The maturational trajectories of NREM and REM sleep durations differ across adolescence on both school-night and extended sleep

We recorded sleep electroencephalogram longitudinally across ages 9-18 yr in subjects sleeping at home. Recordings were made twice yearly on 4 consecutive nights: 2 nights with the subjects maintaining their ongoing school-night schedules, and 2 nights with time in bed extended to 12 h. As expected, school-night total sleep time declined with age. This decline was entirely produced by decreasing non-rapid eye movement (NREM) sleep. Rapid eye movement (REM) sleep durations increased slightly but significantly. NREM and REM sleep durations also exhibited different age trajectories when sleep was extended. Both durations exceeded those on school-night schedules. However, the elevated NREM duration did not change with age, whereas REM durations increased significantly. We interpret the adolescent decline in school-night NREM duration in relation to our hypothesis that NREM sleep reverses changes produced in plastic brain systems during waking. The "substrate" produced during waking declines across adolescence, because synaptic elimination decreases the intensity (metabolic rate) of waking brain activity. Declining substrate reduces both NREM intensity (i.e., delta power) and NREM duration. The absence of a decline in REM sleep duration on school-night sleep and its age-dependent increase in extended sleep pose new challenges to understanding its physiological role. Whatever their ultimate explanation, these robust findings demonstrate that the two physiological states of human sleep respond differently to the maturational brain changes of adolescence. Understanding these differences should shed new light on both brain development and the functions of sleep.     

Topographical EEG Mapping in a Case of Recurrent Sleep Terrors

Sleep terrors are characterized by marked CNS arousal and typically occur during stage 3-4 sleep within the first NREM cycle. Studies of the EEG during sleep terrors suggest that delta power and synchrony in the EEG may be important physiological markers of sleep terror presence and intensity. An EEG mapping study was undertaken with a single participant who experienced three sleep terror episodes in the laboratory. A one-minute section of EEG was sampled immediately prior to the onset of each of the three sleep terrors. Similar EEG sections were taken from 10 healthy sex- and age-matched controls. The sleep tenors and control (normative) data were then compared topographically with z-scores (z-mapping). The z-maps indicated that all three sleep terrors contained more total and delta power in central and frontal areas than the control EEG sections. Moreover, relative delta power in these areas for the three sleep terrors was proportional to the subjective intensity of the episode. Although this pre-arousal EEG pattern may be related to ongoing slow-wave sleep mentation that may sometimes trigger sleep terror episodes, its functional significance remains an open question. The results demonstrate the utility of EEG mapping for the quantification of brain activation during sleep terror attacks and suggest that discrete activity profiles are identifiable for different types of dreaming-related arousal.     

Maturation of sleep homeostasis in developing rats: a role for preoptic area neurons

The present study evaluated the hypothesis that developmental changes in hypothalamic sleep-regulatory neuronal circuits contribute to the maturation of sleep homeostasis in rats during the fourth postnatal week. In a longitudinal study, we quantified electrographic measures of sleep during baseline and in response to sleep deprivation (SD) on postnatal days 21/29 (P21/29) and P22/30 (experiment 1). During 24-h baseline recordings on P21, total sleep time (TST) during the light and dark phases did not differ significantly. On P29, TST during the light phase was significantly higher than during the dark phase. Mean duration of non-rapid-eye-movement (NREM) sleep bouts was significantly longer on P29 vs. P21, indicating improved sleep consolidation. On both P22 and P30, rats exhibited increased NREM sleep amounts and NREM electroencephalogram delta power during recovery sleep (RS) compared with baseline. Increased NREM sleep bout length during RS was observed only on P30. In experiment 2, we quantified activity of GABAergic neurons in median preoptic nucleus (MnPN) and ventrolateral preoptic area (VLPO) during SD and RS in separate groups of P22 and P30 rats using c-Fos and glutamic acid decarboxylase (GAD) immunohistochemistry. In P22 rats, numbers of Fos(+)GAD(+) neurons in VLPO did not differ among experimental conditions. In P30 rats, Fos(+)GAD(+) counts in VLPO were elevated during RS. MnPN neuronal activity was state-dependent in P22 rats, but Fos(+)GAD(+) cell counts were higher in P30 rats. These findings support the hypothesis that functional emergence of preoptic sleep-regulatory neurons contributes to the maturation of sleep homeostasis in the developing rat brain.     

