mPFC) sites recorded 6 months later during memory retrieval.31,83 Furthermore, total sleep deprivation on the postlearning night hindered this gradual process of consolidation. Six months after learning verbal material, memory retrieval more strongly activated the Kryger_6453_Ch 29_main.indd 339 Emotion in Episodic Memory The role of emotional variables in sleep-dependent processes has been a focus of recent interest.80,90,105-108 Emotion can be seen as an important contextual cue in retention of episodic memories, although it is not necessarily processed explicitly. Nonetheless, emotional material was found to be better recalled after REM than after NREM sleep90 and to be altered after sleep deprivation,105 although more for the emotional content than the context of the 8/24/2010 7:23:50 PM L 340 PART I / Section 4 • Physiology in Sleep information.108 However, others have found emotional memories to be better preserved, or at least less disrupted, than neutral memories after total sleep deprivation.80,106 These latter results suggest that consolidation of emotional memories also occurs efficiently during awake periods, an effect that may be explained by the important ecologic value of rapidly acquiring emotional stimulus– response associations. Similarly, it was found that sleep deprivation does not alter behavioral performance in an ecologically valid virtual navigation task.30,32 Importantly, a lack of behavioral effect does not guarantee that sleep was without any consequence on memory consolidation processes, as, in the case of both navigation and emotional memories, underlying patterns of brain activity at retrieval were effectively altered by sleep deprivation on the posttraining night.30,32,106 SLEEP AND NONDECLARATIVE MEMORIES As mentioned, memory abilities aggregated under the nondeclarative label may be relatively independent from both cognitive and neuroanatomic standpoints.5 Skills and habits that refer to the gradual acquisition of novel perceptual, motor, and cognitive abilities through repeated practice (e.g., discriminating figures, playing piano, riding a bicycle, detecting environmental regularities) have been the most widely investigated in relation to sleep. In this respect, numerous studies have found that posttraining sleep boosts acquisition levels on nonverbal motor,35,46,109-115 perceptual,20,54,116-124 and perceptual– motor15,27,29,43,45,56,57,61,63,125-129 procedural learning tasks. Additionally, a few studies have found that sleep particularly enhances procedural memory performance in brain-damaged individuals,130,131 but not in patients suffering from degenerative Parkinson’s disease,132 suggesting the importance of sleep in motor rehabilitation programs. Next, we further describe the role of sleep in (1) perceptual, (2) motor, and (3) perceptual–motor learning, and (4) priming. L Sleep and Perceptual Learning One of the most consistent findings in the literature is the prominent role of sleep in the development of visual discrimination abilities. Most studies have used the texture discrimination task initially proposed by Karni and Sagi,133 where learning is retinotopic (i.e., specific to the trained visual quadrant).20,116,120-124 It was initially found that selective REM sleep deprivation, but not SWS deprivation, abolished overnight performance improvement during visual perceptual learning, whereas no or only feeble improvements occurred over episodes of wakefulness.133 However, another study using the same task found that improvement in visual discrimination skills was mostly disrupted by early sleep deprivation (i.e., rich in SWS), and even more so by total sleep deprivation.116 This apparent contradiction was partially resolved with the finding that overnight improvement was a direct function of both the amount of SWS in the first quarter of the night and the amount of REM sleep in the late quarter of the night,20 suggesting that SWS prompts memory formation, which is possibly, but not necessarily, consolidated during REM Kryger_6453_Ch 29_main.indd 340 sleep. There is further evidence of the complementary roles of sleep stages in the offline (i.e., occurring outside of actual practice) processes of consolidation for visual perceptual learning. Indeed, others have found that repeated practice on a task within the same day does not lead to any improvement and can even result in performance deterioration for the trained visual quadrant, unless there is an intervening sleep episode.123 But most importantly, they demonstrated that the duration of the sleep episode and its constituent phases is crucial in this process, as 30-minute daytime naps merely discontinued performance deterioration over repeated sessions,123 60-minute naps reverted performance to its original level,123 and 90-minute naps yielded improvement in discrimination performance.122 The main differences were more time spent in NREM sleep in the 60-minute nap than in the 30-minute nap, and the occurrence of REM sleep in the 90-minute nap. Other studies confirm the importance of posttraining sleep in the consolidation of coarse visual discrimination119 as well as the effect of visual adaptation paradigms on subsequent sleep parameters,54 thus demonstrating the importance of both REM and NREM sleep stages for consolidation of procedural abilities in the visual system. However, sleep-dependent improvements cannot yet be fully generalized across modalities, as contradictory results have been reported in the auditory domain. Whereas some authors have reported a beneficial influence of sleep on acquisition of auditory discrimination skills118,134 and perceptual generalization of phonologic categories,117 others have found that the same amount of time spent in the awake state is sufficient to allow the development of auditory identification abilities.135,136 With respect to more sophisticated auditory discrimination abilities, however, it has been shown that integration of newly learned spoken word forms, which must be discriminated from similarsounding entries during auditory word recognition, requires an incubation-like period containing sleep.137 Sleep and Motor Learning Using a simple sequential thumb-to-fingers opposition task, Karni and coworkers investigated the time-dependent evolution of motor learning.10 They showed that skilled performance on this task is acquired across an initial, within-session, fast learning phase, followed by a slow phase of consolidation and optimization that can extend for several weeks of repeated practice. Using the same task or a keyboard-presses variant, others subsequently found that posttraining sleep significantly enhanced performance in the absence of further practice, as compared with the same amount of time elapsed awake.46,109,111,112 However, contrary to the observations made