Sleep-dependent Processes Research Articles

Clock-Sleep Communication.

Rhythmicity is a characteristic feature of the inanimate universe. The organization of biological rhythms in time is an adaptation to the cyclical environmental changes brought on by the earth's rotation on its axis and around the sun. Circadian (L. Circa = "around or approximately"; diem = "a day") rhythms are biological responses to the geophysical light/dark (LD) cycle in which an organism adjusts to alterations in its internal physiology or external environment as a function of the time of day. Sleep has been considered a biological rhythm. Normal human sleep, an essential physiologic process, comprises two distinct phases: non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. A mature adult human's sleep/wake cycle displays a circadian rhythm with a ~24-hour cycle. According to the two-process model of sleep regulation, the human sleep/wake cycle is orchestrated by circadian and homeostatic processes. Sleep homeostasis (a sleep-dependent process) and circadian rhythm (a sleep-independent process) are two biological processes controlling the sleep/wake cycle. There are also ultradian (< 24-hour) rhythms, including the NREM-REM sleep cycle, which has been extensively studied. The clock and sleep genes both influence sleep. In this overview, we have reviewed the circadian genes and their role in regulating sleep. Besides, the gene expression and biological pathways associated with sleep and circadian rhythm-associated diseases also have been highlighted.

The GABAA receptor modulator zolpidem augments hippocampal-prefrontal coupling during non-REM sleep

Benzodiazepines and ‘Z-drugs’ (including zolpidem and zopiclone) are GABAA receptor (GABAAR) positive modulators commonly prescribed as hypnotics to treat insomnia and/or anxiety. However, alongside sedation, augmenting GABAAR function may also alter coordinated neuronal activity during sleep, thereby influencing sleep-dependent processes including memory consolidation. We used simultaneous recordings of neural population activity from the medial prelimbic cortex (PrL) and CA1 of the dorsal hippocampus (dCA1) of naturally sleeping rats to detail the effects of zolpidem on network activity during the cardinal oscillations of non-REM sleep. For comparison, we also characterized the effects of diazepam and 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP/gaboxadol), which acts predominantly at extra-synaptic GABAARs. Zolpidem and THIP significantly increased the amplitudes of slow-waves, which were attenuated by diazepam. Zolpidem increased hippocampal ripple density whereas diazepam decreased both ripple density and intrinsic frequency. While none of the drugs affected thalamocortical spindles in isolation, zolpidem augmented the temporal coordination between slow-waves and spindles. At the cellular level, analyses of spiking activity from 523 PrL and 579 dCA1 neurons revealed that zolpidem significantly enhanced synchronized pauses in cortical firing during slow-wave down states, while increasing correlated activity within and between dCA1 and PrL populations. Of the drugs compared here, zolpidem was unique in augmenting coordinated activity within and between hippocampus and neocortex during non-REM sleep. Zolpidem’s enhancement of hippocampal-prefrontal coupling may reflect the cellular basis of its potential to modulate offline memory processing.

Delta Oscillations Coordinate Intracerebellar and Cerebello-Hippocampal Network Dynamics during Sleep.