The Temporal Structure of Behaviour and Sleep Homeostasis

The amount and architecture of vigilance states are governed by two distinct processes, which occur at different time scales. The first, a slow one, is related to a wake/sleep dependent homeostatic Process S, which occurs on a time scale of hours, and is reflected in the dynamics of NREM sleep EEG slow-wave activity. The second, a fast one, is manifested in a regular alternation of two sleep states – NREM and REM sleep, which occur, in rodents, on a time scale of ∼5–10 minutes. Neither the mechanisms underlying the time constants of these two processes – the slow one and the fast one, nor their functional significance are understood. Notably, both processes are primarily apparent during sleep, while their potential manifestation during wakefulness is obscured by ongoing behaviour. Here, we find, in mice provided with running wheels, that the two sleep processes become clearly apparent also during waking at the level of behavior and brain activity. Specifically, the slow process was manifested in the total duration of waking periods starting from dark onset, while the fast process was apparent in a regular occurrence of running bouts during the waking periods. The dynamics of both processes were stable within individual animals, but showed large interindividual variability. Importantly, the two processes were not independent: the periodic structure of waking behaviour (fast process) appeared to be a strong predictor of the capacity to sustain continuous wakefulness (slow process). The data indicate that the temporal organization of vigilance states on both the fast and the slow time scales may arise from a common neurophysiologic mechanism.     

Sleep and cortical temperature in the Djungarian hamster under baseline conditions and after sleep deprivation

The Djungarian hamster (Phodopus sungorus) is a markedly photoperiodic rodent which exhibits daily torpor under short photoperiod. Normative data were obtained on vigilance states, electroencephalogram (EEG) power spectra (0.25–25.0 Hz), and cortical temperature (T_CRT) under a 168 h light-dark schedule, in 7 Djungarian hamsters for 2 baseline days, 4 h sleep deprivation (SD) and 20 h recovery.During the baseline days total sleep time amounted to 59% of recording time, 67% in the light period and 43% in the dark period. The 4 h SD induced a small increase in the amount of non-rapid eye movement (NREM) sleep and a marked increase in EEG slow-wave activity (SWA; mean power density 0.75–4.0 Hz) within NREM sleep in the first hours of recovery. T_CRT was lower in the light period than in the dark period. It decreased at transitions from either waking or rapid eye movement (REM) sleep to NREM sleep, and increased at the transition from NREM sleep to waking or REM sleep. After SD, T_CRT was lower in all vigilance states.In conclusion, the sleep-wake pattern, EEG spectrum, and time course of T_CRT in the Djungarian hamster are similar to other nocturnal rodents. Also in the Djungarian hamster the time course of SWA seems to reflect a homeostatically regulated process as was formulated in the two-process model of sleep regulation.Abbreviations EEG electroencephalogram - EMG electromyogram - N NREM sleep - NREM non-rapid eye movement - R REM sleep - REM rapid eye movement - SD sleep deprivation - SWA slow-wave activity - T_CRT cortical temperature - TST total sleep time - VS vigilance state - W waking     

The neuronal transition probability (NTP) model for the dynamic progression of non-REM sleep EEG: the role of the suprachiasmatic nucleus

Little attention has gone into linking to its neuronal substrates the dynamic structure of non-rapid-eye-movement (NREM) sleep, defined as the pattern of time-course power in all frequency bands across an entire episode. Using the spectral power time-courses in the sleep electroencephalogram (EEG), we showed in the typical first episode, several moves towards-and-away from deep sleep, each having an identical pattern linking the major frequency bands beta, sigma and delta. The neuronal transition probability model (NTP)--in fitting the data well--successfully explained the pattern as resulting from stochastic transitions of the firing-rates of the thalamically-projecting brainstem-activating neurons, alternating between two steady dynamic-states (towards-and-away from deep sleep) each initiated by a so-far unidentified flip-flop. The aims here are to identify this flip-flop and to demonstrate that the model fits well all NREM episodes, not just the first. Using published data on suprachiasmatic nucleus (SCN) activity we show that the SCN has the information required to provide a threshold-triggered flip-flop for TIMING the towards-and-away alternations, information provided by sleep-relevant feedback to the SCN. NTP then determines the PATTERN of spectral power within each dynamic-state. NTP was fitted to individual NREM episodes 1-4, using data from 30 healthy subjects aged 20-30 years, and the quality of fit for each NREM measured. We show that the model fits well all NREM episodes and the best-fit probability-set is found to be effectively the same in fitting all subject data. The significant model-data agreement, the constant probability parameter and the proposed role of the SCN add considerable strength to the model. With it we link for the first time findings at cellular level and detailed time-course data at EEG level, to give a coherent picture of NREM dynamics over the entire night and over hierarchic brain levels all the way from the SCN to the EEG.     