using perceptual visual discrimination tasks described in the prior section, it cannot be claimed here that posttraining time spent awake prevents the formation of long-term motor memories, as performance merely stabilizes at the level achieved at the end of learning and does not deteriorate but rather modestly improves over repeated practice sessions. Still, a transitory boost in performance that is observed 5 to 30 minutes after the end of learning138 disappears if tested without an intermediate sleep period more than 4 hours later.46,138 Interestingly, performance improvement over the 5- to 8/24/2010 7:23:50 PM 30-minute boost predicts performance levels after a night of sleep.138 This precocious posttraining period appears important for the initial stabilization of motor memories,21 as learning an interfering sequence of movements during 30 minutes to 2 hours after training disrupts delayed, sleep-dependent consolidation of the original material,109,114 unless a nap is allowed.114 This role of sleep for motor memory consolidation extends beyond a genuine motor component, as training-related changes in sleep architecture are observed after practice of a sequence of finger movements but not after random key-presses,110 as well as after acquiring new and complex motor patterns such as trampolining35,115 but not after the familiar and well-learned motor activities of soccer or dancing.115 These latter results are in line with the demonstration that sleep provides maximal benefit for motor-skill procedures that proved to be most difficult during learning.113 Motor learning–related changes in posttraining sleep parameters were mostly observed during stage 2 sleep,46,110,111 although others have reported links with REM sleep115,139 or sleepcycle organization.35 Further studies are needed to delineate precisely the role and benefit of sleep on motor learning. Sleep and Perceptual–Motor Learning The motor learning tasks just described have definite features. They are self-initiated, and acquisition is initially carried out in an explicit, almost declarative manner, as the motor sequence of movements to be generated is already known and can even be verbalized. In this respect, motor procedural learning reflects the optimization of predefined motor forms possibly created with the con tribution of episodic memory processes. In contrast, perceptual–motor procedural learning entails a motor performance triggered by external stimulations, but the organization of the material to be learned is not necessarily obvious to the subject, although it affects its performance. This type of task potentially allows us to distinguish the role of sleep for consolidation of unconsciously as opposed to consciously formed memories. We will cover this aspect after reviewing perceptual–motor studies. It was initially found that performance improvement on the pursuit rotor task was blocked by total sleep deprivation and by sleep deprivation of the second part of the night, but not by selective REM sleep deprivation.27 Task improvement was also associated with increased sleep spindle activity,45,51 suggesting that consolidation of motor adaptive memories is mostly dependent on stage 2 sleep. Functional MRI additionally showed that posttraining total sleep deprivation hampered both performance improvement and the reorganization of brain activity on a visuomotor pursuit task with hidden regularities in the target’s trajectory.29 However, mirror-tracing skills were reported to improve more during the late part of the night,15 and to be associated with REM sleep increases in well-performing individuals,51 suggesting that this latter task is rather REM sleep dependent. Still, performance improvement on mirror tracing was also found to occur after naps dominated by stage 2 sleep125 and to correlate with stage 2 sleep spindle activity.43 This apparent discrepancy between sleep stages and task associations in the Kryger_6453_Ch 29_main.indd 341 CHAPTER 29 • Memory Processing in Relation to Sleep 341 perceptual–motor learning domain might be explained by differences in initial skill levels of participants. Indeed, an association was reported between performance improvement on the pursuit rotor task and stage 2 spindle activity in highly skilled subjects, whereas a similar relationship was established with REM density in less skilled subjects,128 in line with the proposal that motor skills tasks involving REM and stage 2 sleep might depend on two separate, but overlapping, neural systems.28 This interpretation may be consistent with neuroimaging data that have established a relationship between posttraining REM sleep activity and the consolidation of higher-order perceptual–motor cognitive skills. Indeed, subcortical and neocortical areas already activated during practice on a probabilistic sequence-learning task140 (i.e., a paradigm of implicit sequence learning) were reactivated during posttraining REM sleep in subjects previously trained to the task.56,57,61 It was further demonstrated that these reactivations were not merely activity dependent but occurred specifically because a rules-based sequence was implicitly learned during prior practice,57 supporting the hypothesis that REM sleep is deeply involved in the reprocessing and optimization of the high-order information contained in the material to be learned, as opposed to its motor component alone. Moreover, it was found in a 40-hour constant routine protocol in which subjects were allowed 75 minutes of sleep every 150 minutes that sequence learning improved after naps, and most especially after naps that followed the circadian peak of REM sleep and in which REM sleep was present.141 Nonetheless, further studies using sequence-learning tasks have raised several issues, and some of these remain to be solved. It has been claimed that sleep is beneficial for sequence learning only when acquisition of the sequential regularities practiced during the task was explicit, with time alone being sufficient for the consolidation of implicitly acquired sequences.23,142 These results appear to contradict the findings of REM-sleep dependency for high-order probabilistic sequence learning, in which learning was undoubtedly implicit.57,140,141 However, one overlooked difference between these studies and those claiming a sleep dependency exclusively for explicit sequential material is that the latter have used deterministic, repeated sequences, whereas the probabilistic sequences used in the former studies are much more ambiguous. It is therefore possible that sleep (and especially REM sleep) mostly supports the consolidation of implicitly acquired complex relationships. This interpretation may be in line with the proposal that different aspects of a procedural memory are processed separately during consolidation, such