During sleep, the widespread coordination of neuronal oscillations across both cortical and subcortical brain regions is thought to support various physiological functions. However, how sleep-related activity within the brain's largest sensorimotor structure, the cerebellum, is multiplexed with well-described sleep-related mechanisms in regions such as the hippocampus remains unknown. We therefore simultaneously recorded from the dorsal hippocampus and three distinct regions of the cerebellum (Crus I, lobule VI, and lobules II/III) in male mice during natural sleep. Local field potential (LFP) oscillations were found to be coordinated between these structures in a sleep stage-specific manner. During non-REM sleep, prominent δ frequency coherence was observed between lobule VI and hippocampus, whereas non-REM-associated hippocampal sharp-wave ripple activity evoked discrete LFP modulation in all recorded cerebellar regions, with the shortest latency effects in lobule VI. We also describe discrete phasic sharp potentials (PSPs), which synchronize across cerebellar regions and trigger sharp-wave ripple suppression. During REM, cerebellar δ phase significantly modulated hippocampal theta frequency, and this effect was greatest when PSPs were abundant. PSPs were phase-locked to cerebellar δ oscillation peak and hippocampal theta oscillation trough, respectively. Within all three cerebellar regions, prominent LFP oscillations were observed at both low (δ, <4 Hz) and very high frequencies (∼250 Hz) during non-REM and REM sleep. Intracerebellar cross-frequency analysis revealed that δ oscillations modulate those in the very high-frequency range. Together, these results reveal multiple candidate physiological mechanisms to support "offline," bidirectional interaction within distributed cerebello-hippocampal networks.SIGNIFICANCE STATEMENT Sleep is associated with widespread coordination of activity across a range of brain regions. However, little is known about how activity within the largest sensorimotor region of the brain, the cerebellum, is both intrinsically organized and links with higher-order structures, such as the hippocampus, during sleep. By making multisite local field potential recordings in naturally sleeping mice, we reveal and characterize multiple sleep stage-specific physiological mechanisms linking three distinct cerebellar regions with the hippocampus. Central to these physiological mechanisms is a prominent δ (<4 Hz) oscillation, which temporally coordinates both intracerebellar and cerebello-hippocampal network dynamics. Understanding this distributed network activity is important for gaining insight into cerebellar contributions to sleep-dependent processes, such as memory consolidation.

Abnormally abrupt transitions from sleep-to-wake in Huntington's disease sheep (Ovis aries) are revealed by automated analysis of sleep/wake transition dynamics.

Sleep disturbance is a common and disruptive symptom of neurodegenerative diseases such as Alzheimer's and Huntington's disease (HD). In HD patients, sleep fragmentation appears at an early stage of disease, although features of the earliest sleep abnormalities in presymptomatic HD are not fully established. Here we used novel automated analysis of quantitative electroencephalography to study transitions between wake and non-rapid eye movement sleep in a sheep model of presymptomatic HD. We found that while the number of transitions between sleep and wake were similar in normal and HD sheep, the dynamics of transitions from sleep-to-wake differed markedly between genotypes. Rather than the gradual changes in EEG power that occurs during transitioning from sleep-to-wake in normal sheep, transition into wake was abrupt in HD sheep. Furthermore, transitions to wake in normal sheep were preceded by a significant reduction in slow wave power, whereas in HD sheep this prior reduction in slow wave power was far less pronounced. This suggests an impaired ability to prepare for waking in HD sheep. The abruptness of awakenings may also have potential to disrupt sleep-dependent processes if they are interrupted in an untimely and disjointed manner. We propose that not only could these abnormal dynamics of sleep transitions be useful as an early biomarker of HD, but also that our novel methodology would be useful for studying transition dynamics in other sleep disorders.

A sleep spindle framework for motor memory consolidation.

Sleep spindle activity has repeatedly been found to contribute to brain plasticity and consolidation of both declarative and procedural memories. Here we propose a framework for motor memory consolidation that outlines the essential contribution of the hierarchical and multi-scale periodicity of spindle activity, as well as of the synchronization and interaction of brain oscillations during this sleep-dependent process. We posit that the clustering of sleep spindles in 'trains', together with the temporally organized alternation between spindles and associated refractory periods, is critical for efficient reprocessing and consolidation of motor memories. We further argue that the long-term retention of procedural memories relies on the synchronized (functional connectivity) local reprocessing of new information across segregated, but inter-connected brain regions that are involved in the initial learning process. Finally, we propose that oscillatory synchrony in the spindle frequency band may reflect the cross-structural reactivation, reorganization and consolidation of motor, and potentially declarative, memory traces within broader subcortical-cortical networks during sleep. This article is part of the Theo Murphy meeting issue 'Memory reactivation: replaying events past, present and future'.

Mathematical Models of Sleep and Circadian Rhythms: A Case for Using the 2-Process Model in Neuroscience Nursing.