Experienced Mindfulness Meditators Exhibit Higher Parietal-Occipital EEG Gamma Activity during NREM Sleep

Over the past several years meditation practice has gained increasing attention as a non-pharmacological intervention to provide health related benefits, from promoting general wellness to alleviating the symptoms of a variety of medical conditions. However, the effects of meditation training on brain activity still need to be fully characterized. Sleep provides a unique approach to explore the meditation-related plastic changes in brain function. In this study we performed sleep high-density electroencephalographic (hdEEG) recordings in long-term meditators (LTM) of Buddhist meditation practices (approximately 8700 mean hours of life practice) and meditation naive individuals. We found that LTM had increased parietal-occipital EEG gamma power during NREM sleep. This increase was specific for the gamma range (25–40 Hz), was not related to the level of spontaneous arousal during NREM and was positively correlated with the length of lifetime daily meditation practice. Altogether, these findings indicate that meditation practice produces measurable changes in spontaneous brain activity, and suggest that EEG gamma activity during sleep represents a sensitive measure of the long-lasting, plastic effects of meditative training on brain function.     

The cognitive neuroscience of sleep: neuronal systems,consciousness and learning

Sleep can be addressed across the entire hierarchy of biological organization. We discuss neuronal-network and regional forebrain activity during sleep, and its consequences for consciousness and cognition. Complex interactions in thalamocortical circuits maintain the electroencephalographic oscillations of non-rapid eye movement (NREM) sleep. Functional neuroimaging affords views of the human brain in both NREM and REM sleep, and has informed new concepts of the neural basis of dreaming during REM sleep -- a state that is characterized by illogic, hallucinosis and emotionality compared with waking. Replay of waking neuronal activity during sleep in the rodent hippocampus and in functional images of human brains indicates possible roles for sleep in neuroplasticity. Different forms and stages of learning and memory might benefit from different stages of sleep and be subserved by different forebrain regions.     

The link between cardiac autonomic activity and sleep delta power is altered in men with sleep apnea-hypopnea syndrome

We hypothesize that sleep apnea-hypopnea alters interaction between cardiac vagal modulation and sleep delta EEG. Sleep apnea-hypopnea syndrome (SAHS) is related to cardiovascular complications in men. SAHS patients show higher sympathetic activity than normal subjects. In healthy men, non-rapid eye movement (NREM) sleep is associated with cardiac vagal influence, whereas rapid eye movement (REM) sleep is linked to cardiac sympathetic activity. Interaction between cardiac autonomic modulation and delta sleep EEG is not altered across a life span nor is the delay between appearances of modifications in both signals. Healthy controls, moderate SAHS, and severe SAHS patients were compared across the first three NREM-REM cycles. Spectral analysis was applied to ECG and EEG signals. High frequency (HF) and low frequency (LF) of heart rate variability (HRV), ratio of LF/HF, and normalized (nu) delta power were obtained. A coherency analysis between HF(nu) and delta was performed, as well as a correlation analysis between obstructive apnea index (AI) or hypopnea index (HI) and gain, coherence, or phase shift. HRV components were similar between groups. In each group, HF(nu) was larger during NREM, while LF(nu) predominated across REM and wake stages. Coherence and gain between HF(nu) and delta decreased from controls to severe SAHS patients. In SAHS patients, the delay between modifications in HF(nu) and delta did not differ from zero. AI and HI correlated negatively with coherence, while HI correlated negatively with gain only. Apneas-hypopneas affect the link between cardiac sympathetic and vagal modulation and delta EEG demonstrated by the loss of cardiac autonomic activity fluctuations across shifts in sleep stages. Obstructive apneas and hypopneas alter the interaction between both signals differently.     

