Topographical aspects in the dynamics of sleep homeostasis in young men: individual patterns

BACKGROUND: Sleep homeostasis refers to the increase of sleep pressure during waking and the decrease of sleep intensity during sleep. Electroencephalography (EEG) slow-wave activity (SWA; EEG power in the 0.75-4.5 Hz range) is a marker of non-rapid eye movement (NREM) sleep intensity and can be used to model sleep homeostasis (Process S). SWA shows a frontal predominance, and its increase after sleep deprivation is most pronounced in frontal areas. The question arises whether the dynamics of the homeostatic Process S also show regional specificity. Furthermore, the spatial distribution of SWA is characteristic for an individual and may reflect traits of functional anatomy. The aim of the current study was to quantify inter-individual variation in the parameters of Process S and investigate their spatial distribution. Polysomnographic recordings obtained with 27 EEG derivations of a baseline night of sleep and a recovery night of sleep after 40 h of sustained wakefulness were analyzed. Eight healthy young subjects participated in this study. Process S was modeled by a saturating exponential function during wakefulness and an exponential decline during sleep. Empirical mean SWA per NREM sleep episode at episode midpoint served for parameter estimation at each derivation. Time constants were restricted to a physiologically meaningful range. RESULTS: For both, the buildup and decline of Process S, significant topographic differences were observed: The decline and buildup of Process S were slowest in fronto-central areas while the fastest dynamics were observed in parieto-occipital (decrease) and frontal (buildup) areas. Each individual showed distinct spatial patterns in the parameters of Process S and the parameters differed significantly between individuals. CONCLUSIONS: For the first time, topographical aspects of the buildup of Process S were quantified. Our data provide an additional indication of regional differences in sleep homeostasis and support the notion of local aspects of sleep regulation

Oscillatory patterns in the electroencephalogram at sleep onset

Falling asleep is a gradually unfolding process. We investigated the role of various oscillatory activities including sleep spindles and alpha and delta oscillations at sleep onset (SO) by automatically detecting oscillatory events. We used two datasets of healthy young males, eight with four baseline recordings, and eight with a baseline and recovery sleep after 40 h of sustained wakefulness. We analyzed the 2-min interval before SO (stage 2) and the five consecutive 2-min intervals after SO. The incidence of delta/theta events reached its maximum in the first 2-min episode after SO, while the frequency of them was continuously decreasing from stage 1 onwards, continuing over SO and further into deeper sleep. Interestingly, this decrease of the frequencies of the oscillations were not affected by increased sleep pressure, in contrast to the incidence which increased. We observed an increasing number of alpha events after SO, predominantly frontally, with their prevalence varying strongly across individuals. Sleep spindles started to occur after SO, with first an increasing then a decreasing incidence and a continuous decrease in their frequency. Again, the frequency of the spindles was not altered after sleep deprivation. Oscillatory events revealed derivation dependent aspects. However, these regional aspects were not specific of the process of SO but rather reflect a general sleep related phenomenon. No individual traits of SO features (incidence and frequency of oscillations) and their dynamics were observed. Delta/theta events are important features for the analysis of SO in addition to slow waves

Developmental Changes in Sleep Oscillations during Early Childhood

Although quantitative analysis of the sleep electroencephalogram (EEG) has uncovered important aspects of brain activity during sleep in adolescents and adults, similar findings from preschool-age children remain scarce. This study utilized our time-frequency method to examine sleep oscillations as characteristic features of human sleep EEG. Data were collected from a longitudinal sample of young children (n=8; 3 males) at ages 2, 3, and 5 years. Following sleep stage scoring, we detected and characterized oscillatory events across age and examined how their features corresponded to spectral changes in the sleep EEG. Results indicated a developmental decrease in the incidence of delta and theta oscillations. Spindle oscillations, however, were almost absent at 2 years but pronounced at 5 years. All oscillatory event changes were stronger during light sleep than slow-wave sleep. Large interindividual differences in sleep oscillations and their characteristics (e.g., “ultrafast” spindle-like oscillations, theta oscillation incidence/frequency) also existed. Changes in delta and spindle oscillations across early childhood may indicate early maturation of the thalamocortical system. Our analytic approach holds promise for revealing novel types of sleep oscillatory events that are specific to periods of rapid normal development across the lifespan and during other times of aberrant changes in neurobehavioral function