Acute and chronic neurological disorders impair sleep. Despite the availability of theoretical/mathematical frameworks about sleep, the nursing profession rarely incorporates these models. The purpose of this article was to analyze the 2-process model of sleep regulation using Fawcett and DeSanto-Madeya's method, a systematic approach for determining whether a theory is relevant to nursing. The 2-process model has 3 concepts: process S (sleep-dependent process), process C (circadian-timing-dependent process), and total sleep propensity (summation of processes S and C). Nonnursing theories do not explicitly incorporate nursing metaparadigm concepts-person, health, environment, and nursing-but the 2-process model is congruent with nursing's philosophy. The model guided studies quantifying sleep and circadian patterns in other fields, and nurses could use this framework to measure the impact of nursing interventions. Strengths of the 2-process model include parsimony (conciseness without oversimplification) and the ability to empirically test propositions related to processes S and C. The 2-process model is relevant to neuroscience nursing-by measuring sleep/circadian-related variables (electroencephalogram, core body temperature, salivary melatonin). Nurses have opportunities to design, test, and use interventions that improve sleep in patients with neurological conditions.

Reduced Slow-Wave Sleep and Altered Diurnal Cortisol Rhythms in Patients with Addison's Disease.

Cortisol plays a key role in initiating and maintaining different sleep stages. Patients with Addison's disease (AD) frequently report disrupted sleep, and their hydrocortisone medication regimes do not restore the natural diurnal rhythm of cortisol. However, few studies have investigated relations between sleep quality, especially as measured by polysomnographic equipment, and night-time cortisol concentrations in patients with AD. We used sleep-adapted EEG to monitor a full night of sleep in 7 patients with AD and 7 healthy controls. We sampled salivary cortisol before bedtime, at midnight, upon awakening, and at 30-minutes post-waking. Controls had lower cortisol concentrations than patients before bedtime and at midnight. During the second half of the night, patient cortisol concentrations declined steeply, while control concentrations increased steadily. Whereas most controls experienced a positive cortisol awakening response, all patients experienced a decrease in cortisol concentrations from waking to 30-minutes post-waking (P = .003). Patients experienced significantly lower proportions of slow-wave sleep (SWS; P = .001), which was associated with elevated night-time cortisol concentrations. Overall, these results suggest that patients with AD demonstrate different patterns of night-time cortisol concentrations to healthy controls, and that relatively elevated concentrations are associated with a reduction of SWS. These hormonal and sleep architectural aberrations may disrupt the routine sleep-dependent processes of memory consolidation, and hence may explain, at least partially, the memory impairments often experienced by patients with AD.

Closed-Loop Slow-Wave tACS Improves Sleep-Dependent Long-Term Memory Generalization by Modulating Endogenous Oscillations.

Benefits in long-term memory retention and generalization have been shown to be related to sleep-dependent processes, which correlate with neural oscillations as measured by changes in electric potential. The specificity and causal role of these oscillations, however, are still poorly understood. Here, we investigated the potential for augmenting endogenous slow-wave (SW) oscillations in humans with closed-loop transcranial alternating current stimulation (tACS) with an aim toward enhancing the consolidation of recent experiences into long-term memory. Sixteen (three female) participants were trained presleep on a target detection task identifying targets hidden in complex visual scenes. During post-training sleep, closed-loop SW detection and stimulation were used to deliver tACS matching the phase and frequency of the dominant oscillation in the range of 0.5-1.2 Hz. Changes in performance were assessed the following day using test images that were identical to the training ("repeated"), and images generated from training scenes but with novel viewpoints ("generalized"). Results showed that active SW tACS during sleep enhanced the postsleep versus presleep target detection accuracy for the generalized images compared with sham nights, while no significant change was found for repeated images. Using a frequency-agnostic clustering approach sensitive to stimulation-induced spectral power changes in scalp EEG, this behavioral enhancement significantly correlated with both a poststimulation increase and a subsequent decrease in measured spectral power within the SW band, which in turn showed increased coupling with spindle amplitude. These results suggest that augmenting endogenous SW oscillations can enhance consolidation by specifically improving generalization over recognition or cued recall.SIGNIFICANCE STATEMENT This human study demonstrates the use of a closed-loop noninvasive brain stimulation method to enhance endogenous neural oscillations during sleep with the effect of improving consolidation of recent experiences into long-term memory. Here we show that transient slow oscillatory transcranial alternating current stimulation (tACS) triggered by endogenous slow oscillations and matching their frequency and phase can increase slow-wave power and coupling with spindles. Further, this increase correlates with overnight improvements in generalization of recent training to facilitate performance in a target detection task. We also provide novel evidence for a tACS-induced refractory period following the tACS-induced increase. Here slow-wave power is temporarily reduced relative to sham stimulation, which nonetheless maintains a positive relationship with behavioral improvements.

