Eye movements during phasic versus tonic rapid eye movement sleep are biomarkers of dissociable electroencephalogram processes for the consolidation of novel problem-solving skills.

The hallmark eye movement (EM) bursts that occur during rapid eye movement (REM) sleep are markers of consolidation for procedural memory involving novel cognitive strategies and problem-solving skills. Examination of the brain activity associated with EMs during REM sleep might elucidate the processes involved in memory consolidation, and may uncover the functional significance of REM sleep and EMs themselves. Participants performed a REM-dependent, novel procedural problem-solving task (i.e. the Tower of Hanoi; ToH) before and after intervals of either overnight sleep (n = 20) or a daytime 8-hour wake period (n = 20). In addition, event-related spectral perturbation of the electroencephalogram (EEG) time-locked to EMs occurring either in bursts (i.e. phasic REM), or in isolation (i.e. tonic REM), were compared to sleep on a non-learning control night. ToH improvement was greater following sleep compared to wakefulness. During sleep, prefrontal theta (~2-8 Hz) and central-parietal-occipital sensorimotor rhythm (SMR) activity (~8-16 Hz) time-locked to EMs, were greater on the ToH night versus control night, and during phasic REM sleep, were both positively correlated with overnight memory improvements. Furthermore, SMR power during tonic REM increased significantly from the control night to ToH night, but was relatively stable from night to night during phasic REM. These results suggest that EMs are markers of learning-related increases in theta and SMR during phasic and tonic REM sleep. Phasic and tonic REM sleep may be functionally distinct in terms of their contribution to procedural memory consolidation.

Sleep spindles and slow waves are physiological markers for age-related changes in gray matter in brain regions supporting problem-solving skills.

As we age, the added benefit of sleep for memory consolidation is lost. One of the hallmark age-related changes in sleep is the reduction of sleep spindles and slow waves. Gray matter neurodegeneration is related to both age-related changes in sleep and age-related changes in memory, including memory for problem-solving skills. Here, we investigated whether spindles and slow waves might serve as biological markers for neurodegeneration of gray matter and for the related memory consolidation deficits in older adults. Forty healthy young adults (20-35 yr) and 30 healthy older adults (60-85 yr) were assigned to either nap or wake conditions. Participants were trained on the Tower of Hanoi in the morning, followed by either a 90-min nap opportunity or period of wakefulness, and were retested afterward. We found that age-related changes in sleep spindles and slow waves were differentially related to gray matter intensity in young and older adults in brain regions that support sleep-dependent memory consolidation for problem-solving skills. Specifically, we found that spindles were related to gray matter in neocortical areas (e.g., somatosensory and parietal cortex), and slow waves were related to gray matter in the anterior cingulate, hippocampus, and caudate, all areas known to support problem-solving skills. These results suggest that both sleep spindles and slow waves may serve as biological markers of age-related neurodegeneration of gray matter and the associated reduced benefit of sleep for memory consolidation in older adults.

Brain activations time locked to slow wave-coupled sleep spindles correlates with intellectual abilities.

Sleep spindles (SP) are one of the few known electrophysiological neuronal biomarkers of interindividual differences in cognitive abilities and aptitudes. Recent simultaneous electroencephalography with functional magnetic resonance imaging (EEG-fMRI) studies suggest that the magnitude of the activation of brain regions recruited during spontaneous spindle events is specifically related to Reasoning abilities. However, it is not known if the relationship with cognitive abilities differs between uncoupled spindles, uncoupled slow waves (SW), and coupled SW-SP complexes, nor have the functional-neuroanatomical substrates that support this relationship been identified. Here, we investigated the functional significance of activation of brain areas recruited during SW-coupled spindles, uncoupled spindles, and uncoupled slow waves. We hypothesize that brain activations time locked to SW-coupled spindle complexes will be primarily associated to Reasoning abilities, especially in subcortical areas. Our results provide direct evidence that the relationship between Reasoning abilities and sleep spindles depends on spindle coupling status. Specifically, we found that the putamen and thalamus, recruited during coupled SW-SP events were positively correlated with Reasoning abilities. In addition, we found a negative association between Reasoning abilities and hippocampal activation time-locked to uncoupled SWs that might reflect a refractory mechanism in the absence of new, intensive hippocampal-dependent memory processing.

