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The sleep homeostatic process in adults is moderately stable over time and unique to an individual. Work in transgenic mice has suggested a role of genes in sleep homeostasis. The current study quantified the genetic contribution to sleep homeostasis in adolescence. We use slow wave energy (SWE) as a metric for sleep pressure dissipation during sleep. This measure reflects both sleep intensity and duration. High‐density (58 derivations) sleep electroencephalogram (EEG) was recorded in 14 monozygotic and 12 dizygotic adolescent twin pairs (mean age = 13.2 years; standard deviation [SD] = 1.1; 20 females). SWE at the end of sleep was quantified as the cumulative delta power (1–4.6 Hz) over the night. We also examined the time constant of the decay and the level of slow wave activity (SWA) at the beginning of the sleep episode. Structural equation modelling was used to quantify the amount of variance in SWE and the dissipation of sleep pressure due to genes. We found that most (mean = 76% across EEG derivations) of the variance in SWE was due to genes. In contrast, genes had a small (mean = 33%) influence on the rate of dissipation of sleep pressure, and this measure was largely (mean = 67%) driven by environmental factors unique to each twin. Our results show that the amount of dissipated sleep pressure is largely under genetic control; however, the rate of sleep pressure dissipation is largely due to unique environmental factors. Our findings are in line with research in animals and suggest that the heritability of the rate of sleep pressure dissipation is limited. [ABSTRACT FROM AUTHOR]

Depression and sleep disturbances are commonly seen non-motor symptoms in patients with Parkinson's disease (PD). This study used polysomnography to examine the relationship between mild-moderate depression in PD and sleep characteristics, particularly slow wave activities (SWA). 59 PD patients were split into two groups: nd-PD (n = 27) (patients with PD without depression) and d-PD (n = 32) (patients with PD with mild-moderate depression). Their clinical features, polysomnography parameters, and demographics were evaluated. Early and late sleep SWA spectrum densities and overnight SWA decline in different brain regions were particularly analyzed. Non-rapid eye movement 3 (N3) sleep duration and percentage were greater in the d-PD group. N3 percentage was linked to depression (p = 0.014). During late sleep, higher SWA (0.5–4Hz) in the frontal and central regions, higher low-SWA (0.5–2Hz) in the whole brain, central and occipital regions, and higher high-SWA (2–4Hz) in the frontal region was observed in the d-PD group. During early sleep, there was also higher low-SWA (0.5–2Hz) in the occipital region. Patients in d-PD group exhibited reduced overnight high-SWA (2–4Hz) decline (Δhigh-SWA) in the whole brain and occipital regions. Δhigh-SWA(2–4Hz) in the occipital region were associated with depression (p = 0.049). PD patients with mild-moderate depression have impaired slow wave sleep, exhibiting as increased N3 sleep, SWA, and reduced overnight SWA decline. This implies that synaptic strength reduction during sleep and impaired synaptic homeostasis regulation may be associated with depression in PD. Reduced overnight high-SWA decline in the occipital region may serve as a novel electrophysiological biomarker for indicating depression in PD. • PD patients with depression have impaired slow wave sleep and reduced overnight SWA decline. • Impaired synaptic homeostasis regulation may be associated with depression in PD. • Reduced overnight high-SWA decline may serve as a biomarker for indicating depression in PD. [ABSTRACT FROM AUTHOR]

Summary: Acute exercise has been shown to affect long‐term memory and sleep. However, it is unclear whether exercise‐induced changes in sleep architecture are associated with enhanced memory. Recently, it has been shown that exercise followed by a nap improved declarative memory. Whether these effects transfer to night sleep and other memory domains has not yet been studied. Here, we investigate the influence of exercise on nocturnal sleep architecture and associations with sleep‐dependent procedural and declarative memory consolidation. Nineteen subjects (23.68 ± 3.97 years) were tested in a balanced cross‐over design. In two evening sessions, participants either exercised (high‐intensity interval training) or rested immediately after encoding two memory tasks: (1) a finger tapping task and (2) a paired‐associate learning task. Subsequent nocturnal sleep was recorded by polysomnography. Retrieval was conducted the following morning. High‐intensity interval training lead to an increased declarative memory retention (p = 0.047, d = 0.40) along with a decrease in REM sleep (p = 0.012, d = 0.75). Neither procedural memory nor NREM sleep were significantly affected. Exercise‐induced changes in N2 showed a positive correlation with procedural memory retention which did not withstand multiple comparison correction. Exploratory analyses on sleep spindles and slow wave activity did not reveal significant effects. The present findings suggest an exercise‐induced enhancement of declarative memory which aligns with changes in nocturnal sleep architecture. This gives additional support for the idea of a potential link between exercise‐induced sleep modifications and memory formation which requires further investigation in larger scaled studies. [ABSTRACT FROM AUTHOR]

Study objectivesAdolescence is characterized by significant brain development, accompanied by changes in sleep timing and architecture. It also is a period of profound psychosocial changes, including the initiation of alcohol use; however, it is unknown how alcohol use affects sleep architecture in the context of adolescent development. We tracked developmental changes in polysomnographic (PSG) and electroencephalographic (EEG) sleep measures and their relationship with emergent alcohol use in adolescents considering confounding effects (e.g. cannabis use).MethodsAdolescents (n = 94, 43% female, age: 12-21 years) in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study had annual laboratory PSG recordings across 4-years. Participants were no/low drinkers at baseline.ResultsLinear mixed effect models showed developmental changes in sleep macrostructure and EEG, including a decrease in slow wave sleep and slow wave (delta) EEG activity with advancing age. Emergent moderate/heavy alcohol use across three follow-up years was associated with a decline in percentage rapid eye movement (REM) sleep over time, a longer sleep onset latency (SOL) and shorter total sleep time (TST) in older adolescents, and lower non-REM delta and theta power in males.ConclusionsThese longitudinal data show substantial developmental changes in sleep architecture. Emergent alcohol use during this period was associated with altered sleep continuity, architecture, and EEG measures, with some effects dependent on age and sex. These effects, in part, could be attributed to the effects of alcohol on underlying brain maturation processes involved in sleep-wake regulation.

Research on slow-wave sleep (SWS) began almost a century ago, not long after the discovery of electroencephalography. From maintaining homeostasis to memory function, the pivotal role of SWS in health has been established. The elucidation of its mechanisms and functions is directly related to the fundamental question of why people sleep. This comprehensive review first summarizes the basic science of SWS from anatomical and physiological aspects. It describes the fundamental mechanisms and functions of SWS, including hormonal regulation, developmental changes in SWS across the lifespan, and associations between SWS and optimal physical, psychological, and cognitive functions. Next, the relationship between SWS and physical and mental disorders, for which increasing knowledge has accumulated in recent years, is discussed from both research and clinical perspectives. Conditions such as memory impairment, sleep-disordered breathing, neurodevelopmental disorders, and various psychiatric disorders are of concern. The relationship between SWS and the glymphatic system, which is responsible for waste clearance in the brain, has also been explored, highlighting the potential neuroprotective role of SWS. Finally, we discuss the future direction of the field regarding whether interventions in SWS can improve health. We also address the problem of the inconsistent definitions of SWS, slow-wave activity, and slow oscillations. This review emphasizes the importance of discussing SWS from both macro- and microarchitectural perspectives and highlights its potential clinical and research impacts. By reviewing these aspects, we aim to contribute to a deeper understanding of SWS and the future development of this research field. [ABSTRACT FROM AUTHOR]