as the movement sequence in itself (e.g., a repeated, deterministic sequence) improves over daytime wakefulness periods independently of sleep, whereas its goal (e.g., the complex, abstract rules for item succession in a probabilistic sequence) improves after a night of sleep.129 How and whether offline processes of memory consolidation do actually benefit from posttraining sleep may also be a function of the circadian moment of the day when the material is acquired,127 as well as the nature of the complex interactions between declarative and procedural memory systems.22 The complexity of these interactions is further illustrated by the demonstration that learning-related 8/24/2010 7:23:51 PM L 342 PART I / Section 4 • Physiology in Sleep cerebral responses in cerebral structures linked to procedural (i.e., striatum) and declarative (i.e., hippocampus) memory systems are both linearly related to an overnight gain in performance in an implicit oculomotor sequencelearning task.143 Sleep and Priming Perceptual priming refers to the facilitation or bias in the processing of a stimulus as a function of a recent encounter with that stimulus.144 The few studies that have investigated a role for sleep in consolidating the memory representations subtending priming16,145,146 or priming-like147,148 effects have yielded discrepant results. Although studies have found that intervening deprivation of sleep, and especially REM sleep, alters priming effects in word-stem completion16 as well as in face processing,145 and enhances reactivity for emotional pictures,147 another study (using better controlled tachistoscopic identification of drawings) failed to disclose sleep-dependent effects.146 A variant of priming is the “mere exposure effect,” obtained when incidental exposure to initially novel stimuli (e.g., nonsense words, line drawings, ideograms, faces, novel three-dimensional objects) increases the likelihood that they will be favored over nonpresented items later on during a preference judgment.144 Using this task to investigate the effects of time, postexposure sleep, and cerebral lateralization, it was found that although detrimental in both hemispheres, total sleep deprivation did not affect performances to the same extent, suggesting interhemispheric differences in sleep-dependent processes of memory consolidation.148 Indeed, sleep deprivation abolished all memory effects only in the right hemisphere.148 Interhemispheric differences in wake- and sleep-dependent memory consolidation processes should therefore be investigated in more detail in the future. SLEEP-DEPENDENT MECHANISMS OF BRAIN PLASTICITY AND MEMORY CONSOLIDATION In this section, we provide a rapid overview of specific mechanisms viewed as particularly important to support sleep-stage–related processes of brain plasticity and memory consolidation: PGO waves, hippocampal rhythms, and sleep spindles. L PGO Waves Ponto-geniculo-occipital waves are prominent phasic bioelectrical potentials, closely related to rapid eye movements, occurring in isolation or in bursts during the transition from NREM to REM sleep or during REM sleep itself. PGO waves are a fundamental process of REM sleep in animals, playing a significant role in central nervous system maturation.34 Intracerebral recordings in epileptic patients,149 and noninvasive PET,150 fMRI,151 and magnetoencephalography152 scanning in healthy volunteers, indicate that the rapid eye movements observed during REM sleep are generated by mechanisms similar or identical to PGO waves in animals. Most importantly, animal data have suggested that PGO activity during REM sleep is associated with learning and memory consolidation,34 suggesting that activation of this generator during Kryger_6453_Ch 29_main.indd 342 REM sleep may represent one of the natural physiologic processes of memory, possibly through the synchronization of fast oscillations that would convey experiencedependent information in thalamocortical and intracortical circuits.153 Despite evidence from animal studies, a direct demonstration of the association between PGO activity and memory consolidation during REM sleep in humans has yet to be done. Nonetheless, the hypothesis is supported by studies showing an increase in the density of rapid eye movements during REM sleep after procedural learning40,154 and intensive learning periods,39 or a correlation between retention levels after learning Morse code and the frequency of rapid eye movements during posttraining REM sleep.37 Also, presenting sounds in the background while learning a complex logic task in the awake state enhanced next-morning performance when the same sounds were presented again during REM sleep. Most interestingly, however, enhancement was found only when sounds were coincident with the bursts of posttraining rapid eye movements that reflect PGO activity,74 further suggesting the association of REM sleep with memory consolidation processes. Also, it has been proposed that during human phasic REM sleep, propagation of PGO activity in the parahippocampal or hippocampal area is linked with verbal learning performance and mnemonic retention values.155 Hippocampal Rhythms The theta rhythm (i.e., regular sinusoidal oscillations in the frequency range of 4 to 7 Hz recorded in the hippocampal EEG) is a prominent signature of REM sleep in mammals, including humans.156 Theta represents the online state of the hippocampus, believed to be critical for temporal coding or decoding of active neuronal ensembles and the modification of synaptic weights.156 Additionally, population synchrony of pyramidal cells is maximal during quiet wakefulness and SWS associated with sharp waves (i.e., sharp waves of SWS are the consequence of synchronous discharge of bursting CA3 pyramidal neurons) and fast ripples (140 to 200 Hz). Sharp waves and ripples during SWS constitute good candidates to induce neuronal plasticity.157 Thus, the alternation between both REM sleep/active-awake theta activity and SWS/quiet-wakefulness sharp waves and ripples could contribute to brain plasticity. According to the two-stage model of memory formation,157 neocortical information activates the entorhinal input, which will cause synaptic changes to occur in the hippocampal CA3 system during learning associated with active waking and REM sleep theta rhythmic activity in the hippocampus. In the subsequent nontheta state (i.e., SWS, but possibly also quiet wakefulness), previously activated neurons are reactivated during sharp wave bursts, and the memory representation transiently stored in the CA3 region can be transferred to neocortical targets for the long term. Accordingly, human brain imaging studies have demonstrated after spatial navigation in a virtual town the experience-dependent reactivation of hippocampal activity during SWS, but