Age-related differences in problem-solving skills: Reduced benefit of sleep for memory trace consolidation.

We investigated the behavioural and neuronal functional consequences of age-related differences in sleep for gaining insight into novel cognitive strategies. Forty healthy young adults (20-35 years), and twenty-nine healthy older adults (60-85 years) were assigned to either nap or wake conditions. Participants were trained on the Tower of Hanoi in the AM, followed by either a 90-minute nap opportunity or period of wakefulness, and were retested afterward. Functional magnetic resonance imaging scans examined differences in brain activation from training to retest in young versus older adults as a function of sleep. Sleep enhanced performance and transformed the memory trace in young adults via hippocampal-neocortical transfer, but not older adults. This is consistent with the notion that as the consolidation of a newly formed memory trace progresses, the hippocampus becomes less involved; especially so when sleep occurs during that time. These results demonstrate a critical role for sleep in supporting problem-solving skills and suggest that the benefit of sleep for consolidation of these skills is reduced with age.

Functional differences in cerebral activation between slow wave-coupled and uncoupled sleep spindles.

Spindles are often temporally coupled to slow waves (SW). These SW-spindle complexes have been implicated in memory consolidation that involves transfer of information from the hippocampus to the neocortex. However, spindles and SW, which are characteristic of NREM sleep, can occur as part of this complex, or in isolation. It is not clear whether dissociable parts of the brain are recruited when coupled to SW vs. when spindles or SW occur in isolation. Here, we tested differences in cerebral activation time-locked to uncoupled spindles, uncoupled SW and coupled SW-spindle complexes using simultaneous EEG-fMRI. Consistent with the "active system model," we hypothesized that brain activations time-locked to coupled SW-spindles would preferentially occur in brain areas known to be critical for sleep-dependent memory consolidation. Our results show that coupled spindles and uncoupled spindles recruit distinct parts of the brain. Specifically, we found that hippocampal activation during sleep is not uniquely related to spindles. Rather, this process is primarily driven by SWs and SW-spindle coupling. In addition, we show that SW-spindle coupling is critical in the activation of the putamen. Importantly, SW-spindle coupling specifically recruited frontal areas in comparison to uncoupled spindles, which may be critical for the hippocampal-neocortical dialogue that preferentially occurs during sleep.

Reversed and increased functional connectivity in non-REM sleep suggests an altered rather than reduced state of consciousness relative to wake.

Sleep resting state network (RSN) functional connectivity (FC) is poorly understood, particularly for rapid eye movement (REM), and in non-sleep deprived subjects. REM and non-REM (NREM) sleep involve competing drives; towards hypersynchronous cortical oscillations in NREM; and towards wake-like desynchronized oscillations in REM. This study employed simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) to explore whether sleep RSN FC reflects these opposing drives. As hypothesized, this was confirmed for the majority of functional connections modulated by sleep. Further, changes were directional: e.g., positive wake correlations trended towards negative correlations in NREM and back towards positive correlations in REM. Moreover, the majority did not merely reduce magnitude, but actually either reversed and strengthened in the opposite direction, or increased in magnitude during NREM. This finding supports the notion that NREM is best expressed as having altered, rather than reduced FC. Further, as many of these functional connections comprised "higher-order" RSNs (which have been previously linked to cognition and consciousness), such as the default mode network, this finding is suggestive of possibly concomitant alterations to cognition and consciousness.

Sleep, Orexin and Cognition.

Orexins regulate a wide variety of biological functions, most notably the sleep-wake cycle, reward and stress processing, alertness, vigilance, and cognitive functioning. Alterations of central and peripheral orexin levels are linked to conditions such as narcolepsy, anorexia nervosa, age-related cognitive decline, and neurodegenerative disease. Preliminary studies suggest that orexin mimetics can safely promote the wake signal via orexin agonism during the day and that orexin receptor antagonists can promote the sleep signal during the night. Thus, novel orexin therapies have the potential to either improve memory, cognition, and daytime performance directly or indirectly, through promotion of good sleep. The full scope of the therapeutic potential of orexin therapies remains to be elucidated.

