Search

Aims/hypothesis Sleep, diet and exercise are fundamental to metabolic homeostasis. In this secondary analysis of a repeated measures, nutritional intervention study, we tested whether an individual’s sleep quality, duration and timing impact glycaemic response to a breakfast meal the following morning. Methods Healthy adults’ data (N = 953 [41% twins]) were analysed from the PREDICT dietary intervention trial. Participants consumed isoenergetic standardised meals over 2 weeks in the clinic and at home. Actigraphy was used to assess sleep variables (duration, efficiency, timing) and continuous glucose monitors were used to measure glycaemic variation (>8000 meals). Results Sleep variables were significantly associated with postprandial glycaemic control (2 h incremental AUC), at both between- and within-person levels. Sleep period time interacted with meal type, with a smaller effect of poor sleep on postprandial blood glucose levels when high-carbohydrate (low fat/protein) (pinteraction = 0.02) and high-fat (pinteraction = 0.03) breakfasts were consumed compared with a reference 75 g OGTT. Within-person sleep period time had a similar interaction (high carbohydrate: pinteraction = 0.001, high fat: pinteraction = 0.02). Within- and between-person sleep efficiency were significantly associated with lower postprandial blood glucose levels irrespective of meal type (both p p = 0.035 and p = 0.051, respectively). Conclusions/interpretation Poor sleep efficiency and later bedtime routines are associated with more pronounced postprandial glycaemic responses to breakfast the following morning. A person’s deviation from their usual sleep pattern was also associated with poorer postprandial glycaemic control. These findings underscore sleep as a modifiable, non-pharmacological therapeutic target for the optimal regulation of human metabolic health. Trial registrationClinicalTrials.gov NCT03479866. Graphical abstract

Poor sleep is associated with hypertension, a major risk factor for cardiovascular disease. However, the mechanism(s) through which sleep loss affects cardiovascular health remains largely unknown, including the brain and body systems that regulate vascular function.Sixty-six healthy adults participated in a repeated-measures, crossover, experimental study involving assessments of cardiovascular function and brain connectivity after a night of sleep and a night of sleep deprivation.First, sleep deprivation significantly increased blood pressure-both systolic and diastolic. Interestingly, this change was independent of any increase in heart rate, inferring a vasculature-specific rather than direct cardiac pathway. Second, sleep loss compromised functional brain connectivity within the vascular control network, specifically the insula, anterior cingulate, amygdala, and ventral and medial prefrontal cortices. Third, sleep loss-related changes in brain connectivity and vascular tone were not independent, but significantly interdependent, with changes within the vascular control brain network predicting the sleep-loss shift toward hypertension.These findings establish an embodied framework in which sleep loss confers increased risk of cardiovascular disease through an impact upon central brain control of vascular tone, rather than a direct impact on accelerated heart rate itself.

How people wake up and regain alertness in the hours after sleep is related to how they are sleeping, eating, and exercising. Here, in a prospective longitudinal study of 833 twins and genetically unrelated adults, we demonstrate that how effectively an individual awakens in the hours following sleep is not associated with their genetics, but instead, four independent factors: sleep quantity/quality the night before, physical activity the day prior, a breakfast rich in carbohydrate, and a lower blood glucose response following breakfast. Furthermore, an individual’s set-point of daily alertness is related to the quality of their sleep, their positive emotional state, and their age. Together, these findings reveal a set of non-genetic (i.e., not fixed) factors associated with daily alertness that are modifiable.

Humans help each other. This fundamental feature of homo sapiens has been one of the most powerful forces sculpting the advent of modern civilizations. But what determines whether humans choose to help one another? Across 3 replicating studies, here, we demonstrate that sleep loss represents one previously unrecognized factor dictating whether humans choose to help each other, observed at 3 different scales (within individuals, across individuals, and across societies). First, at an individual level, 1 night of sleep loss triggers the withdrawal of help from one individual to another. Moreover, fMRI findings revealed that the withdrawal of human helping is associated with deactivation of key nodes within the social cognition brain network that facilitates prosociality. Second, at a group level, ecological night-to-night reductions in sleep across several nights predict corresponding next-day reductions in the choice to help others during day-to-day interactions. Third, at a large-scale national level, we demonstrate that 1 h of lost sleep opportunity, inflicted by the transition to Daylight Saving Time, reduces real-world altruistic helping through the act of donation giving, established through the analysis of over 3 million charitable donations. Therefore, inadequate sleep represents a significant influential force determining whether humans choose to help one another, observable across micro- and macroscopic levels of civilized interaction. The implications of this effect may be non-trivial when considering the essentiality of human helping in the maintenance of cooperative, civil society, combined with the reported decline in sufficient sleep in many first-world nations.

How people wake up and regain alertness in the hours after sleep is related to how they are sleeping, eating, and exercising. Here, in a prospective longitudinal study of 833 twins and genetically unrelated adults, we demonstrate that how effectively an individual awakens in the hours following sleep is not associated with their genetics, but instead, four independent factors: sleep quantity/quality the night before, physical activity the day prior, a breakfast rich in carbohydrate, and a lower blood glucose response following breakfast. Furthermore, an individual's set-point of daily alertness is related to the quality of their sleep, their positive emotional state, and their age. Together, these findings reveal a set of non-genetic (i.e., not fixed) factors associated with daily alertness that are modifiable.