Disturbance of forest by trampling: Effects on mycorrhizal roots of seedlings and mature trees of Fagus sylvatica

The effects of disturbance by recreational activities (trampling) on changes in soil organic matter (SOM) and on mycorrhizal roots of seedlings and mature trees were studied in four stands of a beech (Fagus sylvatica L.) forest near Basel, Switzerland. At each site, comparable disturbed and undisturbed plots were selected. Disturbance reduced ground cover vegetation and leaf litter. Beech seedlings had lower biomass after disturbance. Ergosterol concentration in seedling roots, an indicator of mycorrhizal fungi, was lower in two of the four disturbed plots compared to undisturbed plots; these two disturbed sites had especially low litter levels. Based on ergosterol measurements, mycorrhizas of mature trees did not appear to be negatively affected by trampling. Total fine roots and SOM were higher in the disturbed than in the undisturbed plots at three sites. At the fourth site, fine roots and SOM in the disturbed areas were lower than in the undisturbed areas most probably due to nutrient input following picnic activities. Principal component analysis revealed a close correlation between SOM and fine roots of mature trees as well as litter and seedling biomass. Trampling due to recreational activities caused considerable damage to the vegetation layer and in particular to the beech seedlings and their mycorrhizal fine roots, whereas, roots of mature trees were apparently resilient to tramplin

Alterations in TRN-anterodorsal thalamocortical circuits affect sleep architecture and homeostatic processes in oxidative stress vulnerable Gclm-/- mice.

Schizophrenia is associated with alterations of sensory integration, cognitive processing and both sleep architecture and sleep oscillations in mouse models and human subjects, possibly through changes in thalamocortical dynamics. Oxidative stress (OxS) damage, including inflammation and the impairment of fast-spiking gamma-aminobutyric acid neurons have been hypothesized as a potential mechanism responsible for the onset and development of schizophrenia. Yet, the link between OxS and perturbation of thalamocortical dynamics and sleep remains unclear. Here, we sought to investigate the effects of OxS on sleep regulation by characterizing the dynamics of thalamocortical networks across sleep-wake states in a mouse model with a genetic deletion of the modifier subunit of glutamate-cysteine ligase (Gclm knockout, KO) using high-density electrophysiology in freely-moving mice. We found that Gcml KO mice exhibited a fragmented sleep architecture and impaired sleep homeostasis responses as revealed by the increased NREM sleep latencies, decreased slow-wave activities and spindle rate after sleep deprivation. These changes were associated with altered bursting activity and firing dynamics of neurons from the thalamic reticularis nucleus, anterior cingulate and anterodorsal thalamus. Administration of N-acetylcysteine (NAC), a clinically relevant antioxidant, rescued the sleep fragmentation and spindle rate through a renormalization of local neuronal dynamics in Gclm KO mice. Collectively, these findings provide novel evidence for a link between OxS and the deficits of frontal TC network dynamics as a possible mechanism underlying sleep abnormalities and impaired homeostatic responses observed in schizophrenia

The Effect of Capsaicin Derivatives on Tight-Junction Integrity and Permeability of Madin-Darby Canine Kidney Cells

Capsaicin is known to interfere with tight junctions (TJs) of epithelial cells and therefore to enhance paracellular permeability of poorly absorbable drugs. However, due to its low water solubility, pungency, and cytotoxicity, its pharmacologic use is limited. In this study, we investigated the effect of capsaicin derivatives of synthetic (e.g., 10-hydroxy-N-(4-hydroxy-3-methoxybenzyl)decanamide, etc.) and natural (olvanil and dihydrocapsaicin) origin on Madin-Darby Canine Kidney–C7 cells. Impedance spectroscopy was used to determine the transepithelial electrical resistance and the capacitance. Permeability assays with fluorescein isothiocyanate–dextran were carried out to evaluate the impact on cell permeability. The results show that lipophilicity could play an important role for the interference with TJ and that the mechanism is independent from the ion channel TRPV-1 and hence on the flux of calcium into the cells. In summary, we synthesized 4 derivatives of capsaicin of lower lipophilicity and compared their properties with other well-known vanilloids. We show that these compounds are able to enhance the permeability of a hydrophilic macromolecule, by opening the TJ for a shorter time than capsaicin. This behavior is dependent on the lipophilicity of the molecule. Understanding of these phenomena may lead to better control of administration of therapeutic molecules