During preadolescence the sleep electroencephalography undergoes massive qualitative and quantitative modifications. Despite these relevant age-related peculiarities, the specific EEG pattern of the wake-sleep transition in preadolescence has not been exhaustively described. The aim of the present study is to characterize regional and temporal electrophysiological features of the sleep onset (SO) process in a group of 23 preadolescents (9–14 years) and to compare the topographical pattern of slow wave activity and delta/beta ratio of preadolescents with the EEG pattern of young adults. Results showed in preadolescence the same dynamics known for adults, but with peculiarities in the delta and beta activity, likely associated with developmental cerebral modifications: the delta power showed a widespread increase during the SO with central maxima, and the lower bins of the beta activity showed a power increase after SO. Compared to adults, preadolescents during the SO exhibited higher delta power only in the slowest bins of the band: before SO slow delta activity was higher in prefrontal, frontal and occipital areas in preadolescents, and, after SO the younger group had higher slow delta activity in occipital areas. In preadolescents delta/beta ratio was higher in more posterior areas both before and after the wake-sleep transition and, after SO, preadolescents showed also a lower delta/beta ratio in frontal areas, compared to adults. Results point to a general higher homeostatic drive for the developing areas, consistently with plastic-related maturational modifications, that physiologically occur during preadolescence. • Preadolescents show the same electrophysiological spatiotemporal SO dynamics of adults, but with age-related peculiarities. • In preadolescents, the delta activity increases widely after SO with central maxima, and maximal values in the slowest bins. • Preadolescents have higher low beta PostSO, likely due to peculiar characterization of sleep spindles in term of frequency. • Compared to adults, preadolescents have more slow delta in occipital sites, both before and after SO. • Preadolescents have higher delta/beta ratio posteriorly Pre and PostSO; PostSO frontal ratio is lower, compared to adults. [ABSTRACT FROM AUTHOR]

BackgroundAlzheimer's disease (AD) pathology impairs cognitive function. Yet some individuals with high amounts of AD pathology suffer marked memory impairment, while others with the same degree of pathology burden show little impairment. Why is this? One proposed explanation is cognitive reserve i.e., factors that confer resilience against, or compensation for the effects of AD pathology. Deep NREM slow wave sleep (SWS) is recognized to enhance functions of learning and memory in healthy older adults. However, that the quality of NREM SWS (NREM slow wave activity, SWA) represents a novel cognitive reserve factor in older adults with AD pathology, thereby providing compensation against memory dysfunction otherwise caused by high AD pathology burden, remains unknown.MethodsHere, we tested this hypothesis in cognitively normal older adults (N = 62) by combining 11C-PiB (Pittsburgh compound B) positron emission tomography (PET) scanning for the quantification of β-amyloid (Aβ) with sleep electroencephalography (EEG) recordings to quantify NREM SWA and a hippocampal-dependent face-name learning task.ResultsWe demonstrated that NREM SWA significantly moderates the effect of Aβ status on memory function. Specifically, NREM SWA selectively supported superior memory function in individuals suffering high Aβ burden, i.e., those most in need of cognitive reserve (B = 2.694, p = 0.019). In contrast, those without significant Aβ pathological burden, and thus without the same  need for cognitive reserve, did not similarly benefit from the presence of NREM SWA (B = -0.115, p = 0.876). This interaction between NREM SWA and Aβ status predicting memory function was significant after correcting for age, sex, Body Mass Index, gray matter atrophy, and previously identified cognitive reserve factors, such as education and physical activity (p = 0.042).ConclusionsThese findings indicate that NREM SWA is a novel cognitive reserve factor providing resilience against the memory impairment otherwise caused by high AD pathology burden. Furthermore, this cognitive reserve function of NREM SWA remained significant when accounting both for covariates, and factors previously linked to resilience, suggesting that sleep might be an independent cognitive reserve resource. Beyond such mechanistic insights are potential therapeutic implications. Unlike many other cognitive reserve factors (e.g., years of education, prior job complexity), sleep is a modifiable factor. As such, it represents an intervention possibility that may aid the preservation of cognitive function in the face of AD pathology, both present moment and longitudinally.

Background: Disconnected consciousness describes a state in which subjective experience (i.e., consciousness) becomes isolated from the external world. It appears frequently during sleep or sedation, when subjective experiences remain vivid but are unaffected by external stimuli. Traditional methods of differentiating connected and disconnected consciousness, such as relying on behavioral responsiveness or on post-anesthesia reports, have demonstrated limited accuracy: unresponsiveness has been shown to not necessarily equate to unconsciousness and amnesic effects of anesthesia and sleep can impair explicit recollection of events occurred during sleep/sedation. Due to these methodological challenges, our understanding of the neural mechanisms underlying sensory disconnection remains limited. Methods: To overcome these methodological challenges, we employ a distinctive strategy by combining a serial awakening paradigm with auditory stimulation during mild propofol sedation. While under sedation, participants are systematically exposed to auditory stimuli and questioned about their subjective experience (to assess consciousness) and their awareness of the sounds (to evaluate connectedness/disconnectedness from the environment). The data collected through interviews are used to categorize participants into connected and disconnected consciousness states. This method circumvents the requirement for responsiveness in assessing consciousness and mitigates amnesic effects of anesthesia as participants are questioned while still under sedation. Functional MRI data are concurrently collected to investigate cerebral activity patterns during connected and disconnected states, to elucidate sensory disconnection neural gating mechanisms. We examine whether this gating mechanism resides at the thalamic level or results from disruptions in information propagation to higher cortices. Furthermore, we explore the potential role of slow-wave activity (SWA) in inducing disconnected consciousness by quantifying high-frequency BOLD oscillations, a known correlate of slow-wave activity. Discussion: This study represents a notable advancement in the investigation of sensory disconnection. The serial awakening paradigm effectively mitigates amnesic effects by collecting reports immediately after regaining responsiveness, while still under sedation. Ultimately, this research holds the potential to understand how sensory gating is achieved at the neural level. These biomarkers might be relevant for the development of sensitive anesthesia monitoring to avoid intraoperative connected consciousness and for the assessment of patients suffering from pathologically reduced consciousness. [ABSTRACT FROM AUTHOR]

Patients with Parkinson's disease (PD) tend to sleep more frequently in the supine position and less often change head and body position during sleep. Besides sleep quality and continuity, head and body positions are crucial for glymphatic system (GS) activity. This pilot study evaluated sleep architecture and head position during each sleep stage in idiopathic PD patients without cognitive impairment, correlating sleep data to patients' motor and non-motor symptoms (NMS). All patients underwent the multi-night recordings, which were acquired using the Sleep Profiler headband. Sleep parameters, sleep time in each head position, and percentage of slow wave activity (SWA) in sleep, stage 3 of non-REM sleep (N3), and REM sleep in the supine position were extracted. Lastly, correlations with motor impairment and NMS were performed. Twenty PD patients (65.7 ± 8.6 y.o, ten women) were included. Sleep architecture did not change across the different nights of recording and showed the prevalence of sleep performed in the supine position. In addition, SWA and N3 were more frequently in the supine head position, and N3 in the supine decubitus correlated with REM sleep performed in the same position; this latter correlated with the disease duration (correlation coefficient = 0.48, p-value = 0.03) and motor impairment (correlation coefficient = 0.53, p-value = 0.02). These preliminary results demonstrated the importance of monitoring sleep in PD patients, supporting the need for preventive strategies in clinical practice for maintaining the lateral head position during the crucial sleep stages (SWA, N3, REM), essential for permitting the GS function and activity and ensuring brain health. [ABSTRACT FROM AUTHOR]

BackgroundDisconnected consciousness describes a state in which subjective experience (i.e., consciousness) becomes isolated from the external world. It appears frequently during sleep or sedation, when subjective experiences remain vivid but are unaffected by external stimuli. Traditional methods of differentiating connected and disconnected consciousness, such as relying on behavioral responsiveness or on post-anesthesia reports, have demonstrated limited accuracy: unresponsiveness has been shown to not necessarily equate to unconsciousness and amnesic effects of anesthesia and sleep can impair explicit recollection of events occurred during sleep/sedation. Due to these methodological challenges, our understanding of the neural mechanisms underlying sensory disconnection remains limited.MethodsTo overcome these methodological challenges, we employ a distinctive strategy by combining a serial awakening paradigm with auditory stimulation during mild propofol sedation. While under sedation, participants are systematically exposed to auditory stimuli and questioned about their subjective experience (to assess consciousness) and their awareness of the sounds (to evaluate connectedness/disconnectedness from the environment). The data collected through interviews are used to categorize participants into connected and disconnected consciousness states. This method circumvents the requirement for responsiveness in assessing consciousness and mitigates amnesic effects of anesthesia as participants are questioned while still under sedation. Functional MRI data are concurrently collected to investigate cerebral activity patterns during connected and disconnected states, to elucidate sensory disconnection neural gating mechanisms. We examine whether this gating mechanism resides at the thalamic level or results from disruptions in information propagation to higher cortices. Furthermore, we explore the potential role of slow-wave activity (SWA) in inducing disconnected consciousness by quantifying high-frequency BOLD oscillations, a known correlate of slow-wave activity.DiscussionThis study represents a notable advancement in the investigation of sensory disconnection. The serial awakening paradigm effectively mitigates amnesic effects by collecting reports immediately after regaining responsiveness, while still under sedation. Ultimately, this research holds the potential to understand how sensory gating is achieved at the neural level. These biomarkers might be relevant for the development of sensitive anesthesia monitoring to avoid intraoperative connected consciousness and for the assessment of patients suffering from pathologically reduced consciousness.Clinical trial registrationEuropean Union Drug Regulating Authorities Clinical Trials Database (EudraCT), identifier 2020-003524-17.