Neural reactivations during sleep determine network credit assignment.

A fundamental goal of motor learning is to establish neural patterns that produce a desired behavioral outcome. It remains unclear how and when the nervous system solves this “credit–assignment” problem. Using neuroprosthetic learning where we could control the causal relationship between neurons and behavior, here we show that sleep–dependent processing is required for credit-assignment and the establishment of task-related functional connectivity reflecting the casual neuron-behavior relationship. Importantly, we found a strong link between the microstructure of sleep reactivations and credit assignment, with downscaling of non–causal activity. Strikingly, decoupling of spiking to slow–oscillations using optogenetic methods eliminated rescaling. Thus, our results suggest that coordinated firing during sleep plays an essential role in establishing sparse activation patterns that reflect the causal neuron–behavior relationship.

Targeted Memory Reactivation during Sleep Adaptively Promotes the Strengthening or Weakening of Overlapping Memories.

System memory consolidation is conceptualized as an active process whereby newly encoded memory representations are strengthened through selective memory reactivation during sleep. However, our learning experience is highly overlapping in content (i.e., shares common elements), and memories of these events are organized in an intricate network of overlapping associated events. It remains to be explored whether and how selective memory reactivation during sleep has an impact on these overlapping memories acquired during awake time. Here, we test in a group of adult women and men the prediction that selective memory reactivation during sleep entails the reactivation of associated events and that this may lead the brain to adaptively regulate whether these associated memories are strengthened or pruned from memory networks on the basis of their relative associative strength with the shared element. Our findings demonstrate the existence of efficient regulatory neural mechanisms governing how complex memory networks are shaped during sleep as a function of their associative memory strength.SIGNIFICANCE STATEMENT Numerous studies have demonstrated that system memory consolidation is an active, selective, and sleep-dependent process in which only subsets of new memories become stabilized through their reactivation. However, the learning experience is highly overlapping in content and thus events are encoded in an intricate network of related memories. It remains to be explored whether and how memory reactivation has an impact on overlapping memories acquired during awake time. Here, we show that sleep memory reactivation promotes strengthening and weakening of overlapping memories based on their associative memory strength. These results suggest the existence of an efficient regulatory neural mechanism that avoids the formation of cluttered memory representation of multiple events and promotes stabilization of complex memory networks.

Emotional bias of sleep-dependent processing shifts from negative to positive with aging

Age-related memory decline has been proposed to result partially from impairments in memory consolidation over sleep. However, such decline may reflect a shift toward selective processing of positive information with age rather than impaired sleep-related mechanisms. In the present study, young and older adults viewed negative and neutral pictures or positive and neutral pictures and underwent a recognition test after sleep or wake. Subjective emotional reactivity and affect were also measured. Compared with waking, sleep preserved valence ratings and memory for positive but not negative pictures in older adults and negative but not positive pictures in young adults. In older adults, memory for positive pictures was associated with slow wave sleep. Furthermore, slow wave sleep predicted positive affect in older adults but was inversely related to positive affect in young adults. These relationships were strongest for older adults with high memory for positive pictures and young adults with high memory for negative pictures. Collectively, these results indicate preserved but selective sleep-dependent memory processing with healthy aging that may be biased to enhance emotional well-being.