not during REM sleep.58 Similarly, an odor-cued activation in hippocampus-related memory areas was observed during SWS,77 eventually leading to 8/24/2010 7:23:51 PM overnight performance improvement. These studies also found long-term transfer of hippocampal memories toward neocortical stores,31,83 an effect disturbed by sleep deprivation on the posttraining night.31 In parallel, neuroimaging data have suggested the offline persistence of memory-related cerebral activity during active wakefulness and its dynamic evolution in the hippocampus.21 Although this model is well supported by the these data and may account for the offline processing of declarative material, the fact that reactivations have been observed during both posttraining REM sleep56,57 and wakefulness21 after procedural, nonhippocampal learning suggests that other routes for consolidation exist, which should likewise be investigated. Sleep Spindles and Slow Waves Traditionally, the sleep spindle has been defined as the presence of rhythmic 12- to 14-Hz activity lasting a minimum of 0.5 seconds and displaying an increasing, then decreasing, amplitude envelope. This definition has expanded to 12 to 16 Hz and includes both slow (11.5- to 14-Hz) and fast (14- to 16-Hz) spindles, which may reflect two separate spindle generators with different brain topographies.158,159 Although spindles occur most frequently in stage 2, they also appear to a lesser extent in delta sleep (stages 3 and 4). A negative reciprocal relationship between SWA and spindle occurrence seems to exist in NREM sleep.158 Spindle mechanisms have been studied in the cat.160,161 They are considered to result from intrinsic properties and from the connectivity patterns of the thalamic neurons. Spindle generation seems an ideal mechanism for neural plasticity.96 Therefore, spindles may play an important role in the processes of memory consolidation during sleep. Accordingly, several studies have reported links between the consolidation of verbal declarative memory and increases in spindle density during the nocturnal and diurnal sleep that follows learning.41,42,44,49 Verbal memory association with spindle density increased in the left frontocentral scalp location at night, whereas memory for faces did not elicit this effect.49 Similarly, postlearning increases are observed during daytime napping in low-frequency spectral power (11.25 to 13.75 Hz), particularly in the left frontal scalp region. Additionally, these increases are positively correlated with learning performance in the difficult word-association task, but not in the easy word-association task or control condition.42 Similarly for procedural memory, posttraining stage 2 sleep deprivation impaired memory for a perceptual–motor task,27 and the amount of stage 2 correlated with learning progress on the fingertapping task.109,111 Also, intensive training on perceptual– motor learning tasks results in marked increases in number and density of spindles during subsequent stage 2 sleep47 as well as an increase in average spindle duration.51 Posttraining increases in slow sigma power (12 to 14 Hz) have been observed in frontal and occipital regions with no changes in high-frequency sigma.51 Napping studies using the same task provided similar results: subjects who regularly napped showed positive correlations between postnap performance and stage 2 spindle density.162 In this case, low-frequency spindles (12 to 14 Hz) were correlated with performance at frontal sites, whereas high-frequency Kryger_6453_Ch 29_main.indd 343 CHAPTER 29 • Memory Processing in Relation to Sleep 343 spindle activity (14 to 16 Hz) was correlated with performance at central and parietal sites. Moreover, subjects who did not nap on a regular basis did not benefit from an experimental nap in the study design.162 In another study using a longer (60- to 90-minute) nap after motor performance for the finger-tapping task, it was found that those subjects with the most significant increases in motor performance also had the largest increases in stage 2 sleep, with a significant correlation between spindle density and postnap performance that was confined to the learning hemisphere.46 Finally, a marked increase in stage 2 spindle densities was observed after acquisition of the finger-tapping task, but not after a control motor task, indicating that the changes were not the result of general motor activity.110 That spindles have been related to consolidation for both declarative and nondeclarative memories indicates their prominent role in sleep-dependent memory processes. Still, it should be noticed that although stage 2 has been the predominant stage of sleep involved, closer examination showed that REM sleep appeared to be more important for some participants after perceptual–motor learning.128 To explain this, it has been proposed that there are two independent neural systems for sleep-dependent memory consolidation, one involved with stage 2 sleep, the other with REM sleep. In this respect, subjects who report the perceptual–motor task as being a novel experience show an increase in density of rapid eye movements during postacquisition REM sleep, but no changes in stage 2 sleep parameters. On the other hand, those individuals who find the task to be similar to others they have already experienced in their lives (as shown by reasonably good performance on the first few trials of the task) will show an increase in spindle density during stage 2 sleep but no changes in REM sleep. These latter subjects are considered to be refining an existing motor program rather than learning a new one.28 In addition, spindle oscillations are grouped and regulated by slow waves163 that are thought to be important for memory consolidation, as discussed earlier. Indeed, experience-dependent regional increases in delta activity have been shown during NREM sleep,63 suggesting local homeostatic mechanisms for memory consolidation.62 Furthermore, coherence was found to increase after learning in the depolarizing phase of the slow oscillations below the 1-Hz frequency.163 On the other hand, transcranial direct current stimulation that may contribute to modulation of cortical excitability was found to improve the overnight retention of declarative memories when applied during NREM sleep at a slow rhythm whose frequency (less than 1 Hz) approximates these slow oscillations,75 further suggesting a facilitatory role of slow oscillatory EEG activity in neuronal plasticity and the ongoing transformations and consolidation of memory traces. Conclusions Although their results are at times elusive, studies supporting the proposal that sleep is an integral component in the offline processes that subtend memory consolidation have now substantially flourished. Still, when compared with other domains