Selective serotonin reuptake inhibitor use is associated with worse sleep-related breathing disturbances in individuals with depressive disorders and sleep complaints: a retrospective study.

STUDY OBJECTIVES: The effects of serotonergic agents on respiration neuromodulation may vary according to differences in the serotonin system, such as those linked to depression. This study investigated how sleep-related respiratory disturbances relate to depression and the use of medications commonly prescribed for depression. METHODS: Retrospective polysomnography was collated for all 363 individuals who met selection criteria out of 2,528 consecutive individuals referred to a specialized sleep clinic (Ottawa, Canada) between 2006 and 2016. The apnea-hypopnea index (AHI), oxygen saturation nadir, and oxygen desaturation index during REM and NREM sleep were analyzed using mixed analyses of covariance comparing 3 main groups: (1) medicated individuals with depressive disorders (antidepressant group; subdivided into the selective serotonin reuptake inhibitor and norepinephrine-dopamine reuptake inhibitor subgroups), (2) non-medicated individuals with depressive disorders (non-medicated group), and (3) mentally healthy control patients (control group). RESULTS: Individuals with depressive disorders (on antidepressants or not) had significantly higher AHIs compared to control patients (both P ≤ .007). The antidepressant group had a lower NREM sleep oxygen saturation nadir and a higher NREM sleep oxygen desaturation index than the control and non-medicated groups (all P ≤ .009). Within individuals with depressive disorders, independent of depression severity, the selective serotonin reuptake inhibitor group had a lower oxygen saturation nadir and a higher oxygen desaturation index during NREM sleep than the norepinephrine-dopamine reuptake inhibitor (both P ≤ .045) and non-medicated groups (both P < .001) and a higher NREM sleep AHI than the non-medicated group (P = .014). CONCLUSIONS: These findings suggest that the use of selective serotonin reuptake inhibitors may be associated with impaired breathing and worse nocturnal oxygen saturation in individuals with depressive disorders and sleep complaints, but this needs to be confirmed by prospective studies.

24-h polysomnographic recordings and electrophysiological spectral analyses from a cohort of patients with chronic disorders of consciousness.

Fourteen patients with severe brain injuries and chronic disorders of consciousness underwent polysomnographic recordings for a 24-h period. Their electrophysiological data were scored using a modified sleep staging system employed in a previous study of similar patients (J Head Trauma Rehabil 30:334-346, 2015). In addition to sleep scoring, the patients' data were compared with a sample of approximately age-matched healthy volunteers in the spectral domain. All patients demonstrated some form of a sleep-wake cycle; however, the integrity of normal sleep features was remarkably heterogenous across individuals, and in some cases, sleep was significantly impoverished. In three patients, these cycles were biphasic and comprised of only alternating periods of wakefulness and sleep-like electrophysiological activity. Two patients demonstrated a sleep-wake cycle that included all sleep stages aside from non-REM stage 3, and another two patients demonstrated a sleep-wake cycle that included all sleep stages aside from REM sleep. The remaining seven patients, which included patients diagnosed as being in a minimally conscious state and patients diagnosed as being in a vegetative state (unresponsive wakefulness syndrome), demonstrated full sleep architecture, including k-complexes, REMs, and slow wave sleep. However, three of the patients with full sleep architecture did not generate sleep spindles. Altogether, these findings highlight the heterogeneity of brain function among patients with disorders of consciousness, regardless of their diagnostic category. Polysomnography is a useful tool to complement other behavioural and physiological assessments that characterize the abilities of each patient.

Autonomic Modulation of Cardiac Activity Across Levels of Sleep Depth in Individuals With Depression and Sleep Complaints.