Sleep physiology predicts memory retention after reactivation

Both sleep and future relevance influence memory consolidation; however, limited research has investigated their role in memory reconsolidation. We manipulated the future relevance of both stable and labile memories in need of reconsolidation. Two groups learned two blocks of syllable pairs on one evening and were told they would be tested on one of the blocks later. On the second evening, one group (Labile) received reminders designed to return their memories of syllable pairs to a labile state, while a second group (Stable) received reminders designed to leave these memories in a stable state. No significant differences in memory retention were found between blocks or groups the following morning. Frontal delta (0.5-4Hz) electroencephalographic power during Stage 2 sleep correlated positively with retention of future-relevant material exclusively in the Labile group. Central theta (4-8Hz) electroencephalographic power during rapid eye movement (REM) sleep correlated positively with the extent to which the Labile group selectively retained future-relevant material. These relationships suggest that sleep-dependent processes are involved in an economical reprocessing of memories beyond the initial stages of consolidation.

Neuronal Firing Rate Homeostasis Is Inhibited by Sleep and Promoted by Wake

Homeostatic mechanisms stabilize neural circuit function by keeping firing rates within a set-point range, but whether this process is gated by brain state is unknown. Here, we monitored firing rate homeostasis in individual visual cortical neurons in freely behaving rats as they cycled between sleep and wake states. When neuronal firing rates were perturbed by visual deprivation, they gradually returned to a precise, cell-autonomous set point during periods of active wake, with lengthening of the wake period enhancing firing rate rebound. Unexpectedly, this resetting of neuronal firing was suppressed during sleep. This raises the possibility that memory consolidation or other sleep-dependent processes are vulnerable to interference from homeostatic plasticity mechanisms. PAPERCLIP.

Maintaining vs. enhancing motor sequence memories: Respective roles of striatal and hippocampal systems

It is now accepted that hippocampal- and striatal-dependent memory systems do not act independently, but rather interact during both memory acquisition and consolidation. However, the respective functional roles of the hippocampus and the striatum in these processes remain unknown. Here, functional magnetic resonance imaging (fMRI) was used in a daytime sleep/wake protocol to investigate this knowledge gap. Using a protocol developed earlier in our lab (Albouy et al., 2013a), the manipulation of an explicit sequential finger-tapping task, allowed us to isolate allocentric (spatial) and egocentric (motor) representations of the sequence, which were supported by distinct hippocampo- and striato-cortical networks, respectively. Importantly, a sleep-dependent performance enhancement emerged for the hippocampal-dependent memory trace, whereas performance was maintained for the striatal-dependent memory trace, irrespective of the sleep condition. Regression analyses indicated that the interaction between these two systems influenced subsequent performance improvements. While striatal activity was negatively correlated with performance enhancement after both sleep and wakefulness in the allocentric representation, hippocampal activity was positively related to performance improvement for the egocentric representation, but only if sleep was allowed after training. Our results provide the first direct evidence of a functional dissociation in consolidation processes whereby memory stabilization seems supported by the striatum in a time-dependent manner whereas memory enhancement seems linked to hippocampal activity and sleep-dependent processes.

Sleep-dependent Neurophysiological Processes in Implicit Sequence Learning

Behavioral studies have cast doubts about the role that posttraining sleep may play in the consolidation of implicit sequence learning. Here, we used event-related fMRI to test the hypothesis that sleep-dependent functional reorganization would take place in the underlying neural circuits even in the possible absence of obvious behavioral changes. Twenty-four healthy human adults were scanned at Day 1 and then at Day 4 during an implicit probabilistic serial RT task. They either slept normally (RS) or were sleep-deprived (SD) on the first posttraining night. Unknown to them, the sequential structure of the material was based on a probabilistic finite-state grammar, with 15% chance on each trial of replacing the rules-based grammatical (G) stimulus with a nongrammatical (NG) one. Results indicated a gradual differentiation across sessions between RTs (faster RTs for G than NG), together with NG-related BOLD responses reflecting sequence learning. Similar behavioral patterns were observed in RS and SD participants at Day 4, indicating time- but not sleep-dependent consolidation of performance. Notwithstanding, we observed at Day 4 in the RS group a diminished differentiation between G- and NG-related neurophysiological responses in a set of cortical and subcortical areas previously identified as being part of the network involved in implicit sequence learning and its offline processing during sleep, indicating a sleep-dependent processing of both regular and deviant stimuli. Our results suggest the sleep-dependent development of distinct neurophysiological processes subtending consolidation of implicit motor sequence learning, even in the absence of overt behavioral differences.