Why does poor-quality sleep lead to atherosclerosis? In a diverse sample of over 1,600 individuals, we describe a pathway wherein sleep fragmentation raises inflammatory-related white blood cell counts (neutrophils and monocytes), thereby increasing atherosclerosis severity, even when other common risk factors have been accounted for. Improving sleep quality may thus represent one preventive strategy for lowering inflammatory status and thus atherosclerosis risk, reinforcing public health policies focused on sleep health., Why does poor quality sleep correlate with cardiovascular disease? A large population-based study suggests that fragmented sleep contributes to atherosclerosis in humans by increasing inflammatory-related activity of white blood cells.

Are you feeling emotionally fragile, moody, unpredictable, even ungenerous to those around you? Here, we review how and why these phenomena can occur as a result of insufficient sleep. Sleep loss disrupts a broad spectrum of affective processes, from basic emotional operations (e.g., recognition, responsivity, expression), through to high-order, complex socio-emotional functioning (e.g., loneliness, helping behavior, abusive behavior, and charisma). Translational insights further emerge regarding the pervasive link between sleep disturbance and psychiatric conditions, including anxiety, depression, and suicidality. More generally, such findings raise concerns regarding society's mental (ill)health and the prevalence of insufficient and disrupted sleep.

Deep non-rapid eye movement sleep (NREM) and general anesthesia with propofol are prominent states of reduced arousal linked to the occurrence of synchronized oscillations in the electroencephalogram (EEG). Although rapid eye movement (REM) sleep is also associated with diminished arousal levels, it is characterized by a desynchronized, ‘wake-like’ EEG. This observation implies that reduced arousal states are not necessarily only defined by synchronous oscillatory activity. Using intracranial and surface EEG recordings in four independent data sets, we demonstrate that the 1/f spectral slope of the electrophysiological power spectrum, which reflects the non-oscillatory, scale-free component of neural activity, delineates wakefulness from propofol anesthesia, NREM and REM sleep. Critically, the spectral slope discriminates wakefulness from REM sleep solely based on the neurophysiological brain state. Taken together, our findings describe a common electrophysiological marker that tracks states of reduced arousal, including different sleep stages as well as anesthesia in humans., eLife digest Electroencephalogram (EEG for short) is a widespread technique that helps to monitor the electrical activity of the brain. In particular, it can be used to examine, recognize and compare different states of brain consciousness such as sleep, wakefulness or general anesthesia. Yet, during rapid eye movement sleep (the sleep phase in which dreaming occurs), the electrical activity of the brain is similar to the one recorded during wakefulness, making it difficult to distinguish these states based on EEG alone. EEG records brain activity in the shape of rhythmic waves whose frequency, shape and amplitude vary depending on the state of consciousness. In the EEG signal from the human brain, the higher frequency waves are weaker than the low-frequency waves: a measure known as spectral slope reflects the degree of this difference in the signal strength. Previous research suggests that spectral slope can be used to distinguish wakefulness from anesthesia and non-REM sleep. Here, Lendner et al. explored whether certain elements of the spectral slope could also discern wakefulness from all states of reduced arousal. EEG readings were taken from patients and volunteers who were awake, asleep or under anesthesia, using electrodes placed either on the scalp or into the brain. Lendner et al. found that the spectral slope could distinguish wakefulness from anesthesia, deep non-REM and REM sleep. The changes in the spectral slope during sleep could accurately track the degree of arousal with great temporal precision and across a wide range of time scales. This method means that states of consciousness can be spotted just from a scalp EEG. In the future, this approach could be embedded into the techniques used for monitoring sleep or anesthesia during operations; it could also be harnessed to monitor other low-response states, such as comas.

OBJECTIVE Sleep prepares key neural structures for next-day learning, and sleep obtained after learning promotes subsequent memory consolidation supporting long-term retention. This study examined whether sleep the night before and after a therapy session predicts aspects of treatment adherence. METHOD As part of a randomized clinical trial, 188 adults (62.7% female, mean age = 47.5, 80.5% Caucasian) with persistent insomnia received cognitive-behavioral therapy for insomnia. Patients completed a sleep diary before and after treatment sessions. Minutes spent awake during the night (total wake time; TWT) and total sleep time (TST) were used as measures of sleep disturbance. At each treatment session, therapists rated participant understanding of the session and homework compliance from the previous session. RESULTS Compared to longer TWT, before session shorter TWT was associated with increased treatment understanding the next day. After session shorter TWT was also associated with increased understanding, but not homework compliance the subsequent session compared to participants with longer TWT. Similar results were obtained for TST. CONCLUSIONS Improving sleep may benefit patient adherence to treatment. Sleep may influence processes related to initial learning and subsequent consolidation of treatment information. Future studies should examine whether improved sleep within other psychiatric disorders is also an ingredient to the successful outcome of psychosocial interventions. (PsycINFO Database Record

Older adults do not sleep as well as younger adults. Why? What alterations in sleep quantity and quality occur as we age, and are there functional consequences? What are the underlying neural mechanisms that explain age-related sleep disruption? This review tackles these questions. First, we describe canonical changes in human sleep quantity and quality in cognitively normal older adults. Second, we explore the underlying neurobiological mechanisms that may account for these human sleep alterations. Third, we consider the functional consequences of age-related sleep disruption, focusing on memory impairment as an exemplar. We conclude with a discussion of a still-debated question: do older adults simply need less sleep, or rather, are they unable to generate the sleep that they still need?