Sleep and maturation of eucapnic ventilation and CO2 sensitivity in the premature primate

The effects of sleep state and postnatal maturation on steady-state CO2 sensitivity, "inspiratory drive" (VT/TI), and the inspiratory "duty cycle" (TI/Ttot) were examined in nine unanesthetized premature Macaca nemestrina in the first 3 wk of life. Minute volume (VE) in room air was less in NREM sleep than in the awake state but there were no differences in VE, VT/TI, or TI/Ttot between REM and NREM sleep. VE and VT/TI corrected for body weight increased in REM and NREM sleep with postnatal maturation whereas TI/Ttot did not vary. Concomitant with this increase in room air VE and VT/TI, an increase in CO2 sensitivity (delta V/delta Paco2) with postnatal maturation was documented in NREM sleep. CO2 sensitivity was similar between REM and NREM states at each postnatal age. The increase in VE following inhalation of 2-5% CO2 was mediated by an increase in VT/TI, whereas TI/Ttot remained constant. The differences in the effect of sleep on CO2 sensitivity between neonates and adults are discussed and possible mechanisms for the observed developmental increase in CO2 sensitivity are proposed.     

Sleep EEG spectral analysis in a diurnal rodent:Eutamias sibiricus

1. Sleep was studied in the diurnal rodent Eutamias sibiricus, chronically implanted with EEG and EMG electrodes. Analysis of the distribution of wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep over the 24 h period (LD 12:12) showed that total sleep time was 27.5% of recording time during the 12 h light period and 74.4% during the 12 h dark period. Spectral analysis of the sleep EEG revealed a progressive decay in delta power density in NREM sleep during darkness. Power density of the higher frequencies increased at the end of darkness. Power density of the higher frequencies decreased and that of the lower frequencies increased during light. 2. Analysis of the distribution of vigilance states under three different photoperiods (LD 18:6; 12:12; 6:18) revealed that changes in daylength mainly resulted in a redistribution of sleep and wakefulness over light and darkness. Under long days the percentage of sleep during light was enhanced. The time course of delta power density in NREM sleep was characterized by a long rising part and a short falling part under long days, while a reversed picture emerged under short days. As a consequence, the power density during days. As a consequence, the power density during light was relatively high under long days. 3. After 24 h sleep deprivation by forced activity, no significant changes in the percentages of wakefulness and NREM were observed, whereas REM sleep was slightly enhanced. EEG power density, however, was significantly increased by ca. 50% in the 1.25-10.0 Hz range in the first 3 h of recovery sleep. This increase gradually decayed over the recovery night. 4. The same 24 h sleep deprivation technique led to a ca. 25% increase in oxygen consumption during recovery nights. While the results of the EEG spectral analysis are compatible with the hypothesis that delta power density reflects the 'intensity' of NREM sleep as enhanced by prior wakefulness and reduced by prior sleep, such enhanced sleep depth after sleep deprivation is not associated with reduced energy expenditure as might be anticipated by some energy conservation hypotheses on sleep function.     

Developmental changes in the complexity of the electrocortical activity in foetal sheep.

The foetal sheep brain develops organised sleep states from 115-120 d gestational age (dGA, term 150 dGA) alternating between REM and NREM sleep. We aimed to investigate whether maturation of REM or NREM sleep generating structures leads to the development of distinct sleep states. The electrocorticogram (ECoG) was recorded from five unanaesthetised chronically instrumented foetal sheep in utero and was analysed every 5th day between 115-130 dGA by two different non-linear methods. We calculated a non-linear prediction error which quantifies the causality of the ECoG and applied bispectral analysis which quantifies non-linear interrelations of single frequency components within the ECoG signal. The prediction error during REM sleep was significantly higher than during NREM sleep at each investigated age (P<0.0001) coincidental with poor organisation of the rhythmic pattern in the ECoG during REM sleep. At 115 dGA, organised sleep states defined behaviourally were not developed yet. The prediction error, however, showed already different states of electrocortical activity that were not detectable using power spectral analysis. The prediction error of the premature NREM sleep ECoG decreased significantly during emergence of organised sleep states between 115 and 120 dGA and continued to decrease after the emergence of distinct sleep states (P<0.05). The prediction error of the premature REM sleep ECoG did not change until 120 dGA and began to increase at 125 dGA (P<0.05). Using bispectral analysis, we showed couplings between delta waves (1.5-4 Hz) and frequencies in the range of spindle waves (4-8 and 8-12 Hz) during NREM sleep that became closer during development. The results show that maturation of ECoG synchronisation mediating structures is important for the development of organised sleep states. The further divergence of the prediction error of NREM and REM sleep after development of organised sleep states reveals continuous functional development. Thus, complementary application of non-linear ECoG analysis to power spectral analysis provide new insights in the collective behaviour of the neuronal network during the emergence of sleep states.     