of cognition, the field remains 8/24/2010 7:23:51 PM L 344 PART I / Section 4 • Physiology in Sleep underdeveloped. There is an urgent need for replication and validation of studies to confirm or disprove a series of hypotheses regarding which memories can benefit from sleep, and in which circumstances this can occur. Furthermore, the mechanisms that support these processes remain to be fully elucidated and understood. Most important, we need to understand how sleep disorders and the numerous pathologies accompanied by sleep disturbances affect cognitive processes, especially learning and memory, and to understand the extent to which sleep manipulation helps or speeds up resolution of these pathologies. This is an exciting area of research for sleep specialists, neuroscientists, and cognitive psychologists, who should join forces to help patients suffering from sleep-related afflictions. ❖ Clinical Pearls In the long term, patients with inadequate REM sleep may be expected to experience more difficulty learning novel cognitive procedures than same-age individuals with healthy sleep. Patients exhibiting little or impaired slow-wave sleep may be impaired in declarative learning (e.g., memorizing large amounts of factual material). Those with specific stage 2 sleep disturbances can be expected to have trouble refining and performing reasonably simple motor skill tasks. Patients with poor sleep quality or pathologies affecting all sleep stages can be expected to have deteriorated long-term performance with all types of memory. Sleep is only a part of memory consolidation processes, however, so these deficits may manifest in a subtle manner and may, to a certain extent, be compensated for by alternative consolidation strategies. In-depth clinical investigation of memory problems should always be done by a trained neuropsychologist. REFERENCES L 1. Saint-Denys HD. Les rêves et les moyens de les diriger. Paris: Editions d’Aujourd’hui; 1977. 2. Rauchs G, Desgranges B, Foret J, Eustache F, et al. The relationships between memory systems and sleep stages. J Sleep Res 2005;14:123-140. 3. Smith C. Sleep states, memory processes and synaptic plasticity. Behav Brain Res 1996;78:49-56. 4. Maquet P, Smith C, Stickgold R. Sleep and brain plasticity. Oxford: Oxford University Press; 2003. 5. Squire LR. Memory systems of the brain: a brief history and current perspective. Neurobiol Learn Mem 2004;82:171-177. 6. Peigneux P, Laureys S, Delbeuck X, Maquet P, et al. Sleeping brain, learning brain. The role of sleep for memory systems. Neuroreport 2001;12:A111-A124. 7. Smith C. Sleep states and memory processes in humans: procedural versus declarative memory systems. Sleep Med Rev 2001;5: 491-506. 8. McClelland JL, McNaughton BL, O’Reilly RC. Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. Psychol Rev 1995;102:419-457. 9. Bontempi B, Laurent-Demir C, Destrade C, Jaffard R, et al. Timedependent reorganization of brain circuitry underlying long-term memory storage. Nature 1999;400:671-675. Kryger_6453_Ch 29_main.indd 344 10. Karni A, Meyer G, ReyHipolito C, Adams MN, et al. The acquisition of skilled motor performance: fast and slow experiencedriven changes in primary motor cortex. PNAS USA 1998;95: 861-868. 11. Wixted JT. The psychology and neuroscience of forgetting. Annu Rev Psychol 2004;55:235-269. 12. McGaugh JL. Time-dependent processes in memory storage. Science 1966;153:1351-1358. 13. Kolb B, Whishaw IQ. Brain plasticity and behavior. Annu Rev Psychol 1998;49:43-64. 14. Gaarder K. A conceptual model of sleep. Arch Gen Psychiatry 1966;14:253-260. 15. Plihal W, Born J. Effects of early and late nocturnal sleep on declarative and procedural memory. J Cogn Neurosci 1997;9: 534-547. 16. Plihal W, Born J. Effects of early and late nocturnal sleep on priming and spatial memory. Psychophysiology 1999;36:571582. 17. Giuditta A, Ambrosini MV, Montagnese P, Montagnese P, et al. The sequential hypothesis of the function of sleep. Behav Brain Res 1995;69:157-166. 18. Scrima L. Isolated REM sleep facilitates recall of complex associative information. Psychophysiology 1982;19:252-259. 19. Ficca G, Lombardo P, Rossi L, Salzarulo P, et al. Morning recall of verbal material depends on prior sleep organization. Behav Brain Res 2000;112:159-163. 20. Stickgold R, Whidbee D, Schirmer B, Patel V, et al. Visual discrimination task improvement: a multi-step process occurring during sleep. J Cogn Neurosci 2000;12:246-254. 21. Peigneux P, Orban P, Balteau E, Degueldre C, et al. Offline persistence of memory-related cerebral activity during active wakefulness. PLoS Biol 2006;4:e100. 22. Brown RM, Robertson EM. Off-line processing: reciprocal interactions between declarative and procedural memories. J Neurosci 2007;27:10468-10475. 23. Robertson EM, Pascual-Leone A, Press DZ. Awareness modifies the skill-learning benefits of sleep. Curr Biol 2004;14:208-212. 24. Jenkins J, Dallenbach K. Obliviscence during sleep and waking. Am J Psychol 1924;35:605-612. 25. Smith C. Sleep states and learning: a review of the animal literature. Neurosci Biobehav Rev 1985;9:157-168. 26. Ekstrand BR. Effect of sleep on memory. J Exp Psychol 1967; 75:64-72. 27. Smith C, MacNeill C. Impaired motor memory for a pursuit rotor task following Stage 2 sleep loss in college students. J Sleep Res 1994;3:206-213. 28. Smith C, Aubrey J, Peters K. Different roles for REM and stage 2 sleep in motor learning: a proposed model. Psychol Belg 2004;44: 79-102. 29. Maquet P, Schwartz S, Passingham R, Frith C. Sleep-related consolidation of a visuomotor skill: brain mechanisms as assessed by functional magnetic resonance imaging. J Neurosci 2003;23: 1432-1440. 30. Rauchs G, Orban P, Schmidt C, Albouy G, et al. Sleep modulates the neural substrates of both spatial and contextual memory consolidation. PLoS ONE 2008;3:e2949. 31. Gais S, Albouy G, Boly M, Dang-Vu TT, et al. Sleep transforms the cerebral trace of declarative memories. PNAS USA 2007; 104:18778-18783. 32. Orban P, Rauchs G, Balteau E, Degueldre C, et al. Sleep after spatial learning promotes covert reorganization of brain activity. PNAS USA 2006;103:7124-7129. 33. Hennevin E, Huetz C, Edeline JM. Neural representations during sleep: from sensory processing to memory traces. Neurobiol Learn Mem 2007;87:416-440. 34. Datta S, Patterson EH. Activation of phasic pontine wave (P-wave): A mechanism of learning and memory processing. In: Maquet P, Smith C, Stickgold R, editors. Sleep and brain plasticity. Oxford, UK: Oxford University Press; 2003. p. 135-156. 35. Buchegger J, Meier-Koll A. Motor learning and ultradian sleep cycle: an electroencephalographic study of trampoliners. Percept Mot Skills 1988;67:635-645. 36. de Koninck J, Lorrain D, Christ G, Proulx G, et al. Intensive language learning and increases in rapid eye movement sleep: evidence of a performance factor. Int J Psychophysiol 1989;8:43-47. 