OBJECTIVE: We assessed mean heart rate (HR) and HR variability (HRV) across wake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep, and across varying levels of NREM sleep depth in individuals with depression and sleep complaints. METHODS: Retrospective polysomnographic data were obtained for 25 individuals diagnosed as having depression (84% female; mean age = 33.8 ± 12.2 years) and 31 mentally healthy controls (58.1% female; mean age = 37.2 ± 12.4 years). All were free of psychotropic and cardiovascular medication, cardiovascular disease, and sleep-related breathing disorders. HR and time-domain HRV parameters were computed on 30-second electrocardiography segments and averaged across the night for each stage of sleep and wake. RESULTS: Compared with the control group, the depression group had higher HR across wake, REM, and all levels of NREM depth (F(1,51) = 6.3, p = .015). Significant group by sleep stage interactions were found for HRV parameters: SD of normal-to-normal intervals (SDNN; F(2.1,107.7) = 4.4, p = .014) and root mean square differences of successive R-R intervals (RMSSD; F(2.2,113.5) = 3.2, p = .041). No significant group difference was found for SDNN or RMSSD during wake (all, p ≥ .32). However, compared with the control group, the depression group had significantly lower SDNN in REM (p = .040) and all NREM stages (all p ≤ .045), and lower RMSSD during NREM 2 (p = .033) and NREM 3 (p = .034). CONCLUSIONS: This study suggests that the abnormalities in autonomic cardiac regulation associated with depression and sleep problems are more prominent during sleep, especially NREM sleep, than during wake. This may be due to abnormalities in parasympathetic modulation of cardiac activity.

Sleep Spindle-dependent Functional Connectivity Correlates with Cognitive Abilities.

EEG studies have shown that interindividual differences in the electrophysiological properties of sleep spindles (e.g., density, amplitude, duration) are highly correlated with trait-like "reasoning" abilities (i.e., "fluid intelligence"; problem-solving skills; the ability to employ logic or identify complex patterns), but not interindividual differences in STM or "verbal" intellectual abilities. Previous simultaneous EEG-fMRI studies revealed brain activations time-locked to spindles. Our group has recently demonstrated that the extent of activation in a subset of these regions was related to interindividual differences in reasoning intellectual abilities, specifically. However, spindles reflect communication between spatially distant and functionally distinct brain areas. The functional communication among brain regions related to spindles and their relationship to reasoning abilities have yet to be investigated. Using simultaneous EEG-fMRI sleep recordings and psychophysiological interaction analysis, we identified spindle-related functional communication among brain regions in the thalamo-cortical-BG system, the salience network, and the default mode network. Furthermore, the extent of the functional connectivity of the cortical-striatal circuitry and the thalamo-cortical circuitry was specifically related to reasoning abilities but was unrelated to STM or verbal abilities, thus suggesting that individuals with higher fluid intelligence have stronger functional coupling among these brain areas during spontaneous spindle events. This may serve as a first step in further understanding the function of sleep spindles and the brain network functional communication, which support the capacity for fluid intelligence.

Using heart rate profiles during sleep as a biomarker of depression.

BACKGROUND: Abnormalities in heart rate during sleep linked to impaired neuro-cardiac modulation may provide new information about physiological sleep signatures of depression. This study assessed the validity of an algorithm using patterns of heart rate changes during sleep to discriminate between individuals with depression and healthy controls. METHODS: A heart rate profiling algorithm was modeled using machine-learning based on 1203 polysomnograms from individuals with depression referred to a sleep clinic for the assessment of sleep abnormalities, including insomnia, excessive daytime fatigue, and sleep-related breathing disturbances (n = 664) and mentally healthy controls (n = 529). The final algorithm was tested on a distinct sample (n = 174) to categorize each individual as depressed or not depressed. The resulting categorizations were compared to medical record diagnoses. RESULTS: The algorithm had an overall classification accuracy of 79.9% [sensitivity: 82.8, 95% CI (0.73-0.89), specificity: 77.0, 95% CI (0.67-0.85)]. The algorithm remained highly sensitive across subgroups stratified by age, sex, depression severity, comorbid psychiatric illness, cardiovascular disease, and smoking status. CONCLUSIONS: Sleep-derived heart rate patterns could act as an objective biomarker of depression, at least when it co-occurs with sleep disturbances, and may serve as a complimentary objective diagnostic tool. These findings highlight the extent to which some autonomic functions are impaired in individuals with depression, which warrants further investigation about potential underlying mechanisms.

Brain Activation Time-Locked to Sleep Spindles Associated With Human Cognitive Abilities.

Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies have revealed brain activations time-locked to spindles. Yet, the functional significance of these spindle-related brain activations is not understood. EEG studies have shown that inter-individual differences in the electrophysiological characteristics of spindles (e.g., density, amplitude, duration) are highly correlated with "Reasoning" abilities (i.e., "fluid intelligence"; problem solving skills, the ability to employ logic, identify complex patterns), but not short-term memory (STM) or verbal abilities. Spindle-dependent reactivation of brain areas recruited during new learning suggests night-to-night variations reflect offline memory processing. However, the functional significance of stable, trait-like inter-individual differences in brain activations recruited during spindle events is unknown. Using EEG-fMRI sleep recordings, we found that a subset of brain activations time-locked to spindles were specifically related to Reasoning abilities but were unrelated to STM or verbal abilities. Thus, suggesting that individuals with higher fluid intelligence have greater activation of brain regions recruited during spontaneous spindle events. This may serve as a first step to further understand the function of sleep spindles and the brain activity which supports the capacity for Reasoning.

Sleep architecture in adolescents hospitalized during a suicidal crisis.

OBJECTIVE/BACKGROUND: Rates of suicide attempts in Canadian youths are concerning. Adolescence is a sensitive period for the emergence of both sleep and mood problems, two major risk factors for suicidality. This naturalistic study aimed to define the sleep profile of adolescents under the combined influence of suicidality, depression and pharmacotherapy during hospitalization for a suicidal crisis. PATIENTS/METHODS: Seventeen suicidal adolescents (15.0 + 1.2years, 82% females) with major depression were recruited from a Canadian pedopsychiatric inpatient unit. Seventeen non-depressed adolescents were retrospectively collated from another database (15.0 + 1.1years, 83% females). None of the participants had a history of sleep disorders or significant medical conditions. RESULTS: Compared to controls, suicidal adolescents had a longer sleep onset latency (Z = -4.5, p < 0.001), longer REM latency (Z = -3.2, p = 0.001), higher percentage of NREM1 sleep t(33) = -2.6, p = 0.020), and higher REM density (Z = -2.8, p = 0.004) than controls. Higher REM density correlated with higher CDI-II scores (r = 0.55, p = 0.27) A significant interaction indicated that the two groups had similar NREM3 percentages in the first two-thirds of the night, but that the suicidal group had significantly lower NREM3 percentage than the controls in the last third of the night (F(2,66) = 3.4, p = 0.041). CONCLUSIONS: Significant sleep abnormalities were observed during hospitalization for a suicidal crisis in a sample of depressed and mostly medicated adolescents. This included sleep initiation and REM sleep latency abnormalities, shallower sleep and high REM density. Future studies should decipher the relative effects of depression, suicidality and medication on sleep. These findings stress the need to address sleep disturbances in the management of suicidality in adolescents.

Toward a complete taxonomy of resting state networks across wakefulness and sleep: an assessment of spatially distinct resting state networks using independent component analysis.

Resting state network (RSN) functional connectivity (FC) has been investigated under a wealth of different healthy and compromised conditions. Such investigations are often dependent on the defined spatial boundaries and nodes of so-called canonical RSNs, themselves the product of extensive deliberations over distinctions between functional magnetic resonance imaging (fMRI) noise and neural signal, specifically in the context of the healthy waking state. However, a similar unbiased cataloging of noise and networks remains to be done in other states, particularly sleep, a healthy alternate mode of the brain that supports distinct operations from wakefulness, such as dreaming and memory consolidation. The purpose of this study was to explicitly test the hypothesis that there are RSNs unique to sleep. Simultaneous electroencephalography (EEG) and fMRI was used to record brain activity of non-sleep-deprived participants. Independent component analysis was performed on both rapid eye movement (REM; N = 7) and non-REM sleep stage fMRI data (non-REM2; N = 28, non-REM3; N = 11), with the resulting components spatially correlated with the canonical RSNs, for the purpose of identifying spatially distinct RSNs. Surprisingly, all low-correlation components were positively identified as noise, and all high-correlation components comprised the canonical set of RSNs typically observed in wake, indicating that sleep is supported by much the same RSN architecture as wakefulness, despite the unique operations performed during sleep. This further indicates that the implicit assumptions of prior studies, i.e. that the canonical RSNs apply to sleep FC analysis, are valid and have not overlooked sleep-specific RSNs.