The inhibitory effect of sleep deprivation on cell proliferation in the hippocampus of adult mice is eliminated by corticosterone clamp combined with interleukin-1 receptor 1 knockout

Deprivation or fragmentation of sleep for longer than 2days significantly inhibits cell proliferation and neurogenesis in the hippocampus of adult rats and mice. Signaling pathways that mediate these effects have yet to be clarified. Although deprivation procedures can stimulate adrenal corticosterone (CORT) release, suppression of cell proliferation by sleep deprivation does not require elevated CORT. We examined a role for interleukin-1β (IL-1β), a pro-inflammatory cytokine that is increased by sleep loss and that mediates effects of stress on hippocampal neurogenesis. Wild type (WT) and IL-1 receptor 1 knockout (IL1RI-KO) mice were subjected to rapid-eye-movement sleep deprivation (RSD) for 72-h using the multiple platform-over-water method. Mice were administered BrdU (100mg/kg) i.p. at hour 70 of RSD and were sacrificed 2-h later. New cells were identified by immunoreactivity (ir) for BrdU and Ki67 in the granular cell layer/subgranular zone (GCL/SGZ) and the hilus. In Experiment 1, WT and IL1RI-KO mice, by contrast with respective control groups, exhibited significantly fewer BrdU-ir and Ki67-ir cells. In Experiment 2, WT and IL1RI-KO mice were adrenalectomized (ADX) and maintained on constant low-dose CORT by osmotic minipumps. RSD reduced cell proliferation by 32% (p<0.01) in ADX-WT animals but did not significantly reduce proliferation in ADX IL1RI-KO animals (p>0.1). These results imply that RSD suppresses cell proliferation by the presence of wake-dependent factors (either elevated CORT or IL-1β signaling are sufficient), rather than the absence of a REM sleep-dependent process. The generality of these findings to other sleep deprivation methods and durations remains to be established.

Nocturnal sleep enhances working memory training in Parkinson's disease but not Lewy body dementia

Working memory is essential to higher order cognition (e.g. fluid intelligence) and to performance of daily activities. Though working memory capacity was traditionally thought to be inflexible, recent studies report that working memory capacity can be trained and that offline processes occurring during sleep may facilitate improvements in working memory performance. We utilized a 48-h in-laboratory protocol consisting of repeated digit span forward (short-term attention measure) and digit span backward (working memory measure) tests and overnight polysomnography to investigate the specific sleep-dependent processes that may facilitate working memory performance improvements in the synucleinopathies. We found that digit span backward performance improved following a nocturnal sleep interval in patients with Parkinson's disease on dopaminergic medication, but not in those not taking dopaminergic medication and not in patients with dementia with Lewy bodies. Furthermore, the improvements in patients with Parkinson's disease on dopaminergic medication were positively correlated with the amount of slow-wave sleep that patients obtained between training sessions and negatively correlated with severity of nocturnal oxygen desaturation. The translational implication is that working memory capacity is potentially modifiable in patients with Parkinson's disease but that sleep disturbances may first need to be corrected.

Sleep and environmental context: interactive effects for memory

Sleep after learning is often beneficial for memory. Reinstating an environmental context that was present at learning during subsequent retrieval also leads to superior declarative memory performance. This study examined how post-learning sleep, relative to wakefulness, impacts upon context-dependent memory effects. Thirty-two participants encoded word lists in each of two rooms (contexts), which were different in terms of size, odour and background music. Immediately after learning and following a night of sleep or a day of wakefulness, memory for all previously studied words was tested using a category-cued recall task in room one or two alone. Accordingly, a comparison could be made between words retrieved in an environmental context which was the same as, or different to, that of the learning phase. Memory performance was assessed by the difference between the number of words remembered at immediate and delayed retrieval. A 2×2×2 mixed ANOVA revealed an interaction between retrieval context (same/different to learning) and retention interval (sleep/wakefulness), which was driven by superior memory after sleep than after wake when learning and retrieval took place in different environmental contexts. Our findings suggest a sleep-related reduction in the extent to which context impacts upon retrieval. As such, these data provide initial support for the possibility that sleep dependent processes may promote a decontextualisation of recently formed declarative representations.