8/24/2010 7:23:51 PM CHAPTER 29 • Memory Processing in Relation to Sleep 345 37. Mandai O, Guerrien A, Sockeel P, Dujardin K, et al. REM sleep modifications following a Morse code learning session in humans. Physiol Behav 1989;46:639-642. 38. Meier-Koll A, Bussman B, Schmidt C, Neuschwander D. Walking through a maze alters the architecture of sleep. Percept Mot Skills 1999;88:1141-1159. 39. Smith C, Lapp L. Increases in number of REMS and REM density in humans following an intensive learning period. Sleep 1991; 14:325-330. 40. Smith CT, Nixon MR, Nader RS. Posttraining increases in REM sleep intensity implicate REM sleep in memory processing and provide a biological marker of learning potential. Learn Mem 2004;11:714-719. 41. Gais S, Molle M, Helms K, Born J. Learning-dependent increases in sleep spindle density. J Neurosci 2002;22:6830-6834. 42. Schmidt C, Peigneux P, Muto V, Schenkel M, et al. Encoding difficulty promotes postlearning changes in sleep spindle activity during napping. J Neurosci 2006;26:8976-8982. 43. Tamaki M, Matsuoka T, Nittono H, Hori T. Fast sleep spindle (13-15 hz) activity correlates with sleep-dependent improvement in visuomotor performance. Sleep 2008;31:204-211. 44. Schabus M, Hoedlmoser K, Pecherstorfer T, Anderer P, et al. Interindividual sleep spindle differences and their relation to learning-related enhancements. Brain Res 2008;1191:127-135. 45. Peters KR, Ray L, Smith V, Smith C. Changes in the density of stage 2 sleep spindles following motor learning in young and older adults. J Sleep Res 2008;17:23-33. 46. Nishida M, Walker MP. Daytime naps, motor memory consolidation and regionally specific sleep spindles. PLoS ONE 2007;2:e341. 47. Fogel SM, Smith CT. Learning-dependent changes in sleep spindles and Stage 2 sleep. J Sleep Res 2006;15:250-255. 48. Clemens Z, Fabo D, Halasz P. Twenty-four hours retention of visuospatial memory correlates with the number of parietal sleep spindles. Neurosci Lett 2006;403:52-56. 49. Clemens Z, Fabo D, Halasz P. Overnight verbal memory retention correlates with the number of sleep spindles. Neuroscience 2005;132:529-535. 50. Schabus M, Gruber G, Parapatics S, Sauter C, et al. Sleep spindles and their significance for declarative memory consolidation. Sleep 2004;27:1479-1485. 51. Fogel SM, Smith CT, Cote KA. Dissociable learning-dependent changes in REM and non-REM sleep in declarative and procedural memory systems. Behav Brain Res 2007;180:48-61. 52. Mazzoni G, Gori S, Formicola G, Gneri C, et al. Word recall correlates with sleep cycles in elderly subjects. J Sleep Res 1999;8: 185-188. 53. Stickgold R, Malia A, Maguire D, Roddenberry D, et al. Replaying the game: hypnagogic images in normals and amnesics. Science 2000;290:350-353. 54. Corsi-Cabrera M, Becker J, Garcia L, Ibarra R, et al. Dream content after using visual inverting prisms. Percept Mot Skills 1986;63:415-423. 55. Nielsen TA, Kuiken D, Alain G, Stenstrom P, et al. Immediate and delayed incorporations of events into dreams: further replication and implications for dream function. J Sleep Res 2004;13: 327-336. 56. Maquet P, Laureys S, Peigneux P, Fuchs S, et al. Experiencedependent changes in cerebral activation during human REM sleep. Nature Neurosci 2000;3:831-836. 57. Peigneux P, Laureys S, Fuchs S, Destrebecqz A, et al. Learned material content and acquisition level modulate cerebral reactivation during posttraining rapid-eye-movements sleep. Neuroimage 2003;20:125-134. 58. Peigneux P, Laureys S, Fuchs S, Collette F, et al. Are spatial memories strengthened in the human hippocampus during slow wave sleep? Neuron 2004;44:535-545. 59. Dave AS, Margoliash D. Song replay during sleep and computational rules for sensorimotor vocal learning. Science 2000;290: 812-816. 60. Wilson MA, McNaughton BL. Reactivation of hippocampal ensemble memories during sleep. Science 1994;265:676-679. 61. Laureys S, Peigneux P, Phillips C, Fuchs S, et al. Experiencedependent changes in cerebral functional connectivity during human rapid eye movement sleep. Neuroscience 2001;105:521525. Kryger_6453_Ch 29_main.indd 345 62. Tononi G, Cirelli C. Sleep function and synaptic homeostasis. Sleep Med Rev 2006;10:49-62. 63. Huber R, Ghilardi MF, Massimini M, Tononi G. Local sleep and learning. Nature 2004;430:78-81. 64. Ikeda K, Morotomi T. Classical conditioning during human NREM sleep and response transfer to wakefulness. Sleep 1996; 19:72-74. 65. Wood JM, Bootzin RR, Kihlstrom JF, Schacter DL. Implicit and explicit memory for verbal information presented during sleep. Psychol Science 1992;3:236-239. 66. Bastuji H, Perrin F, Garcia-Larrea L. Semantic analysis of auditory input during sleep: studies with event-related potentials. Int J Psychophysiol 2002;46:243-255. 67. Atienza M, Cantero JL, Escera C. Auditory information processing during human sleep as revealed by event-related brain potentials. Clin Neurophysiol 2001;112:2031-2045. 68. Lavigne G, Brousseau M, Kato T, Mayer P, et al. Experimental pain perception remains equally active over all sleep stages. Pain 2004;110:646-655. 69. Takahara M, Nittono H, Hori T. Comparison of the event-related potentials between tonic and phasic periods of rapid eye movement sleep. Psychiatry Clin Neurosci 2002;56:257-258. 70. Wehrle R, Kaufmann C, Wetter TC, Holsboer F, et al. Functional microstates within human REM sleep: first evidence from fMRI of a thalamocortical network specific for phasic REM periods. Eur J Neurosci 2007;25:863-871. 71. Perrin F, Garcia-Larrea L, Mauguiere F, Bastuji H. A differential brain response to the subject’s own name persists during sleep. Clin Neurophysiol 1999;110:2153-2164. 72. Brualla J, Romero MF, Serrano M, Valdizan JR. Auditory eventrelated potentials to semantic priming during sleep. Electroencephalogr Clin Neurophysiol 1998;108:283-290. 73. Guerrien A, Dujardin K, Mandai O, Sockeel P, et al. Enhancement of memory by auditory stimulation during postlearning REM sleep in humans. Physiol Behav 1989;45:947-950. 74. Smith C, Weeden K. Post training REMs coincident auditory stimulation enhances memory in humans. Psych J Univ Ottawa 1990;15:85-90. 75. Marshall L, Helgadottir H, Molle M, Born J. Boosting slow oscillations during sleep potentiates memory. Nature 2006;444: 610-613. 76. Marshall L, Molle M, Hallschmid M, Born J, et al. Transcranial direct current stimulation during sleep improves declarative memory. J Neurosci 2004;24:9985-9992. 77. Rasch B, Buchel C, Gais S, Born J. Odor cues during slow-wave sleep prompt declarative memory consolidation. Science 2007;315: 1426-1429. 78. Plihal W, Born J. Memory consolidation in human sleep depends on inhibition of glucocorticoid release. Neuroreport 1999;10: 2741-2748. 