Spectral analysis of the sleep electroencephalogram during adolescence

OBJECTIVES: To describe developmental changes of the human sleep electroencephalogram (EEG) during adolescence using EEG spectral analysis and specifically to compare the nocturnal dynamics of slow-wave activity (EEG spectral power 0.6-4.6 Hz, a marker for sleep homeostatic pressure) in prepubertal and mature adolescents. DESIGN: After 10 nights on a fixed 10-hour sleep schedule without daytime naps, participants were studied during a 10-hour baseline night. SETTING: Data were collected in a 4-bed sleep research laboratory. PARTICIPANTS: Eight prepubertal children (pubertal stage Tanner 1; mean age 11.3 years, SD +/- 1.2, 4 boys) and 8 mature adolescents (Tanner 5; mean age 14.1 years, +/- 1.3, 3 boys). INTERVENTIONS: Not applicable. MEASUREMENTS: All-night polysomnography was performed. Sleep stages were scored according to conventional criteria. EEG power spectra (of derivation C3/A2) were calculated using a fast Fourier transform routine. RESULTS: A reduction of non-rapid eye movement (NREM) sleep stage 4 (by 40.1%) and greater amounts of stage 2 sleep (19.7%) were found in mature compared to prepubertal adolescents. NREM sleep EEG power was lower in the frequency ranges < 7 Hz, 11.8 to 12.6 Hz, and 16.2 to 16.8 Hz in mature adolescents. A reduction of rapid eye movement sleep spectral power was present in the frequency ranges < 8.6 Hz and 9.6 to 15 Hz for mature compared to prepubertal adolescents. Slow-wave activity showed identical dynamics within individual NREM sleep episodes and across the night in both developmental groups. CONCLUSIONS: The homeostatic recuperative drive during sleep remains unchanged across puberty. The decline of slow-wave sleep during adolescence may reflect developmental changes of the brain rather than changes of sleep regulatory processes.     

The effects of sleep deprivation in humans: topographical electroencephalogram changes in non‐rapid eye movement (NREM) sleep versus REM sleep

Studies on homeostatic aspects of sleep regulation have been focussed upon non‐rapid eye movement (NREM) sleep, and direct comparisons with regional changes in rapid eye movement (REM) sleep are sparse. To this end, evaluation of electroencephalogram (EEG) changes in recovery sleep after extended waking is the classical approach for increasing homeostatic need. Here, we studied a large sample of 40 healthy subjects, considering a full‐scalp EEG topography during baseline (BSL) and recovery sleep following 40 h of wakefulness (REC). In NREM sleep, the statistical maps of REC versus BSL differences revealed significant fronto‐central increases of power from 0.5 to 11 Hz and decreases from 13 to 15 Hz. In REM sleep, REC versus BSL differences pointed to significant fronto‐central increases in the 0.5–7 Hz and decreases in the 8–11 Hz bands. Moreover, the 12–15 Hz band showed a fronto‐parietal increase and that at 22–24 Hz exhibited a fronto‐central decrease. Hence, the 1–7 Hz range showed significant increases in both NREM sleep and REM sleep, with similar topography. The parallel change of NREM sleep and REM sleep EEG power is related, as confirmed by a correlational analysis, indicating that the increase in frequency of 2–7 Hz possibly subtends a state‐aspecific homeostatic response. On the contrary, sleep deprivation has opposite effects on alpha and sigma activity in both states. In particular, this analysis points to the presence of state‐specific homeostatic mechanisms for NREM sleep, limited to <2 Hz frequencies. In conclusion, REM sleep and NREM sleep seem to share some homeostatic mechanisms in response to sleep deprivation, as indicated mainly by the similar direction and topography of changes in low‐frequency activity.     

Prolonged effects of 24-h total sleep deprivation on sleep and sleep EEG in the rat

Long-term effects of 24-h sleep deprivation (SD) on sleep and sleep EEG were analyzed in male rats during 4 recovery days (Rec). An increase of total sleep time and non-rapid eye-movement (NREM) sleep was present during Rec 1-4, and of REM sleep in Rec 1 and in the dark periods of Rec 2 and 3. After the initial increase of slow-wave activity (SWA, mean EEG power density in the 0.75-4.0 Hz range) in NREM sleep, SWA declined below baseline until Rec 3. Sleep continuity was increased in Rec 1. The persistent effects of SD which are probably due to homeostatic and circadian facets of sleep regulation, must be taken into account in the design of SD studies.     