Rapidly emerging evidence continues to describe an intimate and causal relationship between sleep and emotional brain function. These findings are mirrored by long-standing clinical observations demonstrating that nearly all mood and anxiety disorders co-occur with one or more sleep abnormalities. This review aims to (a) provide a synthesis of recent findings describing the emotional brain and behavioral benefits triggered by sleep, and conversely, the detrimental impairments following a lack of sleep; (b) outline a proposed framework in which sleep, and specifically rapid-eye movement (REM) sleep, supports a process of affective brain homeostasis, optimally preparing the organism for next-day social and emotional functioning; and (c) describe how this hypothesized framework can explain the prevalent relationships between sleep and psychiatric disorders, with a particular focus on posttraumatic stress disorder and major depression.

Sleep is strongly conserved within species, yet marked and perplexing inter-individual differences in sleep physiology are observed. Combining EEG sleep recordings and high-resolution structural brain imaging, here we demonstrate that the morphology of the human brain offers one explanatory factor of such inter-individual variability. Grey matter volume in interoceptive and exteroceptive cortices correlated with the expression of slower NREM sleep spindle frequencies, supporting their proposed role in sleep protection against conscious perception. Conversely, and consistent with an involvement in declarative memory processing, grey matter volume in bilateral hippocampus was associated with faster NREM sleep spindle frequencies. In contrast to spindles, grey matter volume in the homeostatic sleep-regulating center of the basal forebrain/hypothalamus, together with the medial prefrontal cortex, accounted for individual differences in NREM slow wave oscillations. Together, such findings indicate that the qualitative and quantitative expression of human sleep physiology is significantly related to anatomically specific differences in macroscopic brain structure.

© The Author 2013. Published by Oxford University Press. All rights reserved. A hallmark feature of cognitive aging is a decline in the ability to form new memories. Parallel to these cognitive impairments are marked disruptions in sleep physiology. Despite recent evidence in young adults establishing a role for sleep spindles in restoring hippocampaldependent memory formation, the possibility that disrupted sleep physiology contributes to age-related decline in hippocampaldependent learning remains unknown. Here, we demonstrate that reduced prefrontal sleep spindles by over 40% in older adults statistically mediates the effects of old age on next day episodic learning, such that the degree of impaired episodic learning is explained by the extent of impoverished prefrontal sleep spindles. In addition, prefrontal spindles significantly predicted the magnitude of impaired next day hippocampal activation, thereby determining the influence of spindles on post-sleep learning capacity. These data support the hypothesis that disrupted sleep physiology contributes to age-related cognitive decline in later life, the consequence of which has significant treatment intervention potential.

Aging has independently been associated with regional brain atrophy, reduced slow wave activity (SWA) during non-rapid eye movement (NREM) sleep and impaired long-term retention of episodic memories. However, whether the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. We found that age- related medial prefrontal cortex (mPFC) gray-matter atrophy was associated with reduced NREM SWA in older adults, the extent to which statistically mediated the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex functional connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represents a contributing factor to age-related cognitive decline in later life.

Summary The default mode network (DMN) is a commonly observed resting-state network (RSN) that includes medial temporal, parietal, and prefrontal regions involved in episodic memory [1, 2, 3]. The behavioral relevance of endogenous DMN activity remains elusive, despite an emerging literature correlating resting fMRI fluctuations with memory performance [4, 5]—particularly in DMN regions [6, 7, 8]. Mechanistic support for the DMN’s role in memory consolidation might come from investigation of large deflections (sharp-waves) in the hippocampal local field potential that co-occur with high-frequency (>80 Hz) oscillations called ripples—both during sleep [9, 10] and awake deliberative periods [11, 12, 13]. Ripples are ideally suited for memory consolidation [14, 15], since the reactivation of hippocampal place cell ensembles occurs during ripples [16, 17, 18, 19]. Moreover, the number of ripples after learning predicts subsequent memory performance in rodents [20, 21, 22] and humans [23], whereas electrical stimulation of the hippocampus after learning interferes with memory consolidation [24, 25, 26]. A recent study in macaques showed diffuse fMRI neocortical activation and subcortical deactivation specifically after ripples [27]. Yet it is unclear whether ripples and other hippocampal neural events influence endogenous fluctuations in specific RSNs—like the DMN—unitarily. Here, we examine fMRI datasets from anesthetized monkeys with simultaneous hippocampal electrophysiology recordings, where we observe a dramatic increase in the DMN fMRI signal following ripples, but not following other hippocampal electrophysiological events. Crucially, we find increases in ongoing DMN activity after ripples, but not in other RSNs. Our results relate endogenous DMN fluctuations to hippocampal ripples, thereby linking network-level resting fMRI fluctuations with behaviorally relevant circuit-level neural dynamics., Highlights • Behavioral relevance of offline fluctuations in the default mode network is unclear • Hippocampal sharp-wave ripples during rest are linked with memory consolidation • Default mode network signal increases after ripples, but not other hippocampal events • Other neocortical resting-state networks do not show similar changes after ripples, Kaplan et al. show that offline fMRI signal fluctuations throughout the default mode network (DMN), which includes neocortical regions important for episodic memory, are uniformly influenced by hippocampal sharp-wave ripples. These results relate ongoing DMN fluctuations to the consolidation of past experience and preparation for future behavior.