Abstract Background Alzheimer’s disease (AD) pathology impairs cognitive function. Yet some individuals with high amounts of AD pathology suffer marked memory impairment, while others with the same degree of pathology burden show little impairment. Why is this? One proposed explanation is cognitive reserve i.e., factors that confer resilience against, or compensation for the effects of AD pathology. Deep NREM slow wave sleep (SWS) is recognized to enhance functions of learning and memory in healthy older adults. However, that the quality of NREM SWS (NREM slow wave activity, SWA) represents a novel cognitive reserve factor in older adults with AD pathology, thereby providing compensation against memory dysfunction otherwise caused by high AD pathology burden, remains unknown. Methods Here, we tested this hypothesis in cognitively normal older adults (N = 62) by combining 11C-PiB (Pittsburgh compound B) positron emission tomography (PET) scanning for the quantification of β-amyloid (Aβ) with sleep electroencephalography (EEG) recordings to quantify NREM SWA and a hippocampal-dependent face-name learning task. Results We demonstrated that NREM SWA significantly moderates the effect of Aβ status on memory function. Specifically, NREM SWA selectively supported superior memory function in individuals suffering high Aβ burden, i.e., those most in need of cognitive reserve (B = 2.694, p = 0.019). In contrast, those without significant Aβ pathological burden, and thus without the same need for cognitive reserve, did not similarly benefit from the presence of NREM SWA (B = -0.115, p = 0.876). This interaction between NREM SWA and Aβ status predicting memory function was significant after correcting for age, sex, Body Mass Index, gray matter atrophy, and previously identified cognitive reserve factors, such as education and physical activity (p = 0.042). Conclusions These findings indicate that NREM SWA is a novel cognitive reserve factor providing resilience against the memory impairment otherwise caused by high AD pathology burden. Furthermore, this cognitive reserve function of NREM SWA remained significant when accounting both for covariates, and factors previously linked to resilience, suggesting that sleep might be an independent cognitive reserve resource. Beyond such mechanistic insights are potential therapeutic implications. Unlike many other cognitive reserve factors (e.g., years of education, prior job complexity), sleep is a modifiable factor. As such, it represents an intervention possibility that may aid the preservation of cognitive function in the face of AD pathology, both present moment and longitudinally.

Objective: Individuals with epilepsy often have memory difficulties, and older adults with epilepsy are especially vulnerable, due to the additive effect of aging. The goal of this study was to assess factors that are associated with 24‐h memory retention in older adults with epilepsy. Methods: Fifty‐five adults with epilepsy, all aged >50 years, performed a declarative memory task involving the recall of the positions of 15 card pairs on a computer screen prior to a 24‐h ambulatory electroencephalogram (EEG). We assessed the percentage of encoded card pairs that were correctly recalled after 24 h (24‐h retention rate). EEGs were evaluated for the presence and frequency of scalp interictal epileptiform activity (IEA) and scored for total sleep. Global slow wave activity (SWA) power during non‐rapid eye movement sleep was also calculated. Results: Forty‐four participants successfully completed the memory task. Two were subsequently excluded due to seizures on EEG. The final cohort (n = 42) had a mean age of 64.3 ± 7.5 years, was 52% female, and had an average 24‐h retention rate of 70.9% ± 30.2%. Predictors of 24‐h retention based on multivariate regression analysis when controlling for age, sex, and education included number of antiseizure medications (β = −.20, p =.013), IEA frequency (β = −.08, p =.0094), and SWA power (β = +.002, p =.02). Significance: In older adults with epilepsy, greater frequency of IEA, reduced SWA power, and higher burden of antiseizure medications correlated with worse 24‐h memory retention. These factors represent potential treatment targets to improve memory in older adults with epilepsy. [ABSTRACT FROM AUTHOR]

Working memory is frequently impaired in children with complex congenital heart disease (CHD), but little is known about the functional neuronal correlates. Sleep slow wave activity (SWA; 1–4.5 Hz EEG power) has previously been shown to reliably map neurofunctional networks of cognitive abilities in children with and without neurodevelopmental impairments. This study investigated whether functional networks of working memory abilities are altered in children with complex CHD using EEG recordings during sleep. Twenty-one children with complex CHD (aged 10.9 [SD: 0.3] years) and 17 typically-developing peers (10.5 [0.7] years) completed different working memory tasks and an overnight high-density sleep EEG recording (128 electrodes). The combined working memory score tended to be lower in children with complex CHD (CHD group: −0.44 [1.12], typically-developing group: 0.55 [1.24], d = 0.59, p =.06). The working memory score and sleep SWA of the first hour of deep sleep were correlated over similar brain regions in both groups: Strong positive associations were found over prefrontal and fronto-parietal brain regions – known to be part of the working memory network – and strong negative associations were found over central brain regions. Within these working memory networks, the associations between working memory abilities and sleep SWA (r between −.36 and.58, all p <.03) were not different between the two groups (no interactions, all p >.05). The current findings suggest that sleep SWA reliably maps working memory networks in children with complex CHD and that these functional networks are generally preserved in these patients. [ABSTRACT FROM AUTHOR]

Sleep and memory are complex phenomena that are not fully understood, and the underlying mechanisms are still not fully understood. Besides being an adaptive behavior, sleep can modulate plasticity in the brain at the level of synaptic connections between neurons and neuronal plasticity affects sleep. Understanding how sleep is modulated by internal and external stimuli and how sleep modulates memory and plasticity is a key question in neuroscience. Sleep is characterized as a brain state that optimizes the memory consolidation. Although the initial encoding of a memory is a fast process, its long-term maintenance requires processes that continue to replace relevant data for hours or even years. The general name of this process is memory consolidation and the replacement of existing memories is the reconsolidation process. Memory consolidation refers to a process in which unstable newly formed memory traces are progressively transformed into long-term memories and become more resistant to interaction, although they may remain susceptible to further updates and modifications. Consolidation results from the reactivation of recently encoded neuronal memory representations that occur during slow-wave activity and transform the relevant representations into long-term memory for integration. Continued rapid eye movement sleep can stabilize transformed memories. According to recent research, sleep-related consolidation processes can be placed in different sizes for different types of memory. Slow wave activity, which is restorative sleep, is hypothesized to play an important role in memory by processing and consolidating newly acquired information. In this review, general research was conducted on the relationship between sleep and memory.