Regional differences of the sleep electroencephalogram in adolescents

The sleep electroencephalogram (EEG) was recorded from anterior (Fz/Cz) and posterior (Pz/Oz) bipolar derivations in two developmental groups: 20 pre- or early pubertal (Tanner 1/2, mean age 11.4 +/- 1.1 years, 11 boys) and 20 late pubertal or mature adolescents (Tanner 4/5, 14.1 +/- 1.3 years, 8 boys). A sleep-state independent reduction of EEG power over almost the entire frequency range was present in Tanner 4/5 compared with Tanner 1/2 adolescents. Spectral characteristics of the sleep EEG yielded state- and frequency-dependent regional differences that were similar in both developmental groups. Anterior predominance of power in delta and sigma ranges occurred in non-rapid eye movement sleep. Rapid eye movement sleep EEG power was greater in low delta, alpha, and sigma ranges for the posterior derivation and in theta and beta ranges for the anterior derivation. The decay rate of the sleep homeostatic process--reflected by the exponential decline of the 2-Hz EEG power band across the sleep episode--did not differ for derivations or groups. These results indicate that the nocturnal dynamics of sleep homeostasis are independent of derivation and remain stable across puberty.     

Sleep tendency during extended wakefulness: insights into adolescent sleep regulation and behavior

Sleep tendency (latency to sleep onset) was examined during extended waking in prepubertal and mature adolescents to determine whether sleep pressure is lower near bedtime in the latter group. Participants were nine prepubertal (pubertal stage Tanner 1, mean age 11.1 years, SD+/-1.3 years, five males) and 11 pubertally mature adolescents (Tanner 5, 13.9+/-1.2 years, three males). They spent 10 nights at home on an identical fixed 10-h sleep schedule followed by a 36-h constant routine with sleep latency tests at 2-h intervals using standard polysomnography. Saliva was collected to assess dim-light melatonin onset (DLMO) phase. DLMO was earlier in the Tanner 1 (mean clock time=20:33 hours, SD=49 min) than Tanner 5 group (21:29 hours+/-42 min). Sleep latency compared at a 'critical period' spanning 12.5 (20:30 hours clock time) to 18.5 h (02:30 hours) after waking did not differ at 20:30 hours, but was shorter for the Tanner 1 group at 22:30 hours (Tanner 1=9.2+/-6.3 min; Tanner 5=15.7+/-5.8 min), 00:30 hours (Tanner 1=3.6+/-1.7 min; Tanner 5=9.0+/-6.4 min), and 02:30 hours (Tanner 1=2.0+/-1.7 min; Tanner 5=4.3+/-3.2 min; trend). These differences were apparent controlling for circadian phase by partial correlation. Sleep tendency after 14.5, 16.5, and 18.5 h awake was lower in mature versus prepubertal adolescents, supporting our hypothesis that a developmental change of intrinsic sleep-wake regulation may provide physiologically mediated 'permission' for later bedtimes in older adolescents.     

Effects of pinealectomy on baseline sleep and response to sleep deprivation

STUDY OBJECTIVES: We have previously reported that older (24 mo.) Fischer rats manifest a diminished post-sleep deprivation increase in NREM and REM sleep. In order to examine whether this decline reflects an age-related change in pineal function, we are now reporting on baseline and recovery sleep parameters in pinealectomized 3-, 12-, and 24-month old rats following 24 hours of sleep deprivation using the disk-over-water method. DESIGN: Three independent age groups; within each group there were sequential measures of sleep under baseline conditions and during recovery from sleep deprivation. SETTING: The Sleep Research Laboratory at the University of Chicago PARTICIPANTS: 56 male Fisher (F344) rats INTERVENTIONS: 24 hours of total sleep deprivation using the disk-over-water method MEASUREMENTS: Sleep staging of EEG and EMG, and power spectral analysis of the EEG RESULTS: Pinealectomized (pinex) rats did not differ from sham-operated (sham) rats in total sleep, REM sleep, super-modal high-amplitude NREM sleep (HS2), a measure of NREM EEG delta power, or circadian rhythm amplitude. In the pinex rats, there was a modest (2.5%) age-independent increase in NREM sleep (p<0.02). The pinex rats of all ages failed to manifest the increase in NREM sleep during recovery seen in the sham-operated animals (p<0.04). CONCLUSIONS: We found no evidence that altered pineal function is responsible for age-related changes in baseline sleep in the rat. These data also suggest that, independent of age, normal pineal function may be relevant to the ability to generate increased NREM sleep in response to prior sleep deprivation.     