Sustained vigilance is negatively affected by mild and acute sleep loss reflected by reduced capacity for decision making, motor preparation, and execution.

Study Objectives: The behavioral and cognitive consequences of severe sleep deprivation are well understood. Surprisingly, relatively little is known about the neural correlates of mild and acute sleep restriction on tasks that require sustained vigilance for prolonged periods of time during the day. Methods and Results: Event-related potential (ERP) paradigms can reveal insight into the neural correlates underlying visual processing and behavioral responding that is impaired with reduced alertness, as a consequence of sleep loss. Here, we investigated the impact of reduced vigilance following at-home mild sleep restriction to better understand the associated behavioral consequences and changes in information processing revealed by ERPs. As expected, vigilance was reduced (e.g. increased lapses and response slowing) that increased over the course of the experiment in the "sleep restricted" (5 hr sleep) compared with the "sleep-extension" (9 hr sleep) condition. Corresponding to these lapses, we found decreased positivity of visually evoked potentials in the Sleep Restriction vs. Sleep Extension condition emerging from 316 to 449 ms, maximal over parietal/occipital cortex. We also investigated electrophysiological signs of motor-related processing by comparing lateralized readiness potentials (LRPs) and found reduced positivity of LRPs in the Sleep Restriction vs. Sleep Extension condition at 70-40 ms before, and 115-158 ms after a response was made. Conclusions: These results suggest that even a single night of mild sleep restriction can negatively affect vigilance, reflected by reduced processing capacity for decision making, and dulls motor preparation and execution.

A Novel Approach to Dream Content Analysis Reveals Links Between Learning-Related Dream Incorporation and Cognitive Abilities.

Can dreams reveal insight into our cognitive abilities and aptitudes (i.e., "human intelligence")? The relationship between dream production and trait-like cognitive abilities is the foundation of several long-standing theories on the neurocognitive and cognitive-psychological basis of dreaming. However, direct experimental evidence is sparse and remains contentious. On the other hand, recent research has provided compelling evidence demonstrating a link between dream content and new learning, suggesting that dreams reflect memory processing during sleep. It remains to be investigated whether the extent of learning-related dream incorporation (i.e., the semantic similarity between waking experiences and dream content) is related to inter-individual differences in cognitive abilities. The relationship between pre-post sleep memory performance improvements and learning-related dream incorporation was investigated (N = 24) to determine if this relationship could be explained by inter-individual differences in intellectual abilities (e.g., reasoning, short term memory (STM), and verbal abilities). The extent of dream incorporation using a novel and objective method of dream content analysis, employed a computational linguistic approach to measure the semantic relatedness between verbal reports describing the experience on a spatial (e.g., maze navigation) or a motor memory task (e.g., tennis simulator) with subsequent hypnagogic reverie dream reports and waking "daydream" reports, obtained during a daytime nap opportunity. Consistent with previous studies, the extent to which something new was learned was related (r = 0.47) to how richly these novel experiences were incorporated into the content of dreams. This was significant for early (the first 4 dream reports) but not late dreams (the last 4 dream reports). Notably, here, we show for the first time that the extent of this incorporation for early dreams was related (r = 0.41) to inter-individual differences in reasoning abilities. On the other hand, late dream incorporation was related (r = 0.46) to inter-individual differences in verbal abilities. There was no relationship between performance improvements and intellectual abilities, and thus, inter-individual differences in cognitive abilities did not mediate the relationship between performance improvements and dream incorporation; suggesting a direct relationship between reasoning abilities and dream incorporation. This study provides the first evidence that learning-related dream production is related to inter-individual differences in cognitive abilities.

Does sleep facilitate the consolidation of allocentric or egocentric representations of implicitly learned visual-motor sequence learning?