Sleep and memory are complex phenomena that are not fully understood, and the underlying mechanisms are still not fully understood. Besides being an adaptive behavior, sleep can modulate plasticity in the brain at the level of synaptic connections between neurons and neuronal plasticity affects sleep. Understanding how sleep is modulated by internal and external stimuli and how sleep modulates memory and plasticity is a key question in neuroscience. Sleep is characterized as a brain state that optimizes the memory consolidation. Although the initial encoding of a memory is a fast process, its long-term maintenance requires processes that continue to replace relevant data for hours or even years. The general name of this process is memory consolidation and the replacement of existing memories is the reconsolidation process. Memory consolidation refers to a process in which unstable newly formed memory traces are progressively transformed into long-term memories and become more resistant to interaction, although they may remain susceptible to further updates and modifications. Consolidation results from the reactivation of recently encoded neuronal memory representations that occur during slow-wave activity and transform the relevant representations into long-term memory for integration. Continued rapid eye movement sleep can stabilize transformed memories. According to recent research, sleep-related consolidation processes can be placed in different sizes for different types of memory. Slow wave activity, which is restorative sleep, is hypothesized to play an important role in memory by processing and consolidating newly acquired information. In this review, general research was conducted on the relationship between sleep and memory. [ABSTRACT FROM AUTHOR]

Study Objectives: Sleep slow wave activity, as measured using EEG delta power (

Objective/background: Slow wave activity (SWA) and sigma frequency activity (SFA) are hallmarks of NREM sleep EEG and important indicators of neural plasticity, development of the central nervous system, and cognition. However, little is known about the factors that modulate these sleep EEG activities, especially in small children.Patients/methods: We analyzed the power spectral densities of SWA (1-4 Hz) and SFA range (10-15 Hz) from six EEG derivations of 56 infants (8 months) and 60 toddlers (24 months) during their all-night sleep and during the first and the last half of night sleep. The spectral values were compared between the four seasons.Results: In the spring group of infants, compared with the darker seasons, SFA was lower in the centro-occipital EEG derivations during both halves of the night. The SWA findings of the infants were restricted to the last half of the night (SWA2) and frontally, where SWA2 was higher during winter than spring. The toddlers presented less frontal SWA2 during winter compared with autumn. Both age groups showed a reduction in both SWA and SFA towards the last half of the night.Conclusions: The sleep EEG spectral power densities are more often associated with seasons in infants' SFA range. The results might stem from seasonally changing light exposure, but the exact mechanism warrants further study. Moreover, contrary to the adult-like increment of SFA, the SFA at both ages was lower at the last part of the night sleep. This suggests different regulation of spindle activity in infants and toddlers. [ABSTRACT FROM AUTHOR]

Ultradian light–dark cycles in rodents are a precious tool to study the direct effects of repeated light exposures on sleep, in order to better understand the underlying mechanisms. This study aims to precisely evaluate the effects of light and dark exposures, according to circadian time, on sleep and waking distribution and quality, and to determine if these effects depend on the duration of light and dark pulses. To do this, mice were exposed to 24 h-long ultradian light–dark cycles with different durations of pulses: T2 cycle (1 h of light/1 h of dark) and T7 cycle (3.5 h of light/3.5 h of dark). Exposure to light not only promotes NREM and REM sleep and inhibits wake, but also drastically alters alertness and modifies sleep depth. These effects are modulated by circadian time, appearing especially during early subjective night, and their kinetics is highly dependent on the duration of pulses, suggesting that in the case of pulses of longer duration, the homeostatic process could overtake light direct influence for shaping sleep and waking distribution.

Objective: Levodopa-induced dyskinesia (DYS) adversely affects the quality of life of Parkinson's disease (PD) patients. However, few studies have focused on the relationship between DYS and sleep and electroencephalography (EEG). Our study aimed to establish the objective physiological indicators assessed by polysomnography (PSG) that are associated with DYS in PD patients., Methods: We enrolled 122 patients with PD, divided into two groups: PD with DYS (n = 27) and PD without DYS group (non-DYS, n = 95). The demographics and clinical characteristics and sleep assessment in the two groups were collected. More importantly, overnight six-channel PSG parameters were compared in the two groups. We also compared different bands and brain regions of average power spectral density within each group., Results: Compared with the non-DYS group, the DYS group tended to have a significantly higher percentage of nonrapid eye movement sleep (NREM). Gender, levodopa equivalent daily dose (LEDD), rapid eye movement (REM) sleep (min), and the NREM percentage were positively correlated with the occurrence of DYS. After adjusting for gender, disease duration, LEDD, taking amantadine or not, and Montreal Cognitive Assessment (MoCA), NREM%, N3%, and REM (min), the percentage of NREM sleep (p = 0.035), female (p = 0.002), and LEDD (p = 0.005), and REM sleep time (min) (p = 0.012) were still associated with DYS. There was no significant difference in whole-night different bands of average power spectral density between two groups. There was no significant difference in normalized average power spectral density of slow wave activity (SWA) (0.5-2 Hz, 0.5-4 Hz, and 2-4 Hz) of early and late NREM sleep in the DYS group. Dynamic normalized average power spectral density of SWA of low-frequency (0.5-2 Hz) reduction in the frontal region (p = 0.013) was associated with DYS in logistic regression after adjusting for confounding factors., Conclusion: PD patients with DYS have substantial sleep structure variations. Higher NREM percentage and less REM percentage were observed in PD patients with DYS. Dynamic normalized average power spectral density of low-frequency (0.5-2 Hz) SWA reduction in the frontal area could be a new electrophysiological marker of DYS in PD., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Previously, we presented our preliminary results (N = 14) investigating the effects of short-wavelength light from a smartphone during the evening on sleep and circadian rhythms (Höhn et al., 2021). Here, we now demonstrate our full sample (N = 33 men), where polysomnography and body temperature were recorded during three experimental nights and subjects read for 90 min on a smartphone with or without a filter or from a book. Cortisol, melatonin and affectivity were assessed before and after sleep. These results confirm our earlier findings, indicating reduced slow-wave-sleep and -activity in the first night quarter after reading on the smartphone without a filter. The same was true for the cortisol-awakening-response. Although subjective sleepiness was not affected, the evening melatonin increase was attenuated in both smartphone conditions. Accordingly, the distal-proximal skin temperature gradient increased less after short-wavelength light exposure than after reading a book. Interestingly, we could unravel within this full dataset that higher positive affectivity in the evening predicted better subjective but not objective sleep quality. Our results show disruptive consequences of short-wavelength light for sleep and circadian rhythmicity with a partially attenuating effect of blue-light filters. Furthermore, affective states influence subjective sleep quality and should be considered, whenever investigating sleep and circadian rhythms.

Acute cocaine disturbs sleep on a dose-dependent basis; however, the consequences of chronic cocaine remain unclear. While the arousal promotion following cocaine has been well-established, effects of cocaine on sleep after termination of chronic cocaine exposure appear variable in human subjects with few studies in non-human subjects. Here, a within-subjects design (outcomes normalized to baseline, undisturbed behavior) and between-subjects design (repeated experimenter-administered cocaine vs. experimenter-administered saline) was used to investigate sleep homeostasis and sleep/waking under repeated cocaine/saline exposure and prolonged forced abstinence conditions in mice. Overall, during the forced abstinence period increases in arousal, as determined by sleep latency and gamma energy, persisted for 2 weeks. However, the sleep response to externally enforced sleep deprivation was unchanged suggesting that sleep disruptions during the forced abstinence period were driven by enhancement of arousal in the absence of changes in sleep homeostatic responses. [ABSTRACT FROM AUTHOR]

PCDH19 epilepsy (DEE9) is an X-linked syndrome associated with cognitive and behavioral disturbances. Since heterozygous females are affected, while mutant males are spared, it is likely that DEE9 pathogenesis is related to disturbed cell-to-cell communication associated with mosaicism. However, the effects of mosaic PCDH19 expression on cortical networks are unknown. We mimicked the pathology of DEE9 by introducing a patch of mosaic protein expression in one hemisphere of the cortex of conditional PCDH19 knockout mice one day after birth. In the contralateral area, PCDH19 expression was unaffected, thus providing an internal control. In this model, we characterized the physiology of the disrupted network using local field recordings and two photon Ca2+ imaging in urethane anesthetized mice. We found transient episodes of hyperexcitability in the form of brief hypersynchronous spikes or bursts of field potential oscillations in the 9–25 Hz range. Furthermore, we observed a strong disruption of slow wave activity, a crucial component of NREM sleep. This phenotype was present also when PCDH19 loss occurred in adult mice, demonstrating that PCDH19 exerts a function on cortical circuitry outside of early development. Our results indicate that a focal mosaic mutation of PCDH19 disrupts cortical networks and broaden our understanding of DEE9. [ABSTRACT FROM AUTHOR]