Sleep disruption appears to be a core component of Alzheimer's disease (AD) and its pathophysiology. Signature abnormalities of sleep emerge before clinical onset of AD. Moreover, insufficient sleep facilitates accumulation of amyloid-β (Aβ), potentially triggering earlier cognitive decline and conversion to AD. Building on such findings, this review has four goals: evaluating (i) associations and plausible mechanisms linking non-rapid-eye-movement (NREM) sleep disruption, Aβ, and AD; (ii) a role for NREM sleep disruption as a novel factor linking cortical Aβ to impaired hippocampus-dependent memory consolidation; (iii) the potential diagnostic utility of NREM sleep disruption as a new biomarker of AD; and (iv) the possibility of sleep as a new treatment target in aging, affording preventative and therapeutic benefits.

Ample evidence supports a role for sleep in the offline consolidation of memory. However, circumstances exist where forgetting can be as critical as remembering, both in daily life and clinically. Using a directed forgetting paradigm, here, we investigate the impact of explicit cue instruction during learning, prior to sleep, on subsequent remembering and forgetting of memory, after sleep. We demonstrate that sleep, relative to time awake, can selectively ignore the facilitation of items previously cued to be forgotten, yet preferentially enhance recall for items cued to be remembered; indicative of specificity based on prior waking instruction. Moreover, the success of this differential remember/forget effect is strongly correlated with fast sleep spindles over the left superior parietal cortex. Furthermore, electroencephalography source analysis of these spindles revealed a repeating loop of current density between selective memory-related regions of the superior parietal, medial temporal, and right prefrontal cortices. These findings move beyond the classical notion of sleep universally strengthening information. Instead, they suggest a model in which sleep may be more ecologically attuned to instructions present during learning while awake, supporting both remembering and targeted forgetting of human memories.

Temporal processing forms the basis of a vast number of human behaviours, from simple perception and action to tasks like locomotion, playing a musical instrument, and understanding language. Growing evidence suggests that these procedural skills are consolidated during sleep, however investigation of such learning has focused upon the order in which movements are made rather than their temporal dynamics. Here, we use psychophysics and neuroimaging to explore the possibility that temporal aspects of such skills are also enhanced over a period of sleep. Behaviourally, our examinations of motor (tapping a finger in time with a temporal rhythm) and perceptual (monitoring a temporal rhythm for deviants) tasks reveal post-sleep improvements in both domains. Functionally, we show that responses in striatum, supplementary motor area, and lateral cerebellum are stronger during motor, but not during perceptual timing post-sleep. Conversely, responses in posterior hippocampus are stronger during perceptual, but not motor timing post-sleep. Our data support the proposal that these two forms of timing draw on different brain mechanisms, with motor timing using a more automatic system while perceptual timing of the same rhythm requires a more cognitive form of processing.

This study assessed the effects of ecstasy/MDMA on declarative memory (Rivermead Behavioral Memory task - RBMT), on procedural learning (Finger Tapping Task - FTT), and on the memory consolidation function of sleep for these two tasks. Testing occurred in 2 afternoon testing sessions, 24 hours apart so that a full period of sleep was allowed between them. Groups were: Non-drug taking Controls (n=24); Recent Ecstasy/MDMA users, who had taken ecstasy and/or MDMA 2–3 days before the first testing session (n=25), and Abstinent Ecstasy/MDMA users, who had not taken ecstasy/MDMA for at least 8 days before the first session (n=17). The recent ecstasy/MDMA users performed significantly worse than controls on the RBMT (mean recall 76.1% of control group recall), but did not differ from controls on FTT performance. Correspondingly there was a significant regression between the continuous variable of recency of ecstasy/MDMA use and RBMT performance. However, there was an interaction between ecstasy/MDMA use and subsequent other drug use. Controls had similar RBMT scores to recent ecstasy/MDMA users who did not take other drugs 48 – 24 hours before testing, but scored significantly better than recent ecstasy/MDMA users who took various other drugs (mainly cannabis) 48 – 24 hours before testing. For both tasks the control, recent ecstasy/MDMA and abstinent ecstasy/MDMA users did not differ in their change of performance across 24 hours; there was thus no evidence that ecstasy/MDMA impairs the memory consolidation function of sleep for either declarative or procedural memory. For participants in the two ecstasy/MDMA groups greater lifetime consumption of ecstasy tablets was associated with significantly more deficits in procedural memory. Furthermore, greater lifetime consumption of ecstasy tablets and of cocaine, were also associated with significantly more deficits in declarative memory.

The coupled interaction between slow-wave oscillations and sleep spindles during non-rapid-eye-movement (NREM) sleep has been proposed to support memory consolidation. However, little evidence in humans supports this theory. Moreover, whether such dynamic coupling is impaired as a consequence of brain aging in later life, contributing to cognitive and memory decline, is unknown. Combining electroencephalography (EEG), structural MRI, and sleep-dependent memory assessment, we addressed these questions in cognitively normal young and older adults. Directional cross-frequency coupling analyses demonstrated that the slow wave governs a precise temporal coordination of sleep spindles, the quality of which predicts overnight memory retention. Moreover, selective atrophy within the medial frontal cortex in older adults predicted a temporal dispersion of this slow wave-spindle coupling, impairing overnight memory consolidation and leading to forgetting. Prefrontal-dependent deficits in the spatiotemporal coordination of NREM sleep oscillations therefore represent one pathway explaining age-related memory decline.