Early alterations in the MCH system link aberrant neuronal activity and sleep disturbances in a mouse model of Alzheimer's disease.

Early Alzheimer's disease (AD) is associated with hippocampal hyperactivity and decreased sleep quality. Here we show that homeostatic mechanisms transiently counteract the increased excitatory drive to CA1 neurons in AppNL-G-F mice, but that this mechanism fails in older mice. Spatial transcriptomics analysis identifies Pmch as part of the adaptive response in AppNL-G-F mice. Pmch encodes melanin-concentrating hormone (MCH), which is produced in sleep-active lateral hypothalamic neurons that project to CA1 and modulate memory. We show that MCH downregulates synaptic transmission, modulates firing rate homeostasis in hippocampal neurons and reverses the increased excitatory drive to CA1 neurons in AppNL-G-F mice. AppNL-G-F mice spend less time in rapid eye movement (REM) sleep. AppNL-G-F mice and individuals with AD show progressive changes in morphology of CA1-projecting MCH axons. Our findings identify the MCH system as vulnerable in early AD and suggest that impaired MCH-system function contributes to aberrant excitatory drive and sleep defects, which can compromise hippocampus-dependent functions

Heritability of Sleep EEG Topography in Adolescence: Results from a Longitudinal Twin Study

The topographic distribution of sleep EEG power is a reflection of brain structure and function. The goal of this study was to examine the degree to which genes contribute to sleep EEG topography during adolescence, a period of brain restructuring and maturation. We recorded high-density sleep EEG in monozygotic (MZ; n = 28) and dizygotic (DZ; n = 22) adolescent twins (mean age = 13.2 ± 1.1 years) at two time points 6 months apart. The topographic distribution of normalized sleep EEG power was examined for the frequency bands delta (1-4.6 Hz) to gamma 2 (34.2-44 Hz) during NREM and REM sleep. We found highest heritability values in the beta band for NREM and REM sleep (0.44 ≤ h2 ≤ 0.57), while environmental factors shared amongst twin siblings accounted for the variance in the delta to sigma bands (0.59 ≤ c2 ≤ 0.83). Given that both genetic and environmental factors are reflected in sleep EEG topography, our results suggest that topography may provide a rich metric by which to understand brain function. Furthermore, the frequency specific parsing of the influence of genetic from environmental factors on topography suggests functionally distinct networks and reveals the mechanisms that shape these networks

Developmental changes in sleep oscillations during early childhood

Although quantitative analysis of the sleep electroencephalogram (EEG) has uncovered important aspects of brain activity during sleep in adolescents and adults, similar findings from preschool-age children remain scarce. This study utilized our time-frequency method to examine sleep oscillations as characteristic features of human sleep EEG. Data were collected from a longitudinal sample of young children (; 3 males) at ages 2, 3, and 5 years. Following sleep stage scoring, we detected and characterized oscillatory events across age and examined how their features corresponded to spectral changes in the sleep EEG. Results indicated a developmental decrease in the incidence of delta and theta oscillations. Spindle oscillations, however, were almost absent at 2 years but pronounced at 5 years. All oscillatory event changes were stronger during light sleep than slow-wave sleep. Large interindividual differences in sleep oscillations and their characteristics (e.g., “ultrafast” spindle-like oscillations, theta oscillation incidence/frequency) also existed. Changes in delta and spindle oscillations across early childhood may indicate early maturation of the thalamocortical system. Our analytic approach holds promise for revealing novel types of sleep oscillatory events that are specific to periods of rapid normal development across the lifespan and during other times of aberrant changes in neurobehavioral function