Ultradian light–dark cycles in rodents are a precious tool to study the direct effects of repeated light exposures on sleep, in order to better understand the underlying mechanisms. This study aims to precisely evaluate the effects of light and dark exposures, according to circadian time, on sleep and waking distribution and quality, and to determine if these effects depend on the duration of light and dark pulses. To do this, mice were exposed to 24 h-long ultradian light–dark cycles with different durations of pulses: T2 cycle (1 h of light/1 h of dark) and T7 cycle (3.5 h of light/3.5 h of dark). Exposure to light not only promotes NREM and REM sleep and inhibits wake, but also drastically alters alertness and modifies sleep depth. These effects are modulated by circadian time, appearing especially during early subjective night, and their kinetics is highly dependent on the duration of pulses, suggesting that in the case of pulses of longer duration, the homeostatic process could overtake light direct influence for shaping sleep and waking distribution. [ABSTRACT FROM AUTHOR]

Acute cocaine disturbs sleep on a dose-dependent basis; however, the consequences of chronic cocaine remain unclear. While the arousal promotion following cocaine has been well-established, effects of cocaine on sleep after termination of chronic cocaine exposure appear variable in human subjects with few studies in non-human subjects. Here, a within-subjects design (outcomes normalized to baseline, undisturbed behavior) and between-subjects design (repeated experimenter-administered cocaine vs. experimenter-administered saline) was used to investigate sleep homeostasis and sleep/waking under repeated cocaine/saline exposure and prolonged forced abstinence conditions in mice. Overall, during the forced abstinence period increases in arousal, as determined by sleep latency and gamma energy, persisted for 2 weeks. However, the sleep response to externally enforced sleep deprivation was unchanged suggesting that sleep disruptions during the forced abstinence period were driven by enhancement of arousal in the absence of changes in sleep homeostatic responses.

Background: Sleep slow wave activity (SWA) peaks during childhood and declines in the transition to adolescence during typical development (TD). It remains unknown whether this trajectory differs in youth with neuropsychiatric disorders.Methods: We analyzed sleep EEGs of 664 subjects 6 to 21 y (449 TD, 123 unmedicated, 92 medicated) and 114 subjects 7-12 y (median 10.5 y) followed-up at 18-22 y (median 19 y). SWA (0.4-4 Hz) power was calculated during non-rapid eye movement sleep.Results: TD and unmedicated youth showed cubic central and frontal SWA trajectories from 6 to 21 y (p-cubic<0.05), with TD youth showing peaks in central SWA at 6.8 y and frontal at 8.2 y. Unmedicated attention-deficit/hyperactivity (ADHD) and/or learning disorders (LD) showed peak central SWA 2 y later (at 9.6 y, coinciding with peak frontal SWA) than TD, followed by a 67% steeper slope by 19 y. Frontal SWA peak and slope in unmedicated ADHD/LD, and that of central and frontal in internalizing disorders (ID), were similar to TD. Unmedicated ADHD/LD did not differ in the longitudinal SWA percent change by 18-22 y; unmedicated ID showed a lower longitudinal change in frontal SWA than TD. Medicated youth showed a linear decline in central and frontal SWA from 6 to 21 y (p-linear<0.05).Conclusions: ADHD/LD youth show a maturational delay and potential topographical disruption in SWA during childhood and steeper decline throughout adolescence, suggesting faster synaptic pruning. Youth with ID experience less changes in frontal SWA by late adolescence. Psychotropic medications may impact the maturational trajectory of SWA, but not the magnitude of developmental decline by late adolescence. [ABSTRACT FROM AUTHOR]

Sleep deprivation impairs the formation of new memories. However, marked interindividual variability exists in the degree to which sleep loss compromises learning, the mechanistic reasons for which are unclear. Furthermore, which physiological sleep processes restore learning ability following sleep deprivation are similarly unknown. Here, we demonstrate that the structural morphology of human hippocampal subfields represents one factor determining vulnerability (and conversely, resilience) to the impact of sleep deprivation on memory formation. Moreover, this same measure of brain morphology was further associated with the quality of nonrapid eye movement slow wave oscillations during recovery sleep, and by way of such activity, determined the success of memory restoration. Such findings provide a novel human biomarker of cognitive susceptibility to, and recovery from, sleep deprivation. Moreover, this metric may be of special predictive utility for professions in which memory function is paramount yet insufficient sleep is pervasive (e.g., aviation, military, and medicine).

Previously, we presented our preliminary results (N = 14) investigating the effects of short-wavelength light from a smartphone during the evening on sleep and circadian rhythms (Höhn et al., 2021). Here, we now demonstrate our full sample (N = 33 men), where polysomnography and body temperature were recorded during three experimental nights and subjects read for 90 min on a smartphone with or without a filter or from a book. Cortisol, melatonin and affectivity were assessed before and after sleep. These results confirm our earlier findings, indicating reduced slow-wave-sleep and -activity in the first night quarter after reading on the smartphone without a filter. The same was true for the cortisol-awakening-response. Although subjective sleepiness was not affected, the evening melatonin increase was attenuated in both smartphone conditions. Accordingly, the distal-proximal skin temperature gradient increased less after short-wavelength light exposure than after reading a book. Interestingly, we could unravel within this full dataset that higher positive affectivity in the evening predicted better subjective but not objective sleep quality. Our results show disruptive consequences of short-wavelength light for sleep and circadian rhythmicity with a partially attenuating effect of blue-light filters. Furthermore, affective states influence subjective sleep quality and should be considered, whenever investigating sleep and circadian rhythms. [ABSTRACT FROM AUTHOR]

Aurora D’Atri,1,2 Serena Scarpelli,1 Maurizio Gorgoni,1 Valentina Alfonsi,1 Ludovica Annarumma,1 Anna Maria Giannini,1 Michele Ferrara,3 Fabio Ferlazzo,1 Paolo Maria Rossini,4,5 Luigi De Gennaro1,2 1Department of Psychology, University of Rome “Sapienza”, Rome, Italy; 2Area of Neuroscience, IRCCS San Raffaele Pisana, Rome, Italy; 3Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy; 4Institute of Neurology, Catholic University of the Sacred Heart, Rome, Italy; 5Department Geriatrics, Neuroscience & Orthopaedics, Policlinic A. Gemelli Foundation-IRCCS, Rome, ItalyCorrespondence: Luigi De GennaroDepartment of Psychology, University of Rome “Sapienza”, Via Dei Marsi, 78, Rome 00185, Italy, Tel +39 06-49917647Fax +39 06-49917711Email luigi.degennaro@uniroma1.itPurpose: Recent studies demonstrate that 5-Hz bilateral transcranial alternating current stimulation (θ-tACS) on fronto-temporal areas affects resting EEG enhancing cortical synchronization, but it does not affect subjective sleepiness. This dissociation raises questions on the resemblance of this effect to the physiological falling asleep process. The current study aimed to evaluate the ability of fronto-temporal θ-tACS to promote sleep.Subjects and methods: Twenty subjects (10 F/10 M; mean age: 24.60 ± 2.9 y) participated in a single-blind study consisting of two within-subject sessions (active/sham), one week apart in counterbalanced order. Stimulation effects on EEG were assessed during wake and post-stimulation nap. The final sample included participants who fell asleep in both sessions (n=17).Results: Group analyses on the whole sample reported no θ-tACS effects on subjective sleepiness and sleep measures, while a different scenario came to light by analysing data of responders to the stimulation (ie, subjects actually showing the expected increase of theta activity in the wake EEG after the θ-tACS, n=7). Responders reported a significant increase in subjective sleepiness during wakefulness after the active stimulation as compared to the sham. Moreover, the sleep after the θ-tACS compared to sham in this sub-group showed: (1) greater slow-wave activity (SWA); (2) SWA time-course revealing increases much larger as closer to the sleep onset; (3) stimulation-induced changes in SWA during sleep topographically associated to those in theta activity during wake.Conclusion: Subjects who show the expected changes during wake after the stimulation also had a consistent pattern of changes during sleep. The enhancement of cortical synchronization by θ-tACS during wakefulness actually corresponds to increased sleep pressure, but it occurs only in some individuals. Thus, θ-tACS can enhance sleep, although individual factors to be further investigated affect the actual responsiveness to this treatment.Keywords: transcranial alternating current stimulation, sleep, EEG, slow-wave activity, sleep onset