Memories are not stored as exact copies of our experiences. As a result, remembering is subject not only to memory failure, but to inaccuracies and distortions as well. Although such distortions are often retained or even enhanced over time, sleep's contribution to the development of false memories is unknown. Here, we report that a night of sleep increases both veridical and false recall in the Deese-Roediger-McDermott (DRM) paradigm, compared to an equivalent period of daytime wakefulness. But while veridical memory deteriorates across both wake and sleep, false memories are preferentially preserved by sleep, actually showing a non-significant improvement. The same selectivity of false over veridical memories was observed in a follow-up nap study. Unlike previous studies implicating deep, slow-wave sleep (SWS) in declarative memory consolidation, here veridical recall correlated with decreased SWS, a finding that was observed in both the overnight and nap studies. These findings lead to two counterintuitive conclusions - that under certain circumstances sleep can promote false memories over veridical ones, and SWS can be associated with impairment rather than facilitation of declarative memory consolidation. While these effects produce memories that are less accurate after sleep, these memories may, in the end, be more useful.

As critical as waking brain function is to cognition, an extensive literature now indicates that sleep supports equally important, different yet complementary operations. This review will consider recent and emerging findings implicating sleep and specific sleep-stage physiologies in the modulation, regulation, and even preparation of cognitive and emotional brain processes. First, evidence for the role of sleep in memory processing will be discussed, principally focusing on declarative memory. Second, at a neural level several mechanistic models of sleep-dependent plasticity underlying these effects will be reviewed, with a synthesis of these features offered that may explain the ordered structure of sleep, and the orderly evolution of memory stages. Third, accumulating evidence for the role of sleep in associative memory processing will be discussed, suggesting that the long-term goal of sleep may not be the strengthening of individual memory items, but, instead, their abstracted assimilation into a schema of generalized knowledge. Fourth, the newly emerging benefit of sleep in regulating emotional brain reactivity will be considered. Finally, and building on this latter topic, a novel hypothesis and framework of sleep-dependent affective brain processing will be proposed, culminating in testable predictions and translational implications for mood disorders.

Although we still lack any consensus function(s) for sleep, accumulating evidence suggests it plays an important role in homeostatic restoration, thermoregulation, tissue repair, immune control and memory processing. In the last decade an increasing number of reports continue to support a bidirectional and symbiotic relationship between sleep and memory. Studies using procedural and declarative learning tasks have demonstrated the need for sleep after learning in the offline consolidation of new memories. Furthermore, these consolidation benefits appear to be mediated by an overnight neural reorganization of memory that may result in a more efficient storage of information, affording improved next-day recall. Sleep before learning also appears to be critical for brain functioning. Specifically, one night of sleep deprivation markedly impairs hippocampal function, imposing a deficit in the ability to commit new experiences to memory. Taken together, these observations are of particular ecologic importance from a professional and education perspective when considering that sleep time continues to decrease across all age ranges throughout industrialized nations.

Both sleep and emotion are known to modulate processes of memory consolidation, yet their interaction is poorly understood. We examined the influence of sleep on consolidation of emotionally arousing and neutral declarative memory. Subjects completed an initial study session involving arousing and neutral pictures, either in the evening or in the morning. Twelve hours later, after sleeping or staying awake, subjects performed a recognition test requiring them to discriminate between these original pictures and novel pictures by responding “remember,” “know” (familiar), or “new.” Selective sleep effects were observed for consolidation of emotional memory: Recognition accuracy for know judgments of arousing stimuli improved by 42% after sleep relative to wake, and recognition bias for remember judgments of these stimuli increased by 58% after sleep relative to wake (resulting in more conservative responding). These findings hold important implications for understanding of human memory processing, suggesting that the facilitation of memory for emotionally salient information may preferentially develop during sleep.

Mental disorders are prevalent and lead to significant impairment. Progress toward establishing treatments has been good. However, effect sizes are small to moderate, gains may not persist, and many patients derive no benefit. Our goal is to highlight the potential for empirically-supported psychosocial treatments to be improved by incorporating insights from cognitive psychology and research on education. Our central question is: If it were possible to improve memory for content of sessions of psychosocial treatments, would outcome substantially improve? This question arises from five lines of evidence: (a) mental illness is often characterized by memory impairment, (b) memory impairment is modifiable, (c) psychosocial treatments often involve the activation of emotion, (d) emotion can bias memory and (e) memory for psychosocial treatment sessions is poor. Insights from scientific knowledge on learning and memory are leveraged to derive strategies for a transdiagnostic and transtreatment cognitive support intervention. These strategies can be applied within and between sessions and to interventions delivered via computer, the internet and text message. Additional novel pathways to improving memory include improving sleep, engaging in exercise and imagery. Given that memory processes change across the lifespan, services to children and older adults may benefit from cognitive support.

Although there is no consensus regarding the functions of sleep, one exciting hypothesis is that sleep contributes importantly to learning and memory. Over the last decade, several studies have provided substantive evidence supporting the role of sleep in memory processing. This article focuses on sleep-dependent learning and brain plasticity in humans, specifically in the development of skill performance that is the foundation of many sports actions. The different forms and stages of human memory are discussed, then evidence of sleep-dependent skill learning and associated sleep-dependent brain plasticity is described. In conclusion, a consideration of the fundamental importance of sleep in real-life skill learning is provided.