State-Dependent Changes in Auditory Sensory Gating in Different Cortical Areas in Rats

Sensory gating is a process in which the brain’s response to a repetitive stimulus is attenuated; it is thought to contribute to information processing by enabling organisms to filter extraneous sensory inputs from the environment. To date, sensory gating has typically been used to determine whether brain function is impaired, such as in individuals with schizophrenia or addiction. In healthy subjects, sensory gating is sensitive to a subject’s behavioral state, such as acute stress and attention. The cortical response to sensory stimulation significantly decreases during sleep; however, information processing continues throughout sleep, and an auditory evoked potential (AEP) can be elicited by sound. It is not known whether sensory gating changes during sleep. Sleep is a non-uniform process in the whole brain with regional differences in neural activities. Thus, another question arises concerning whether sensory gating changes are uniform in different brain areas from waking to sleep. To address these questions, we used the sound stimuli of a Conditioning-testing paradigm to examine sensory gating during waking, rapid eye movement (REM) sleep and Non-REM (NREM) sleep in different cortical areas in rats. We demonstrated the following: 1. Auditory sensory gating was affected by vigilant states in the frontal and parietal areas but not in the occipital areas. 2. Auditory sensory gating decreased in NREM sleep but not REM sleep from waking in the frontal and parietal areas. 3. The decreased sensory gating in the frontal and parietal areas during NREM sleep was the result of a significant increase in the test sound amplitude.     

EEG Correlates of Dream Recall in Depressed Outpatients and Healthy Controls

The present study explored EEG correlates of dream recall in 17 symptomatic, unmedicated depressed patients and in 19 healthy adults. EEG segments from the last 30 minutes of sleep, from the five minutes following morning awakening, and the absolute difference between sleep and waking EEG were contrasted between the two groups of participants during successful dream recall and during no recall. Period amplitude analysis was used to quantify EEG frequencies. Increased high-frequency beta incidence in the right hemisphere and amplitude in both hemispheres during sleep were associated with dream recall in both patient and control groups. Depressed patients also showed higher delta amplitude in both hemispheres during sleep associated with recall, but this effect did not reach significance. With regard to the changes between sleep and wakefiilness, a smaller change in right hemisphere beta and delta incidence characterized successful recall in healthy controls. By contrast, those with depression showed recall success when the sleep/wake shifts in right hemisphere beta and delta incidence were larger. Recall failure was characterized by small EEG shifts from sleep to wakefulness in the depressed group. The same effects were observed for beta and delta amplitude measures, except that healthy controls showed a large shift in delta amplitude in the sleep-wake transition during successful recall but not during recall failure. Recall in those with depression was associated with a dramatic shift in left hemisphere delta amplitude. These findings provide support for Koukkou and Lehmann's (1983, 1993) state-shift hypothesis of dream recall in healthy controls (except for left hemisphere delta amplitude) but not in the depressed. It appears that in order to recall a dream, depressed patients must undergo larger shifts in brain activity and perhaps a different pattern of reorganization of EEG frequencies than controls. This finding may account for the low rates of recall reported previously in this clinical group.     