Background: Brain maturation is reflected in the sleep electroencephalogram (EEG) by a decline in non-rapid eye movement (NREM) slow wave activity (SWA) throughout adolescence and a related decrease in sleep depth. However, this trajectory and its sex and pubertal differences lack replication in population-based samples. We tested age-related changes in SWA (0.4-4 Hz) power and odds ratio product (ORP), a standardized measure of sleep depth.Methods: We analyzed the sleep EEG of 572 subjects aged 6-21 y (48% female, 26% racial/ethnic minority) and 332 subjects 5-12 y followed-up at 12-22 y. Multivariable-adjusted analyses tested age-related cross-sectional and longitudinal trajectories of SWA and ORP.Results: SWA remained stable from age 6 to 10, decreased between ages 11 and 17, and plateaued from age 18 to 21 (p-cubic<0.001); females showed a longitudinal decline 23% greater than males by 13 y, while males experienced a steeper slope after 14 y and their longitudinal decline was 21% greater by 19 y. More mature adolescents (75% female) experienced a greater longitudinal decline in SWA than less mature adolescents by 14 y. ORP showed an age-related increasing trajectory (p-linear<0.001) with no sex or pubertal differences.Conclusions: We provide population-level evidence for the maturational decline and sex and pubertal differences in SWA in the transition from childhood to adolescence, while introducing ORP as a novel metric in youth. Along with previous studies, the distinct trajectories observed suggest that age-related changes in SWA reflect brain maturation and local/synaptic processes during this developmental period, while those of ORP may reflect global/state control of NREM sleep depth. [ABSTRACT FROM AUTHOR]

Study Objectives: A decline in sleep quality, slow wave sleep (SWS) and slow wave activity (SWA) are common in older adults. Prior studies have shown that manipulating body temperature during sleep can increase SWS/SWA. The aim of this study was to determine the effects of manipulation of body temperatures during sleep, using a high heat capacity mattress, on SWS/SWA and heart rate in post-menopausal women.Methods: Twenty-four healthy postmenopausal women between 40 and 75 years of age (mean age 62.4 ± 8.2 years, mean BMI 25.4 ± 3.5 kg/m2) were randomized in a single-blind, counterbalanced, cross-over manner to sleep on either a high heat capacity mattress (HHCM) or a low heat capacity mattress (LHCM) a week apart. Sleep was recorded using polysomnography during an 8-h sleep opportunity. Core and peripheral temperature were recorded using an ingestible capsule and thermochron respectively.Results: In comparison to the LHCM, sleep on HHCM exhibited a selective increase in SWS (average increase in Stage N3 of 9.6 min (2.1%), p = 0.04) and in slow oscillatory (SO) activity (0.5-1 Hz) in the first NREM/REM cycle (p = 0.04). In addition, the HHCM induced a greater reduction in core body temperature (p = 0.002). The reduction in core body temperature (first 180 min after lights out) from LHCM to HHCM was associated (r = 0.5, p = 0.012) with the increase in SO activity (SO cycle 1 and 2/cycle 3 and 4). Average heart rate was 1.6 beats/minute lower across the night on the HHCM compared to the LHCM (p = 0.001).Conclusions: The results of this study indicate that manipulation of body temperature during sleep may be a useful approach to enhance SWS sleep in postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: Novel preventive therapies are needed for postoperative delirium, which especially affects older patients. A mouse model is presented that captures inflammation-associated cortical slow wave activity (SWA) observed in patients, allowing exploration of the mechanistic role of prostaglandin-adenosine signalling.Methods: EEG and cortical cytokine measurements (interleukin 6, monocyte chemoattractant protein-1) were obtained from adult and aged mice. Behaviour, SWA, and functional connectivity were assayed before and after systemic administration of lipopolysaccharide (LPS)+piroxicam (cyclooxygenase inhibitor) or LPS+caffeine (adenosine receptor antagonist). To avoid the confounder of inflammation-driven changes in movement which alter SWA and connectivity, electrophysiological recordings were classified as occurring during quiescence or movement, and propensity score matching was used to match distributions of movement magnitude between baseline and post-LPS administration.Results: LPS produces increases in cortical cytokines and behavioural quiescence. In movement-matched data, LPS produces increases in SWA (likelihood-ratio test: χ2(4)=21.51, P<0.001), but not connectivity (χ2(4)=6.39, P=0.17). Increases in SWA associate with interleukin 6 (P<0.001) and monocyte chemoattractant protein-1 (P=0.001) and are suppressed by piroxicam (P<0.001) and caffeine (P=0.046). Aged animals compared with adult animals show similar LPS-induced SWA during movement, but exaggerated cytokine response and increased SWA during quiescence.Conclusions: Cytokine-SWA correlations during wakefulness are consistent with observations in patients with delirium. Absence of connectivity effects after accounting for movement changes suggests decreased connectivity in patients is a biomarker of hypoactivity. Exaggerated effects in quiescent aged animals are consistent with increased hypoactive delirium in older patients. Prostaglandin-adenosine signalling may link inflammation to neural changes and hence delirium. [ABSTRACT FROM AUTHOR]

Sleep disorders are one of the significant problems in the modern society. Current research is on the lookout for the nonpharmacological ways to improve sleep quality and slow wave brain activity that plays a crucial role in homeostasis and cognitive functions. One of the promising approaches is acoustic stimulation that is phase-locked to deep sleep EEG rhythms. It was already shown that such stimulation improves slow wave brain activity. This article describes Dreem: a wireless consumer device that performs acoustic sleep stimulation in home conditions. The device has dry EEG electrodes, photo sensor for pulse oximetry, and an accelerometer. The inbuilt software detects deep sleep, performs audio stimulation on the ascending slope of the delta wave and does automatic sleep staging. In the pilot study of the device, three subjects made 10 to 24 recordings of night sleep with EEG recording and stimulation. The raw data recorded by the device is available to the user and is sufficient for sleep staging and basic sleep analysis. Automatic hypnograms reflect the structure of a normal night sleep. EEG averaged by the stimulation markers demonstrated the high efficacy of slow wave detectors and placement of stimulations on the ascending slope of a delta wave. Dreem device is of interest for the sleep researchers as an easy to use tool for an out-of-lab data acquisition.

PCDH19 epilepsy (DEE9) is an X-linked syndrome associated with cognitive and behavioral disturbances. Since heterozygous females are affected, while mutant males are spared, it is likely that DEE9 pathogenesis is related to disturbed cell-to-cell communication associated with mosaicism. However, the effects of mosaic PCDH19 expression on cortical networks are unknown. We mimicked the pathology of DEE9 by introducing a patch of mosaic protein expression in one hemisphere of the cortex of conditional PCDH19 knockout mice one day after birth. In the contralateral area, PCDH19 expression was unaffected, thus providing an internal control. In this model, we characterized the physiology of the disrupted network using local field recordings and two photon Ca2+ imaging in urethane anesthetized mice. We found transient episodes of hyperexcitability in the form of brief hypersynchronous spikes or bursts of field potential oscillations in the 9–25 Hz range. Furthermore, we observed a strong disruption of slow wave activity, a crucial component of NREM sleep. This phenotype was present also when PCDH19 loss occurred in adult mice, demonstrating that PCDH19 exerts a function on cortical circuitry outside of early development. Our results indicate that a focal mosaic mutation of PCDH19 disrupts cortical networks and broaden our understanding of DEE9.