Learning of procedural skills develops gradually, with performance improving significantly with practice. But improvement on some tasks, including a visual texture discrimination task, continues in the absence of further practice, expressly during periods of sleep and not across equivalent waking episodes. Here we report that the brain activation revealed significantly different patterns of performance-related functional activity following a night of sleep relative to 1 h post-training without intervening sleep. When task activation patterns after a night of sleep were compared with activation patterns without intervening sleep (1 h post-training), significant regions of increased signal intensity were observed in the primary visual cortex, the occipital temporal junction, the medial temporal lobe and the inferior parietal lobe. In contrast, a region of decreased signal intensity was found in the right temporal pole. Corroborating these condition differences, correlations between behavioural performance and brain activation revealed significantly different patterns of performance-related functional activity following a night of sleep relative to those without intervening sleep. Together, these data provide evidence of overnight bi-directional changes in functional anatomy, differences that may form the neural basis of sleep-dependent learning expressed on this task.

Research in the neurosciences continues to provide evidence that sleep plays a role in the processes of learning and memory. There is less of a consensus, however, regarding the precise stages of memory development during which sleep is considered a requirement, simply favorable, or not important. This article begins with an overview of recent studies regarding sleep and learning, predominantly in the procedural memory domain, and is measured against our current understanding of the mechanisms that govern memory formation. Based on these considerations, I offer a new neurocognitive framework of procedural learning, consisting first of acquisition, followed by two specific stages of consolidation, one involving a process of stabilization, the other involving enhancement, whereby delayed learning occurs. Psychophysiological evidence indicates that initial acquisition does not rely fundamentally on sleep. This also appears to be true for the stabilization phase of consolidation, with durable representations, resistant to interference, clearly developing in a successful manner during time awake (or just time, per se). In contrast, the consolidation stage, resulting in additional/enhanced learning in the absence of further rehearsal, does appear to rely on the process of sleep, with evidence for specific sleep-stage dependencies across the procedural domain. Evaluations at a molecular, cellular, and systems level currently offer several sleep specific candidates that could play a role in sleep-dependent learning. These include the upregulation of select plasticity-associated genes, increased protein synthesis, changes in neurotransmitter concentration, and specific electrical events in neuronal networks that modulate synaptic potentiation.

Growing evidence indicates a role for sleep in off-line memory processing, specifically in post-training consolidation. In humans, sleep has been shown to trigger overnight learning on a motor-sequence memory task, while equivalent waking periods produce no such improvement. But while the behavioral characteristics of sleep-dependent motor learning become increasingly well characterized, the underlying neural basis remains unknown. Here we present functional magnetic resonance imaging data demonstrating a change in the representation of a motor memory after a night of sleep. Subjects trained on a motor-skill memory and 12 hours later, after either sleep or wake, were retested during functional magnetic resonance imaging. Following sleep relative to wake, regions of increased activation were expressed in the right primary motor cortex, medial prefrontal lobe, hippocampus and left cerebellum; changes that can support faster motor output and more precise mapping of key-press movements. In contrast, signal decreases were identified in parietal cortices, the left insular cortex, temporal pole and fronto-polar region, reflecting a reduced need for conscious spatial monitoring and a decreased emotional task burden. This evidence of an overnight, systems-level change in the representation of a motor memory holds important implications for acquiring real-life skills and in clinical rehabilitation following brain trauma, such as stroke.

Learning of a procedural motor-skill task is known to progress through a series of unique memory stages. Performance initially improves during training, and continues to improve, without further rehearsal, across subsequent periods of sleep. Here, we investigate how this delayed sleep-dependent learning is affected when the task characteristics are varied across several degrees of difficulty, and whether this improvement differentially enhances individual transitions of the motor-sequence pattern being learned. We report that subjects show similar overnight improvements in speed whether learning a five-element unimanual sequence (17.7% improvement), a nine-element unimanual sequence (20.2%), or a five-element bimanual sequence (17.5%), but show markedly increased overnight improvement (28.9%) with a nine-element bimanual sequence. In addition, individual transitions within the motor-sequence pattern that appeared most difficult at the end of training showed a significant 17.8% increase in speed overnight, whereas those transitions that were performed most rapidly at the end of training showed only a non-significant 1.4% improvement. Together, these findings suggest that the sleep-dependent learning process selectively provides maximum benefit to motor-skill procedures that proved to be most difficult prior to sleep.

Evidence continues to support a role for sleep in delayed learning without further practice. Here we demonstrate the beneficial influence of sleep on auditory skill learning. Fifty-six subjects were randomly assigned to two groups, trained and tested on a pitch memory task three times across 24 h. The morning group was trained at 09.00 h, retested 12 h later that same day, and again after 12 h sleep. The evening group was trained at 21.00 h, retested 12 h immediately after sleep, and again 12 h later the next day. At retesting, both groups combined showed significant delayed learning only after sleep, but not across equivalent periods of wake, regardless of which came first. These data add to the growing literature describing sleep-dependent learning throughout sensory and motor domains.