79. Gais S, Born J. Low acetylcholine during slow-wave sleep is critical for declarative memory consolidation. PNAS USA 2004;101: 2140-2144. 80. Wagner U, Degirmenci M, Drosopoulos S, Perras B, et al. Effects of cortisol suppression on sleep-associated consolidation of neutral and emotional memory. Biol Psychiatry 2005;58:885-893. 81. Rasch BH, Born J, Gais S. Combined blockade of cholinergic receptors shifts the brain from stimulus encoding to memory consolidation. J Cogn Neurosci 2006;18:793-802. 82. Stickgold R, Scott L, Rittenhouse C, Hobson JA. Sleep-induced changes in associative memory. J Cogn Neurosci 1999;11:182193. 83. Takashima A, Petersson KM, Rutters F, Tendolkar I, et al. Declarative memory consolidation in humans: a prospective functional magnetic resonance imaging study. PNAS USA 2006;103:756761. 84. Ellenbogen JM, Hulbert JC, Stickgold R, Dinges DF, et al. Interfering with theories of sleep and memory: sleep, declarative memory, and associative interference. Curr Biol 2006;16:1290-1294. 85. Tucker MA, Hirota Y, Wamsley EJ, Lau H, et al. A daytime nap containing solely non-REM sleep enhances declarative but not procedural memory. Neurobiol Learn Mem 2006;86:241-247. 86. Backhaus J, Born J, Hoeckesfeld R, Fokuhl S, et al. Midlife decline in declarative memory consolidation is correlated with a decline in slow wave sleep. Learn Mem 2007;14:336-341. 8/24/2010 7:23:51 PM L 346 PART I / Section 4 • Physiology in Sleep L 87. Backhaus J, Hoeckesfeld R, Born J, Hohagen F, et al. Immediate as well as delayed post learning sleep but not wakefulness enhances declarative memory consolidation in children. Neurobiol Learn Mem 2008;89:76-80. 88. Tucker MA, Fishbein W. Enhancement of declarative memory performance following a daytime nap is contingent on strength of initial task acquisition. Sleep 2008;31:197-203. 89. Rauchs G, Bertran F, Guillery-Girard B, Desgranges B, et al. Consolidation of strictly episodic memories mainly requires rapid eye movement sleep. Sleep 2004;27:395-401. 90. Wagner U, Gais S, Born J. Emotional memory formation is enhanced across sleep intervals with high amounts of rapid eye movement sleep. Learn Mem 2001;8:112-119. 91. Talamini LM, Nieuwenhuis IL, Takashima A, Jensen O. Sleep directly following learning benefits consolidation of spatial associative memory. Learn Mem 2008;15:233-237. 92. Ferrara M, Iaria G, Tempesta D, Curcio G, et al. Sleep to find your way: the role of sleep in the consolidation of memory for navigation in humans. Hippocampus 2008;18:844-851. 93. Ferrara M, Iaria G, De Gennaro L, Guariglia C, et al. The role of sleep in the consolidation of route learning in humans: a behavioural study. Brain Res Bull 2006;71:4-9. 94. Goder R, Boigs M, Braun S, Friege L, et al. Impairment of visuospatial memory is associated with decreased slow wave sleep in schizophrenia. J Psychiatr Res 2004;38:591-599. 95. Goder R, Fritzer G, Gottwald B, Lippmann B, et al. Effects of olanzapine on slow wave sleep, sleep spindles and sleep-related memory consolidation in schizophrenia. Pharmacopsychiatry 2008; 41:92-99. 96. Destexhe A, Sejnowski TJ. Thalamocortical assemblies: how ion channels, single neurons, and large-scale networks organize sleep oscillations. New York: Oxford University Press; 2001. 97. Schabus M, Hodlmoser K, Gruber G, Sauter C, et al. Sleep spindlerelated activity in the human EEG and its relation to general cognitive and learning abilities. Eur J Neurosci 2006;23:17381746. 98. Ferini-Strambi L, Ortelli P, Castronovo V, Cappa S. Increased periodic arousal fluctuations during non-REM sleep are associated to superior memory. Brain Res Bull 2004;63:439-442. 99. Rauchs G, Schabus M, Parapatics S, Bertran F, et al. Is there a link between sleep changes and memory in Alzheimer’s disease? Neuroreport 2008;19:1159-1162. 100. Goder R, Scharffetter F, Aldenhoff JB, Fritzer G. Visual declarative memory is associated with non-rapid eye movement sleep and sleep cycles in patients with chronic non-restorative sleep. Sleep Med 2007;8:503-508. 101. Empson JA, Clarke PR. Rapid eye movements and remembering. Nature 1970;227:287-288. 102. Tilley AJ. Retention over a period of REM or non-REM sleep. Brit J Psychol 1981;72:241-248. 103. Drosopoulos S, Wagner U, Born J. Sleep enhances explicit recollection in recognition memory. Learn Mem 2005;12:44-51. 104. Drosopoulos S, Windau E, Wagner U, Born J. Sleep enforces the temporal order in memory. PLoS ONE 2007;2:e376. 105. Hu P, Stylos-Allan M, Walker MP. Sleep facilitates consolidation of emotional declarative memory. Psychol Sci 2006;17:891-898. 106. Sterpenich V, Albouy G, Boly M, Vandewalle G, et al. Sleep-related hippocampo-cortical interplay during emotional memory recollection. PLoS Biol 2007;5:e282. 107. Atienza M, Cantero JL. Modulatory effects of emotion and sleep on recollection and familiarity. J Sleep Res 2008; 108. Payne JD, Stickgold R, Swanberg K, Kensinger EA. Sleep preferentially enhances memory for emotional components of scenes. Psychol Sci 2008;19:781-788. 109. Walker MP, Brakefield T, Hobson AJ, Stickgold R. Dissociable stages of human memory consolidation and reconsolidation. Nature 2003;425:616-620. 110. Morin A, Doyon J, Dostie V, Barakat M, et al. Motor sequence learning increases sleep spindles and fast frequencies in post-training sleep. Sleep 2008;31:1149-1156. 111. Walker MP, Brakefield T, Morgan A, Hobson JA, et al. Practice with sleep makes perfect: sleep-dependent motor skill learning. Neuron 2002;35:205-211. 112. Korman M, Raz N, Flash T, Karni A. Multiple shifts in the representation of a motor sequence during the acquisition of skilled performance. PNAS USA 2003;100:12492-12497. Kryger_6453_Ch 29_main.indd 346 113. Kuriyama K, Stickgold R, Walker MP. Sleep-dependent learning and motor-skill complexity. Learn Mem 2004;11:705-713. 114. Korman M, Doyon J, Doljansky J, Carrier J, et al. Daytime sleep condenses the time course of motor memory consolidation. Nat Neurosci 2007;10:1206-1213. 115. Buchegger J, Fritsch R, Meier-Koll A, Riehle H. Does trampolining and anaerobic physical fitness affect sleep? Percept Mot Skills 1991;73:243-252. 116. Gais S, Plihal W, Wagner U, Born J. Early sleep triggers memory for early visual discrimination skills. Nature Neurosci 2000;3: 1335-1339. 117. Fenn KM, Nusbaum HC, Margoliash D. Consolidation during sleep of perceptual learning of spoken language. Nature 2003;425: 614-616. 118. Gaab N, Paetzold M, Becker M, Walker MP, et al. The influence of sleep on auditory learning: a behavioral study. Neuroreport 2004;15:731-734. 119. Matarazzo L, Franko E, Maquet P, Vogels R. Offline processing of memories induced by perceptual visual learning during subsequent wakefulness and sleep: a behavioral study. J Vis 2008;8: 71-79. 120. Gais S, Rasch B, Wagner U, Born J. Visual-procedural memory consolidation during sleep blocked by glutamatergic receptor antagonists. J Neurosci 2008;28:5513-5518. 