Smartphone usage strongly increased in the last decade, especially before bedtime. There is growing evidence that short-wavelength light affects hormonal secretion, thermoregulation, sleep and alertness. Whether blue light filters can attenuate these negative effects is still not clear. Therefore, here, we present preliminary data of 14 male participants (21.93 ± 2.17 years), who spent three nights in the sleep laboratory, reading 90 min either on a smartphone (1) with or (2) without a blue light filter, or (3) on printed material before bedtime. Subjective sleepiness was decreased during reading on a smartphone, but no effects were present on evening objective alertness in a GO/NOGO task. Cortisol was elevated in the morning after reading on the smartphone without a filter, which resulted in a reduced cortisol awakening response. Evening melatonin and nightly vasodilation (i.e., distalproximal skin temperature gradient) were increased after reading on printed material. Early slow wave sleep/activity and objective alertness in the morning were only reduced after reading without a filter. These results indicate that short-wavelength light affects not only circadian rhythm and evening sleepiness but causes further effects on sleep physiology and alertness in the morning. Using a blue light filter in the evening partially reduces these negative effects. [ABSTRACT FROM AUTHOR]

Objective: In recognition of the mixed associations between traditionally scored slow wave sleep and memory, we sought to explore the relationships between slow wave sleep, electroencephalographic (EEG) power spectra during sleep and overnight verbal memory retention in older adults.Design, Setting, Participants, and Measurements: Participants were 101 adults without dementia (52% female, mean age 70.3 years). Delayed verbal memory was first tested in the evening prior to overnight polysomnography (PSG). The following morning, subjects were asked to recall as many items as possible from the same List (overnight memory retention; OMR). Partial correlation analyses examined the associations of delayed verbal memory and OMR with slow wave sleep (SWS) and two physiologic EEG slow wave activity (SWA) power spectral bands (0.5–1 Hz slow oscillations vs. 1–4 Hz delta activity).Results: In subjects displaying SWS, SWS was associated with enhanced delayed verbal memory, but not with OMR. Interestingly, among participants that did not show SWS, OMR was significantly associated with a higher slow oscillation relative power, during NREM sleep in the first ultradian cycle, with medium effect size.Conclusions: These findings suggest a complex relationship between SWS and memory and illustrate that even in the absence of scorable SWS, older adults demonstrate substantial slow wave activity. Further, these slow oscillations (0.5–1 Hz), in the first ultradian cycle, are positively associated with OMR, but only in those without SWS. Our findings raise the possibility that precise features of slow wave activity play key roles in maintaining memory function in healthy aging. Further, our results underscore that conventional methods of sleep evaluation may not be sufficiently sensitive to detect associations between SWA and memory in older adults.

Objective: In recognition of the mixed associations between traditionally scored slow wave sleep and memory, we sought to explore the relationships between slow wave sleep, electroencephalographic (EEG) power spectra during sleep and overnight verbal memory retention in older adults. Design, Setting, Participants, and Measurements: Participants were 101 adults without dementia (52% female, mean age 70.3 years). Delayed verbal memory was first tested in the evening prior to overnight polysomnography (PSG). The following morning, subjects were asked to recall as many items as possible from the same List (overnight memory retention; OMR). Partial correlation analyses examined the associations of delayed verbal memory and OMR with slow wave sleep (SWS) and two physiologic EEG slow wave activity (SWA) power spectral bands (0.5–1 Hz slow oscillations vs. 1–4 Hz delta activity). Results: In subjects displaying SWS, SWS was associated with enhanced delayed verbal memory, but not with OMR. Interestingly, among participants that did not show SWS, OMR was significantly associated with a higher slow oscillation relative power, during NREM sleep in the first ultradian cycle, with medium effect size. Conclusions: These findings suggest a complex relationship between SWS and memory and illustrate that even in the absence of scorable SWS, older adults demonstrate substantial slow wave activity. Further, these slow oscillations (0.5–1 Hz), in the first ultradian cycle, are positively associated with OMR, but only in those without SWS. Our findings raise the possibility that precise features of slow wave activity play key roles in maintaining memory function in healthy aging. Further, our results underscore that conventional methods of sleep evaluation may not be sufficiently sensitive to detect associations between SWA and memory in older adults. [ABSTRACT FROM AUTHOR]

Neuronal activity and gene expression in response to the loss of sleep can provide a window into the enigma of sleep function. Sleep loss is associated with brain differential gene expression, an increase in pyramidal cell mEPSC frequency and amplitude, and a characteristic rebound and resolution of slow wave sleep-slow wave activity (SWS-SWA). However, the molecular mechanism(s) mediating the sleep-loss response are not well understood. We show that sleep-loss regulates MEF2C phosphorylation, a key mechanism regulating MEF2C transcriptional activity, and that MEF2C function in postnatal excitatory forebrain neurons is required for the biological events in response to sleep loss in C57BL/6J mice. These include altered gene expression, the increase and recovery of synaptic strength, and the rebound and resolution of SWS-SWA, which implicate MEF2C as an essential regulator of sleep function.

Alzheimer’s disease (AD) is the major cause of dementia, characterized by the presence of amyloid-beta plaques and neurofibrillary tau tangles. Plaques and tangles are associated with sleep-wake cycle disruptions, including the disruptions in non-rapid eye movement (NREM) slow wave sleep (SWS). Alzheimer’s patients spend less time in NREM sleep and exhibit decreased slow wave activity (SWA). Consistent with the critical role of SWS in memory consolidation, reduced SWA is associated with impaired memory consolidation in AD patients. The aberrant SWA can be modeled in transgenic mouse models of amyloidosis and tauopathy. Animal models exhibited slow wave impairments early in the disease progression, prior to the deposition of amyloid-beta plaques, however, in the presence of abundant oligomeric amyloid-beta. Optogenetic rescue of SWA successfully halted the amyloid accumulation and restored intraneuronal calcium levels in mice. On the other hand, optogenetic acceleration of slow wave frequency exacerbated amyloid deposition and disrupted neuronal calcium homeostasis. In this review, we summarize the evidence and the mechanisms underlying the existence of a positive feedback loop between amyloid/tau pathology and SWA disruptions that lead to further accumulations of amyloid and tau in AD. Moreover, since SWA disruptions occur prior to the plaque deposition, SWA disruptions may provide an early biomarker for AD. Finally, we propose that therapeutic targeting of SWA in AD might lead to an effective treatment for Alzheimer’s patients.

Abstract Circadian rhythms and sleep-wake history determine sleep duration and intensity, and influence subsequent waking. Previous studies have shown that T cycles - light-dark (LD) cycles differing from 24 h - lead to acute changes in the daily amount and distribution of waking and sleep. However, little is known about the long-term effects of T cycles. Here we performed continuous 10 day recording of electroencephalography (EEG), locomotor activity and core body temperature in C57BL/6 mice under a T20 cycle, to investigate spontaneous sleep and waking at baseline compared with when the circadian clock was misaligned and then re-aligned with respect to the external LD cycle. We found that the rhythmic distribution of sleep was abolished during misalignment, while the time course of EEG slow wave activity (1–4 Hz) was inverted compared to baseline. Although the typical light-dark distribution of NREM sleep was re-instated when animals were re-aligned, slow wave activity during NREM sleep showed an atypical increase in the dark phase, suggesting a long-term effect of T cycles on sleep intensity. Our data show that circadian misalignment results in previously uncharacterised long-term effects on sleep, which may have important consequences for behaviour.