A Longitudinal Study: Changes in Cortical Thickness and Surface Area during Pubertal Maturation

Sex hormones have been shown to contribute to the organization and function of the brain during puberty and adolescence. Moreover, it has been suggested that distinct hormone changes in girls versus boys may contribute to the emergence of sex differences in internalizing and externalizing behavior during adolescence. In the current longitudinal study, the influence of within-subject changes in puberty (physical and hormonal) on cortical thickness and surface area was examined across a 2-year span, while controlling for age. Greater increases in Tanner Stage predicted less superior frontal thinning and decreases in precuneus surface area in both sexes. Significant Tanner Stage and sex interactions were also seen, with less right superior temporal thinning in girls but not boys, as well as greater decreases in the right bank of the superior temporal sulcus surface area in boys compared to girls. In addition, within-subject changes in testosterone over the 2-year follow-up period were found to relate to decreases in middle superior frontal surface area in boys, but increases in surface area in girls. Lastly, larger increases in estradiol in girls predicted greater middle temporal lobe thinning. These results show that within-subject physical and hormonal markers of puberty relate to region and sex-specific changes in cortical development across adolescence.     

Interhemispheric EEG asymmetries during unilateral bright-light exposure and subsequent sleep in humans

We tested whether evening exposure to unilateral photic stimulation has repercussions on interhemispheric EEG asymmetries during wakefulness and later sleep. Because light exerts an alerting response in humans, which correlates with a decrease in waking EEG theta/alpha-activity and a reduction in sleep EEG delta activity, we hypothesized that EEG activity in these frequency bands show interhemispheric asymmetries after unilateral bright light (1,500 lux) exposure. A 2-h hemi-field light exposure acutely suppressed occipital EEG alpha activity in the ipsilateral hemisphere activated by light. Subjects felt more alert during bright light than dim light, an effect that was significantly more pronounced during activation of the right than the left visual cortex. During subsequent sleep, occipital EEG activity in the delta and theta range was significantly reduced after activation of the right visual cortex but not after stimulation of the left visual cortex. Furthermore, hemivisual field light exposure was able to shift the left predominance in occipital spindle EEG activity toward the stimulated hemisphere. Time course analysis revealed that this spindle shift remained significant during the first two sleep cycles. Our results reflect rather a hemispheric asymmetry in the alerting action of light than a use-dependent recovery function of sleep in response to the visual stimulation during prior waking. However, the observed shift in the spindle hemispheric dominance in the occipital cortex may still represent subtle local use-dependent recovery functions during sleep in a frequency range different from the delta range.     

Development of the nocturnal sleep electroencephalogram in human infants

The development of nocturnal sleep and the sleep electroencephalogram (EEG) was investigated in a longitudinal study during infancy. All-night polysomnographic recordings were obtained at home at 2 wk and at 2, 4, 6, and 9 mo after birth (analysis of 7 infants). Total sleep time and the percentage of quiet sleep or non-rapid eye movement sleep (QS/NREMS) increased with age, whereas the percentage of active sleep or rapid eye movement sleep (AS/REMS) decreased. Spectral power of the sleep EEG was higher in QS/NREMS than in AS/REMS over a large part of the 0.75- to 25-Hz frequency range. In both QS/NREMS and AS/REMS, EEG power increased with age in the frequency range <10 Hz and >17 Hz. The largest rise occurred between 2 and 6 mo. A salient feature of the QS/NREMS spectrum was the emergence of a peak in the sigma band (12-14 Hz) at 2 mo that corresponded to the appearance of sleep spindles. Between 2 and 9 mo, low-frequency delta activity (0.75-1.75 Hz) showed an alternating pattern with a high level occurring in every other QS/NREMS episode. At 6 mo, sigma activity showed a similar pattern. In contrast, theta activity (6.5-9 Hz) exhibited a monotonic decline over consecutive QS/NREMS episodes, a trend that at 9 mo could be closely approximated by an exponential function. The results suggest that 1) EEG markers of sleep homeostasis appear in the first postnatal months, and 2) sleep homeostasis goes through a period of maturation. Theta activity and not delta activity seems to reflect the dissipation of sleep propensity during infancy.     