121. Walker MP, Stickgold R, Jolesz FA, Yoo S-S. The functional anatomy of sleep-dependent visual skill learning. Cereb Cortex 2005;15:1666-1675. 122. Mednick S, Nakayama K, Stickgold R. Sleep-dependent learning: a nap is as good as a night. Nat Neurosci 2003;6:697-698. 123. Mednick SC, Nakayama K, Cantero JL, Atienza M, et al. The restorative effect of naps on perceptual deterioration. Nat Neurosci 2002;5:677-681. 124. Karni A, Tanne D, Rubenstein S, Askenasy JJM, et al. Dependence on REM sleep of overnight improvement of a perceptual skill. Science 1994;265:679-682. 125. Backhaus J, Junghanns K. Daytime naps improve procedural motor memory. Sleep Med 2006;7:508-512. 126. Smith C, MacNeill C. Memory for motor task is impaired by stage 2 sleep loss. J Sleep Res 1992;21:139. 127. Cohen DA, Robertson EM. Motor sequence consolidation: constrained by critical time windows or competing components. Exp Brain Res 2007;177:440-446. 128. Peters KR, Smith V, Smith CT. Changes in sleep architecture following motor learning depend on initial skill level. J Cogn Neurosci 2007;19:817-829. 129. Cohen DA, Pascual-Leone A, Press DZ, Robertson EM. Off-line learning of motor skill memory: a double dissociation of goal and movement. PNAS USA 2005;102:18237-18241. 130. Gomez Beldarrain M, Astorgano AG, Gonzalez AB, GarciaMonco JC. Sleep improves sequential motor learning and performance in patients with prefrontal lobe lesions. Clin Neurol Neurosurg 2008;110:245-252. 131. Siengsukon CF, Boyd LA. Sleep enhances implicit motor skill learning in individuals poststroke. Top Stroke Rehabil 2008;15: 1-12. 132. Marinelli L, Crupi D, Di Rocco A, Bove M, et al. Learning and consolidation of visuo-motor adaptation in Parkinson’s disease. Parkinsonism Relat Disord 2009;15:6-11. 133. Karni A, Sagi D. Where practice makes perfect in texture discrimination: evidence for primary visual cortex plasticity. PNAS USA 1991;88:4966-4970. 134. Atienza M, Cantero JL, Stickgold R. Posttraining sleep enhances automaticity in perceptual discrimination. J Cogn Neurosci 2004; 16:53-64. 135. Gottselig JM, Hofer-Tinguely G, Borbely AA, Regel SJ, et al. Sleep and rest facilitate auditory learning. Neuroscience 2004;127: 557-561. 136. Roth DA, Kishon-Rabin L, Hildesheimer M, Karni A, et al. A latent consolidation phase in auditory identification learning: time in the awake state is sufficient. Learn Mem 2005;12:159164. 137. Dumay N, Gaskell MG. Sleep-associated changes in the mental representation of spoken words. Psychol Sci 2007;18:35-39. 138. Hotermans C, Peigneux P, Maertens de Noordhout A, Moonen G, et al. Early boost and slow consolidation in motor skill learning. Learn Mem 2006;13:580-583. 8/24/2010 7:23:51 PM 139. Fischer S, Hallschmid M, Elsner AL, Born J. Sleep forms memory for finger skills. PNAS USA 2002;99:11987-11991. 140. Peigneux P, Maquet P, Meulemans T, Born J. Striatum forever despite sequence learning variability: a random effect analysis of PET data. Hum Brain Mapp 2000;10:179-194. 141. Cajochen C, Knoblauch V, Wirz-Justice A, Krauchi K, et al. Circadian modulation of sequence learning under high and low sleep pressure conditions. Behav Brain Res 2004;151:167-176. 142. Spencer RM, Sunm M, Ivry RB. Sleep-dependent consolidation of contextual learning. Curr Biol 2006;16:1001-1005. 143. Albouy G, Sterpenich V, Balteau E, Vandewalle G, et al. Both the hippocampus and striatum are involved in consolidation of motor sequence memory. Neuron 2008;58:261-272. 144. Butler LT, Berry DC. Understanding the relationship between repetition priming and mere exposure. Br J Psychol 2004;95: 467-487. 145. Wagner U, Hallschmid M, Verleger R, Born J. Signs of REM sleep dependent enhancement of implicit face memory: a repetition priming study. Biol Psychol 2003;62:197-210. 146. Rauchs G, Lebreton K, Bertran F, Pelevin A, et al. Effects of partial sleep deprivation on within-format and cross-format priming. Sleep 2006;29:58-68. 147. Wagner U, Fischer S, Born J. Changes in emotional responses to aversive pictures across periods rich in slow-wave sleep versus rapid eye movement sleep. Psychosom Med 2002;64:627-634. 148. Peigneux P, Schmitz R, Willems S. Cerebral asymmetries in sleepdependent processes of memory consolidation. Learn Mem 2007; 14:400-406. 149. Salzarulo P, Lairy GC, Bancaud J, Munari C. Direct depth recording of the striate cortex during REM sleep in man: are there PGO potentials? EEG Clin Neurophysiol 1975;38:199-202. 150. Peigneux P, Laureys S, Fuchs S, Delbeuck X, et al. Generation of rapid eye movements during paradoxical sleep in humans. Neuroimage 2001;14:701-708. 151. Wehrle R, Czisch M, Kaufmann C, Wetter TC, et al. Rapid eye movement-related brain activation in human sleep: a functional CHAPTER 29 • Memory Processing in Relation to Sleep 347 magnetic resonance imaging study. Neuroreport 2005;16:853857. 152. Ioannides AA, Corsi-Cabrera M, Fenwick PB, del Rio Portilla Y, et al. MEG tomography of human cortex and brainstem activity in waking and REM sleep saccades. Cereb Cortex 2004;14:56-72. 153. Amzica F, Steriade M. Progressive cortical synchronization of ponto-geniculo-occipital potentials during rapid eye movement. Neuroscience 1996;72:309-314. 154. Smith C. Changes in density of REM sleep following acquisition of cognitive procedural tasks in humans. Actas Fisiol 2001;7:27. 155. Bodizs R, Bekesy M, Szucs A, Barsi P, et al. Sleep-dependent hippocampal slow activity correlates with waking memory performance in humans. Neurobiol Learn Mem 2002;78:441-457. 156. Buzsaki G. Theta oscillations in the hippocampus. Neuron 2002;33:325-340. 157. Buzsaki G, Carpi D, Csicsvari J, Dragoi G, et al. Maintenance and modification of firing rates and sequences in the hippocampus: does sleep play a role. In: Maquet P, Smith C, Stickgold R, editors. Sleep and brain plasticity. Oxford, UK: Oxford University Press; 2003. p. 247-269. 158. De Gennaro L, Ferrara M. Sleep spindles: an overview. Sleep Med Rev 2003;7:423-440. 159. Schabus M, Dang-Vu TT, Albouy G, Balteau E, et al. Hemodynamic cerebral correlates of sleep spindles during human non-rapid eye movement sleep. PNAS USA 2007;104:13164-13169. 160. Amzica F, Steriade M. Integration of low-frequency sleep oscillations in corticothalamic networks. Acta Neurobiol Exp 2000;60: 229-245. 161. Steriade M. Corticothalamic resonance, states of vigilance and mentation. Neuroscience 2000;101:243-276. 162. Milner CE, Fogel SM, Cote KA. Habitual napping moderates motor performance improvements following a short daytime nap. Biol Psychol 2006;73:141-146. 163. Molle M, Marshall L, Gais S, Born J. Learning increases human electroencephalographic coherence during subsequent slow sleep oscillations. Proc Natl Acad Sci U S A 2004;101:13963-13968. L Kryger_6453_Ch 29_main.indd 347 8/24/2010 7:23:51 PM