Background and Aim. The role of sleep in the enhancement of motor skills has been been studied extensively in adults. We aimed to determine involvement of sleep and characteristics of spindles and slow waves in a motor skill in children. Hypothesis. We hypothesized sleep-dependence of skill enhancement and an association of interindividual differences in skill and sleep characteristics. Methods. 30 children (19 females, 10.7±0.8 years of age; mean±SD) performed finger sequence tapping tasks in a repeated-measures design spanning 4 days including 1 polysomnography night. Initial and delayed performance were assessed over 12 hours of wake; 12 hours with sleep; and 24 hours with wake and sleep. For the 12 hours with sleep, children were assigned to one of three conditions: modulation of slow waves and spindles was attempted using acoustic perturbation, and compared to yoked and no-sound control conditions. Analyses. Mixed effect regression models evaluated the association of sleep, its macrostructure and spindles and slow wave parameters with initial and delayed speed and accuracy. Results and Conclusions. Children enhance their accuracy only over an interval with sleep. Unlike previously reported in adults, children enhance their speed independent of sleep, a capacity that may to be lost in adulthood. Individual differences in the dominant frequency of spindles and slow waves were predictive for performance: children performed better if they had less slow spindles, more fast spindles and faster slow waves. On the other hand, overnight enhancement of accuracy was most pronounced in children with more slow spindles and slower slow waves, i.e. the ones with an initial lower performance. Associations of spindle and slow wave characteristics with initial performance may confound interpretation of their involvement in overnight enhancement. Slower frequencies of characteristic sleep events may mark slower learning and immaturity of networks involved in motor skills.

This Review article discusses in the context of learning and memory the function of sleep to earmark which daily event or information should be consolidated and which mundane information should be discarded, and how this 'memory triage' process is a selective and yet generalization process that can also bind features together in a non-congruous manner when they are recalled. The brain does not retain all the information it encodes in a day. Much is forgotten, and of those memories retained, their subsequent evolution can follow any of a number of pathways. Emerging data makes clear that sleep is a compelling candidate for performing many of these operations. But how does the sleeping brain know which information to preserve and which to forget? What should sleep do with that information it chooses to keep? For information that is retained, sleep can integrate it into existing memory networks, look for common patterns and distill overarching rules, or simply stabilize and strengthen the memory exactly as it was learned. We suggest such 'memory triage' lies at the heart of a sleep-dependent memory processing system that selects new information, in a discriminatory manner, and assimilates it into the brain's vast armamentarium of evolving knowledge, helping guide each organism through its own, unique life.

While a role for sleep in declarative memory processing is established, the qualitative nature of this consolidation benefit, and the physiological mechanisms mediating it, remain debated. Here, we investigate the impact of sleep physiology on characteristics of episodic memory using an item- (memory elements) and context- (contextual details associated with those elements) learning paradigm; the latter being especially dependent on the hippocampus. Following back-to-back encoding of two word lists, each associated with a different context, participants were assigned to either a Nap-group, who obtained a 120-min nap, or a No Nap-group. Six hours post-encoding, participants performed a recognition test involving item-memory and context-memory judgments. In contrast to item-memory, which demonstrated no between-group differences, a significant benefit in context-memory developed in the Nap-group, the extent of which correlated both with the amount of stage-2 NREM sleep and frontal fast sleep-spindles. Furthermore, a difference was observed on the basis of word-list order, with the sleep benefit and associated physiological correlations being selective for the second word-list, learned last (most proximal to sleep). These findings suggest that sleep may preferentially benefit contextual (hippocampal-dependent) aspects of memory, supported by sleep-spindle oscillations, and that the temporal order of initial learning differentially determines subsequent offline consolidation.

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

As critical as waking brain function is to cognition, an extensive literature now indicates that sleep supports equally important, different, yet complementary operations. This review will consider recent and emerging findings implicating sleep, and specific sleep-stage physiologies, in the modulation, regulation and even preparation of cognitive and emotional brain processes. First, evidence for the role of sleep in memory processing will be discussed, principally focusing on declarative memory. Second, at a neural level, several mechanistic models of sleep-dependent plasticity underlying these effects will be reviewed, with a synthesis of these features offered that may explain the ordered structure of sleep, and the orderly evolution of memory stages. Third, accumulating evidence for the role of sleep in associative memory processing will be discussed, suggesting that the long-term goal of sleep may not be the strengthening of individually memory items, but, instead, their abstracted assimilation into a schema of generalized knowledge. Forth, the newly emerging benefit of sleep in regulating emotional brain reactivity will be considered. Finally, and building on this latter topic, a novel hypothesis and framework of sleep-dependent affective brain processing will be proposed, culminating in testable predictions and translational implications for mood disorders.

Diekelmann and Born offer an elegant and convincing overview of evidence supporting sleep’s role in the consolidation of newly acquired memories1. Increasing awareness of memory stages that move beyond classical consolidation (e.g.2), a process concerned with the veridical preservation of stored information, highlights the internal contradictions of a system which, on the one hand, may seek to preserve memories in their original form, while on the other, allows them to evolve into more generalized representations of the world in which we live. While there is considerable evidence that slow-wave sleep (SWS) facilitates the consolidation and thus preservation of newly formed episodic memories3, emerging evidence suggests that sleep, and in some cases, rapid eye movement (REM) sleep, can play an important role in the extraction of generalized informational schemas from individual experiences4–6. This is an alternative view to that proposed by Diekelmann and Born 1, which examines systems- followed by synaptic-consolidation across the night. Here, we focus on the integrative stage of memory processing3, 7, beyond consolidation. Without implying that any of these stages is uniquely linked to a specific brain state, we review evidence for the proposal that sleep, and REM sleep in particular, supports three specific, but not mutually exclusive, forms of memory integration: 1) the unitization of recently acquired related items, 2) the assimilation of recently encoded items into networks of more remote items, and 3) the abstraction of generalizable rules from existing information stores, a process that leads to the construction of novel, higher-level schemas (Fig 1). Figure 1 Evolutionary stages of episodic memory processing

Cognitive neuroscience continues to build meaningful connections between affective behavior and human brain function. Within the biological sciences, a similar renaissance has taken place, focusing on the role of sleep in various neurocognitive processes and, most recently, on the interaction between sleep and emotional regulation. This review surveys an array of diverse findings across basic and clinical research domains, resulting in a convergent view of sleep-dependent emotional brain processing. On the basis of the unique neurobiology of sleep, the authors outline a model describing the overnight modulation of affective neural systems and the (re)processing of recent emotional experiences, both of which appear to redress the appropriate next-day reactivity of limbic and associated autonomic networks. Furthermore, a rapid eye movement (REM) sleep hypothesis of emotional-memory processing is proposed, the implications of which may provide brain-based insights into the association between sleep abnormalities and the initiation and maintenance of mood disturbances.