Basal forebrain acetylcholine release during REM sleep is significantly greater than during waking

Cholinergic neurons of the basal forebrain supply the neocortex with ACh and play a major role in regulating behavioral arousal and cortical electroencephalographic activation. Cortical ACh release is greatest during waking and rapid eye movement (REM) sleep and reduced during non-REM (NREM) sleep. Loss of basal forebrain cholinergic neurons contributes to sleep disruption and to the cognitive deficits of many neurological disorders. ACh release within the basal forebrain previously has not been quantified during sleep. This study used in vivo microdialysis to test the hypothesis that basal forebrain ACh release varies as a function of sleep and waking. Cats were trained to sleep in a head-stable position, and dialysis samples were collected during polygraphically defined states of waking, NREM sleep, and REM sleep. Results from 22 experiments in four animals demonstrated that means +/- SE ACh release (pmol/10 min) was greatest during REM sleep (0.77 +/- 0.07), intermediate during waking (0.58 +/- 0.03), and lowest during NREM sleep (0.34 +/- 0.01). The finding that, during REM sleep, basal forebrain ACh release is significantly elevated over waking levels suggests a differential role for basal forebrain ACh during REM sleep and waking.     

Sleep-Wake Cycle Dysfunction in the TgCRND8 Mouse Model of Alzheimer’s Disease: From Early to Advanced Pathological Stages

In addition to cognitive decline, individuals affected by Alzheimer’s disease (AD) can experience important neuropsychiatric symptoms including sleep disturbances. We characterized the sleep-wake cycle in the TgCRND8 mouse model of AD, which overexpresses a mutant human form of amyloid precursor protein resulting in high levels of β-amyloid and plaque formation by 3 months of age. Polysomnographic recordings in freely-moving mice were conducted to study sleep-wake cycle architecture at 3, 7 and 11 months of age and corresponding levels of β-amyloid in brain regions regulating sleep-wake states were measured. At all ages, TgCRND8 mice showed increased wakefulness and reduced non-rapid eye movement (NREM) sleep during the resting and active phases. Increased wakefulness in TgCRND8 mice was accompanied by a shift in the waking power spectrum towards fast frequency oscillations in the beta (14-20 Hz) and low gamma range (20-50 Hz). Given the phenotype of hyperarousal observed in TgCRND8 mice, the role of noradrenergic transmission in the promotion of arousal, and previous work reporting an early disruption of the noradrenergic system in TgCRND8, we tested the effects of the alpha-1-adrenoreceptor antagonist, prazosin, on sleep-wake patterns in TgCRND8 and non-transgenic (NTg) mice. We found that a lower dose (2 mg/kg) of prazosin increased NREM sleep in NTg but not in TgCRND8 mice, whereas a higher dose (5 mg/kg) increased NREM sleep in both genotypes, suggesting altered sensitivity to noradrenergic blockade in TgCRND8 mice. Collectively our results demonstrate that amyloidosis in TgCRND8 mice is associated with sleep-wake cycle dysfunction, characterized by hyperarousal, validating this model as a tool towards understanding the relationship between β-amyloid overproduction and disrupted sleep-wake patterns in AD.     

Sex Differences in Regional Body Fat Distribution From Pre‐ to Postpuberty

Few large studies have evaluated the emergence of sexual dimorphism in fat distribution with appropriate adjustment for total body composition. The objective of this study was to determine the timing and magnitude of sex differences in regional adiposity from early childhood to young adulthood. Regional fat distribution was measured using dual‐energy X‐ray absorptiometry (trunk and extremity fat using automatic default regions and waist and hip fat using manual analysis) in 1,009 predominantly white participants aged 5–29 years. Subjects were divided into pre (Tanner stage 1), early (Tanner stages 2–3), late (Tanner stages 4–5), and post (males ≥20 years and females ≥18 years) pubertal groups. Sexual dimorphism in trunk fat (adjusted for extremity fat) was not apparent until late puberty, when females exhibited 17% less (P < 0.001) trunk fat than males. By contrast, sex differences in waist fat (adjusted for hip fat) were apparent at each stage of puberty, the effect being magnified with age, with prepubertal girls having 5% less (P = 0.027) and adult women having 48% less (P < 0.0001) waist fat than males. Girls had considerably more peripheral fat whether measured as extremity or hip fat at each stage. Sex differences in regional adiposity were significantly greater in young adults than in late adolescence. Exclusion of overweight participants did not materially affect the estimates. Sexual dimorphism in fat patterning is apparent even prepubertally with girls having less waist and more hip fat than boys. The magnitude of the sex difference is amplified with maturation, and particularly from late puberty to early adulthood.