The role of dopamine in regulating sleep‐state transitions during, both natural sleep and under anaesthesia, is still unclear. Recording in vivo in the rat mPFC under urethane anaesthesia, we observed predominantly slow wave activity (SWA) of <1 Hz in the local field potential interrupted by occasional spontaneous transitions to a low‐amplitude‐fast (LAF) pattern of activity. During periods of SWA, transitions to LAF activity could be rapidly and consistently evoked by electrical stimulation of the ventral tegmental area (VTA). Spontaneous LAF activity, and that evoked by stimulation of the VTA, consisted of fast oscillations similar to those seen in the rapid eye movement (REM)‐like sleep state. Spontaneous and VTA stimulation‐evoked LAF activity occurred simultaneously along the dorsoventral extent of all mPFC subregions. Evoked LAF activity depended on VTA stimulation current and could be elicited using either regular (25–50 Hz) or burst stimulation patterns and was reproducible upon repeated stimulation. Simultaneous extracellular single‐unit recordings showed that during SWA, presumed pyramidal cells fired phasically and almost exclusively on the Up state, while during both spontaneous and VTA‐evoked LAF activity, they fired tonically. The transition to LAF activity evoked by VTA stimulation depended on dopamine D1‐like receptor activation as it was almost completely blocked by systemic administration of the D1‐like receptor antagonist SCH23390. Overall, our data demonstrate that activation of dopamine D1‐like receptors in the mPFC is important for regulating sleep‐like state transitions. [ABSTRACT FROM AUTHOR]

Background: Delirium frequently affects older patients, increasing morbidity and mortality; however, the pathogenesis is poorly understood. Herein, we tested the cognitive disintegration model, which proposes that a breakdown in frontoparietal connectivity, provoked by increased slow-wave activity (SWA), causes delirium.Methods: We recruited 70 surgical patients to have preoperative and postoperative cognitive testing, EEG, blood biomarkers, and preoperative MRI. To provide evidence for causality, any putative mechanism had to differentiate on the diagnosis of delirium; change proportionally to delirium severity; and correlate with a known precipitant for delirium, inflammation. Analyses were adjusted for multiple corrections (MCs) where appropriate.Results: In the preoperative period, subjects who subsequently incurred postoperative delirium had higher alpha power, increased alpha band connectivity (MC P<0.05), but impaired structural connectivity (increased radial diffusivity; MC P<0.05) on diffusion tensor imaging. These connectivity effects were correlated (r2=0.491; P=0.0012). Postoperatively, local SWA over frontal cortex was insufficient to cause delirium. Rather, delirium was associated with increased SWA involving occipitoparietal and frontal cortex, with an accompanying breakdown in functional connectivity. Changes in connectivity correlated with SWA (r2=0.257; P<0.0001), delirium severity rating (r2=0.195; P<0.001), interleukin 10 (r2=0.152; P=0.008), and monocyte chemoattractant protein 1 (r2=0.253; P<0.001).Conclusions: Whilst frontal SWA occurs in all postoperative patients, delirium results when SWA progresses to involve posterior brain regions, with an associated reduction in connectivity in most subjects. Modifying SWA and connectivity may offer a novel therapeutic approach for delirium.Clinical Trial Registration: NCT03124303, NCT02926417. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the major cause of dementia, characterized by the presence of amyloid-beta plaques and neurofibrillary tau tangles. Plaques and tangles are associated with sleep-wake cycle disruptions, including the disruptions in non-rapid eye movement (NREM) slow wave sleep (SWS). Alzheimer's patients spend less time in NREM sleep and exhibit decreased slow wave activity (SWA). Consistent with the critical role of SWS in memory consolidation, reduced SWA is associated with impaired memory consolidation in AD patients. The aberrant SWA can be modeled in transgenic mouse models of amyloidosis and tauopathy. Animal models exhibited slow wave impairments early in the disease progression, prior to the deposition of amyloid-beta plaques, however, in the presence of abundant oligomeric amyloid-beta. Optogenetic rescue of SWA successfully halted the amyloid accumulation and restored intraneuronal calcium levels in mice. On the other hand, optogenetic acceleration of slow wave frequency exacerbated amyloid deposition and disrupted neuronal calcium homeostasis. In this review, we summarize the evidence and the mechanisms underlying the existence of a positive feedback loop between amyloid/tau pathology and SWA disruptions that lead to further accumulations of amyloid and tau in AD. Moreover, since SWA disruptions occur prior to the plaque deposition, SWA disruptions may provide an early biomarker for AD. Finally, we propose that therapeutic targeting of SWA in AD might lead to an effective treatment for Alzheimer's patients. [ABSTRACT FROM AUTHOR]

• Effect of lifelong omega-3 deficiency on sleep in physiology and under inflammation. • Omega-3 deficiency affects the architecture of sleep-wake activity. • Omega-3 deficiency decreases the amplitude of delta oscillations during NREM sleep. • Omega-3 deficiency affects the REM sleep response to an acute inflammatory challenge. Essential polyunsaturated fatty acids (PUFA) from the n-3 and n-6 series constitute the building blocks of brain cell membranes where they regulate most aspects of cell physiology. They are either biosynthesized from their dietary precursors or can be directly sourced from the diet. An overall increase in the dietary n-6/n-3 PUFA ratio, as observed in the Western diet, leads to reduced n-3 PUFAs in tissues that include the brain. Some clinical studies have shown a positive correlation between dietary n-3 PUFA intake and sleep quantity, yet evidence is still sparse. We here used a preclinical model of dietary n-3 PUFA deficiency to assess the precise relationship between dietary PUFA intake and sleep/wake activity. Using electroencephalography (EEG)/electromyography (EMG) recordings on n-3 PUFA deficient or sufficient mice, we showed that dietary PUFA deficiency affects the architecture of sleep-wake activity and the oscillatory activity of cortical neurons during sleep. In a second part of the study, and since PUFAs are a potent modulator of inflammation, we assessed the effect of dietary n-3 PUFA deficiency on the sleep response to an inflammatory stimulus known to modulate sleep/wake activity. We injected mice with the endotoxin lipopolysaccharide (LPS) and quantified the sleep response across the following 12 h. Our results revealed that n-3 PUFA deficiency affects the sleep response in basal condition and after a peripheral immune challenge. More studies are now required aimed at deciphering the molecular mechanisms underlying the intimate relationship between n-3 PUFAs and sleep/wake activity. [ABSTRACT FROM AUTHOR]

Background: Previous work on the electroencephalographic (EEG) effects of anaesthetic doses of ketamine has identified a characteristic signature of increased high frequency (beta-gamma) and theta waves alternating with episodic slow waves. It is unclear which EEG parameter is optimal for pharmacokinetic-pharmacodynamic modelling of the hypnotic actions of ketamine, or which EEG parameter is most closely linked to loss of behavioural responsiveness.Methods: We re-analysed previously published 128-channel scalp EEG data from 15 subjects who had received a 1.5 mg kg-1 bolus i.v. dose of ketamine. We applied standard sigmoid pharmacokinetic-pharmacodynamic models to the drug-induced changes in slow wave activity, theta, and beta-gamma EEG power; and examined the morphology of the slow waves in the time domain for Fz, F3, T3, P3, and Pz average-referenced channels.Results: Hypnotic doses of ketamine i.v. induced medio-frontal EEG slow waves, and loss of behavioural response when the estimated brain concentration was 1.64 (0.17) μg ml-1. Recovery of responsiveness occurred at 1.06 (0.21) μg.ml-1 after slow wave activity had markedly diminished. Pharmacokinetic-pharmacodynamic modelling fitted best to the slow wave activity and theta power (almost half the beta-gamma channels could not be modelled). Slow wave effect-site equilibration half-time (23 [4] s), and offset, was faster than for theta (47 [22] s).Conclusions: Changes in EEG slow wave activity after a hypnotic dose of ketamine could be fitted by a standard sigmoid dose-response model. Their onset, but not their offset, was consistently associated with loss of behavioural response in our small study group. [ABSTRACT FROM AUTHOR]

Healthy aging is characterized by macrostructural sleep changes and alterations of regional electroencephalographic (EEG) sleep features. However, the spatiotemporal EEG pattern of the wake-sleep transition has never been described in the elderly. The present study aimed to assess the topographical and temporal features of the EEG during the sleep onset (SO) in a group of 36 older participants (59–81 years). The topography of the 1 Hz bins’ EEG power and the time course of the EEG frequency bands were assessed. Moreover, we compared the delta activity and delta/beta ratio between the older participants and a group of young adults. The results point to several peculiarities in the elderly: (a) the generalized post-SO power increase in the slowest frequencies did not include the 7 Hz bin; (b) the alpha power revealed a frequency-specific pattern of post-SO modifications; (c) the sigma activity exhibited only a slight post-SO increase, and its highest bins showed a frontotemporal power decrease. Older adults showed a generalized reduction of delta power and delta/beta ratio in both pre- and post-SO intervals compared to young adults. From a clinical standpoint, the regional EEG activity may represent a target for brain stimulation techniques to reduce SO latency and sleep fragmentation.