Molecular, cellular, and systems-level processes convert initial, labile memory representations into more permanent ones, available for continued reactivation and recall over extended periods of time. These processes of memory consolidation and reconsolidation are not all-or-none phenomena, but rather a continuing series of biological adjustments that enhance both the efficiency and utility of stored memories over time. In this chapter, we review the role of sleep in supporting these disparate but related processes.

Relational memory, the flexible ability to generalize across existing stores of information, is a fundamental property of human cognition. Little is known, however, about how and when this inferential knowledge emerges. Here, we test the hypothesis that human relational memory develops during offline time periods. Fifty-six participants initially learned five “premise pairs” (A>B, B>C, C>D, D>E, and E>F). Unknown to subjects, the pairs contained an embedded hierarchy (A>B>C>D>E>F). Following an offline delay of either 20 min, 12 hr (wake or sleep), or 24 hr, knowledge of the hierarchy was tested by examining inferential judgments for novel “inference pairs” (B>D, C>E, and B>E). Despite all groups achieving near-identical premise pair retention after the offline delay (all groups, >85%; the building blocks of the hierarchy), a striking dissociation was evident in the ability to make relational inference judgments: the 20-min group showed no evidence of inferential ability (52%), whereas the 12- and 24-hr groups displayed highly significant relational memory developments (inference ability of both groups, >75%; P < 0.001). Moreover, if the 12-hr period contained sleep, an additional boost to relational memory was seen for the most distant inferential judgment (the B>E pair; sleep = 93%, wake = 69%, P = 0.03). Interestingly, despite this increase in performance, the sleep benefit was not associated with an increase in subjective confidence for these judgments. Together, these findings demonstrate that human relational memory develops during offline time delays. Furthermore, sleep appears to preferentially facilitate this process by enhancing hierarchical memory binding, thereby allowing superior performance for the more distant inferential judgments, a benefit that may operate below the level of conscious awareness.

Although the functions of sleep remain largely unknown, one of the most exciting hypotheses is that sleep contributes importantly to processes of memory and brain plasticity. Over the past decade, a large body of work, spanning most of the neurosciences, has provided a substantive body of evidence supporting this role of sleep in what is becoming known as sleep-dependent memory processing. We review these findings, focusing specifically on the role of sleep in (a) memory encoding, (b) memory consolidation, (c) brain plasticity, and (d) memory reconsolidation; we finish with a summary of the field and its potential future directions.

We have previously presented a wealth of data refuting the proposal that memories are processed or consolidated in sleep. Our objections have been largely ignored, creating the impression that the hypothesized role for sleep in memory processing is an established fact rather than a highly controversial and unresolved issue. We briefly review the main arguments against a role for sleep in learning/memory.

Memory consolidation and reconsolidation reflect molecular, cellular and systems-level processes that convert labile memory representations into more permanent ones, available for continued reactivation and recall over extended periods of time. Here, we discuss the complexities of consolidation and reconsolidation, and suggest they should be viewed not as all-or-none phenomena, but as a continuing series of biological adjustments that enhance both the efficiency and the utility of stored memories over time and in response to changing needs of the organism. As such, consolidation and reconsolidation might be better thought of as memory organization and reorganization. A rapidly growing body of evidence suggests that many of these processes are optimally engaged during sleep.

Growing evidence suggests that sleep plays an important role in the process of procedural learning. Most recently, sleep has been implicated in the continued development of motor-skill learning following initial acquisition. However, the temporal evolution of motor learning before and after sleep, the effects of different training regimens, and the long-term development of motor learning across multiple nights of sleep remain unknown. Here, we report data for subjects trained and retested on a sequential finger-tapping task across multiple days. The findings demonstrate firstly that following initial training, small practice-dependent improvements are possible before, but not following the large practice-independent gains that develop across a night of sleep. Secondly, doubling the quantity of initial training does not alter the amount of subsequent sleep-dependent learning that develops overnight. Thirdly, the amount of sleep-dependent learning does not correlate with the amount of practice-dependent learning achieved during training, suggesting the existence of two discrete motor-learning processes. Finally, whereas the majority of sleep-dependent motor-skill learning develops during the first night of sleep following training, additional nights of sleep still offer continued improvements.

Improvement in motor skill performance is known to continue for at least 24 hr following training, yet the relative contributions of time spent awake and asleep are unknown. Here we provide evidence that a night of sleep results in a 20% increase in motor speed without loss of accuracy, while an equivalent period of time during wake provides no significant benefit. Furthermore, a significant correlation exists between the improved performance overnight and the amount of stage 2 NREM sleep, particularly late in the night. This finding of sleep-dependent motor skill improvement may have important implications for the efficient learning of all skilled actions in humans.