Sleep facilitates the consolidation (i.e., enhancement) of simple, explicit (i.e., conscious) motor sequence learning (MSL). MSL can be dissociated into egocentric (i.e., motor) or allocentric (i.e., spatial) frames of reference. The consolidation of the allocentric memory representation is sleep-dependent, whereas the egocentric consolidation process is independent of sleep or wake for explicit MSL. However, it remains unclear the extent to which sleep contributes to the consolidation of implicit (i.e., unconscious) MSL, nor is it known what aspects of the memory representation (egocentric, allocentric) are consolidated by sleep. Here, we investigated the extent to which sleep is involved in consolidating implicit MSL, specifically, whether the egocentric or the allocentric cognitive representations of a learned sequence are enhanced by sleep, and whether these changes support the development of explicit sequence knowledge across sleep but not wake. Our results indicate that egocentric and allocentric representations can be behaviorally dissociated for implicit MSL. Neither representation was preferentially enhanced across sleep nor were developments of explicit awareness observed. However, after a 1-wk interval performance enhancement was observed in the egocentric representation. Taken together, these results suggest that like explicit MSL, implicit MSL has dissociable allocentric and egocentric representations, but unlike explicit sequence learning, implicit egocentric and allocentric memory consolidation is independent of sleep, and the time-course of consolidation differs significantly.

Sleep-dependent motor sequence memory consolidation in individuals with periodic limb movements.

Periodic limb movements (PLMs) during sleep increase with age and are associated with striatal neurodegeneration and dopamine deficiency. Limb movements are often associated with disruptions to non-rapid eye movement (NREM) sleep. Motor skill memory consolidation recruits the striatum, and learning-dependent striatal activation is associated with NREM sleep. Therefore, we investigated whether de novo individuals who significantly experience elevated levels of PLMs but have not been formally diagnosed with periodic limb movement disorder had learning and sleep-related memory deficits and whether these deficits were related to sleep quality and symptom severity. In total, 14 adults with significantly elevated PLMs (PLM condition), 15 age-matched controls (CTRL), and 14 age-matched "disturbed" sleep (through induced leg movements) controls (CTRL-ES) participated. The participants were trained (PM) and retested (AM) on procedural motor sequence learning (MSL) and declarative paired associates memory tasks. Baseline sleep quality was significantly worse in PLM than in CTRL. Despite the continued presence of PLMs in the PLM condition on the experimental night, remarkably, sleep quality improved and arousals decreased, vs. baseline, and did not differ from CTRL. MSL was significantly slower in the PLM condition than in CTRL at training but surprisingly exhibited overnight performance gains, which correlated with reduced arousals. As predicted, CTRL but not CTRL-ES had overnight gains in MSL. Taken together, this suggests that in the PLM condition, sleep quality was normalized following MSL, where they derived the same benefit of sleep to procedural memory consolidation as in CTRL. Sleep did not benefit declarative memory. Although preliminary, these results suggest that MSL in individuals with PLMs may provide a benefit to sleep, which in turn may benefit memory consolidation.

Sleep Spindles and Intellectual Ability: Epiphenomenon or Directly Related?

Sleep spindles-short, phasic, oscillatory bursts of activity that characterize non-rapid eye movement sleep-are one of the only electrophysiological oscillations identified as a biological marker of human intelligence (e.g., cognitive abilities commonly assessed using intelligence quotient tests). However, spindles are also important for sleep maintenance and are modulated by circadian factors. Thus, the possibility remains that the relationship between spindles and intelligence quotient may be an epiphenomenon of a putative relationship between good quality sleep and cognitive ability or perhaps modulated by circadian factors such as morningness-eveningness tendencies. We sought to ascertain whether spindles are directly or indirectly related to cognitive abilities using mediation analysis. Here, we show that fast (13.5-16 Hz) parietal but not slow (11-13.5 Hz) frontal spindles in both non-rapid eye movement stage 2 sleep and slow wave sleep are directly related to reasoning abilities (i.e., cognitive abilities that support "fluid intelligence," such as the capacity to identify complex patterns and relationships and the use of logic to solve novel problems) but not verbal abilities (i.e., cognitive abilities that support "crystalized intelligence"; accumulated knowledge and experience) or cognitive abilities that support STM (i.e., the capacity to briefly maintain information in an available state). The relationship between fast spindles and reasoning abilities is independent of the indicators of sleep maintenance and circadian chronotype, thus suggesting that spindles are indeed a biological marker of cognitive abilities and can serve as a window to further explore the physiological and biological substrates that give rise to human intelligence.