How do I remember? Let me count the ways

In this issue, Diekelmann, Wilhelm and Born1 provide an extensive and critical review of the rapidly growing literature on sleep-dependent memory consolidation. But rather than simply reviewing this literature, they have taken this opportunity to ask several important questions concerning off-line memory processing. Most gratifying is their decision not to simply look ever more deeply into frequently discussed questions, but rather to raise several new ones. They ask what kinds of memories are consolidated by sleep, what kinds of consolidation are accomplished, and what kinds of sleep are required. For the reader looking for a quick set of answer, they won't find them here or in the Diekelmann article. But the authors have done a superb job of organize the literature to support a series of proposed answers, and I will offer a few more, all of which will hopefully serve as a basis for further investigations. The task of sorting out the interactions between sleep and memory is a daunting one. We summarized some of these issues in an earlier review.2 At the very least (Fig 1), one has to address the question of how five stages of sleep3 interact with at least six types of memories4 and six stages of post-encoding memory processing,2 for a combined total of 144 distinct sub-questions (e.g., how does REM sleep affect the stabilization of classical conditioning; Fig 1). But Diekelmann and colleagues have now added another layer of more subtle questions – how do the strength of initial encoding and the perceived value of the memory interact with these sleep-dependent processes, how do the amount of sleep and the timing of the sleep affect them, and how do these processes change with age and in the presence of psychiatric disorders? Open in a separate window Figure 1 The sleep cycle, memory systems, and memory stages (A) The human sleep cycle—across the night, NREM and REM sleep cycle every 90 min in an ultradian manner, while the ratio of NREM to REM sleep shifts. During the first half of the night, stages 3 and 4 NREM (SWS) dominate, while stage 2 NREM and REM sleep prevail in the latter half of the night. EEG patterns also differ significantly between sleep stages, with electrical oscillations such as K complexes and sleep spindles occurring during stage 2 NREM, slow (0.5–4Hz) delta waves developing in SWS, and theta waves seen during REM. (B) Memory systems—human memory is most commonly divided into declarative forms, with further subdivisions into episodic and semantic; and nondeclarative forms, subdivided into an array of different types including procedural skill memory (C) Developing stages of memory—following the initial encoding of a memory, several ensuing stages are proposed, beginning with consolidation, as well as integration of the memory representation, translocation of the representation, or erasure of the memory. Also, following later recall, the memory representation is believed to become unstable once again, requiring periods of reconsolidation. Reproduced from 2.

Sleep improves sequential motor learning and performance in patients with prefrontal lobe lesions

Objectives Motor skill learning involves both practice and a latent, sleep-dependent process of consolidation that develops after training (“off-line” learning). Sleep consolidation is linked to reduced brain activation in prefrontal areas, along with strong involvement of parietal regions. The objective in this study was to investigate the influence of sleep on the consolidation process of a motor task in patients with prefrontal damage. Patients and methods For that purpose 14 patients with acquired focal prefrontal lesions, 15 age-matched healthy controls, and five patients with parietal lesions were evaluated on a serial reaction time task, SRTT, before and after a night of monitored sleep. Verbal and working memory was also tested. We anticipated that patients with prefrontal lesions, who are impaired in the acquisition of motor tasks, would benefit greater from sleep than the other two groups, since consolidation does not depend on prefrontal regions. Results Prefrontal patients showed an erratic learning curve at night, with great inter- and intrasubject variability that normalized after sleep. They also showed higher overnight learning of the motor skill and improvement on speed performance on the SRTT. No differences in the other memory tests were found between sessions. Conclusion Prefrontal-injured patients benefit from night sleep in terms of motor task learning and performance, likely related to an advantageous off-line learning. Sleep could play a role in motor rehabilitation programs in prefrontal patients.