Sleep and EEG spectra in the rabbit under baseline conditions and following sleep deprivation

The 24-hr sleep-wake distribution and power spectra of the electroencephalogram were determined in rabbits that had been implanted with cortical and hippocampal electrodes. A diurnal preference for sleep was observed. The spectral power density in nonrapid eye movement sleep (NREM sleep) of the cortex showed a decreasing trend in most frequencies within the 12-hr light period. In the 12-hr dim period no clear trend was present. Most hippocampal EEG frequencies decreased in NREM sleep in the first two hours of the light period, and thereafter stayed on a constant level. Sleep deprivation elicited the following changes: a prolonged increase of NREM sleep and a short increase of REM sleep; in the cortex, an increase of slow-wave activity (SWA; power density in the 0.25-2.0 Hz frequency band) in NREM sleep, which declined in the course of recovery; an enhancement of slow-wave (1.25-3 Hz) and theta (6.25-7 Hz) activity in REM sleep. The hippocampus showed an increase in NREM sleep power density in almost all frequencies. In REM sleep the hippocampus exhibited an increase in power density in the 6.25-7 Hz and 12.25-13 Hz bands, whereas in the 7.25-8 Hz band the values were below baseline. The results show that SWA in NREM sleep and theta activity in REM sleep are enhanced by sleep deprivation, as has been observed in other mammalian species. The EEG changes in the hippocampus resembled those in the cortex.     

The spectrum of the non‐rapid eye movement sleep electroencephalogram following total sleep deprivation is trait‐like

The sleep electroencephalogram (EEG) spectrum is unique to an individual and stable across multiple baseline recordings. The aim of this study was to examine whether the sleep EEG spectrum exhibits the same stable characteristics after acute total sleep deprivation. Polysomnography (PSG) was recorded in 20 healthy adults across consecutive sleep periods. Three nights of baseline sleep [12 h time in bed (TIB)] following 12 h of wakefulness were interleaved with three nights of recovery sleep (12 h TIB) following 36 h of sustained wakefulness. Spectral analysis of the non‐rapid eye movement (NREM) sleep EEG (C3LM derivation) was used to calculate power in 0.25 Hz frequency bins between 0.75 and 16.0 Hz. Intraclass correlation coefficients (ICCs) were calculated to assess stable individual differences for baseline and recovery night spectra separately and combined. ICCs were high across all frequencies for baseline and recovery and for baseline and recovery combined. These results show that the spectrum of the NREM sleep EEG is substantially different among individuals, highly stable within individuals and robust to an experimental challenge (i.e. sleep deprivation) known to have considerable impact on the NREM sleep EEG. These findings indicate that the NREM sleep EEG represents a trait.     

Challenging sleep homeostasis in narcolepsy-cataplexy: implications for non-REM and REM sleep regulation

STUDY OBJECTIVES: We recently proposed insufficient non-rapid eye movement sleep (NREMS) intensity to contribute to disturbed nocturnal sleep in patients with narcolepsy-cataplexy (NC). To test this hypothesis, we investigated the effect of physiologically intensified NREMS in recovery sleep following sleep deprivation. DESIGN: Nocturnal baseline and recovery sleep architecture, and the sleep electroencephalogram (EEG) before and after 40 hours of sustained wakefulness were compared between 6 drug-free patients with NC (age range: 19-37 years) and 6 individually matched, healthy control subjects (18-43 years). MEASUREMENTS: Sleep and sleep EEG power spectra (C3A2 derivation). The dynamics of the homeostatic Process S were estimated from the time course of slow-wave activity (SWA, spectral power within 0.75-4.5 Hz) across consecutive NREMS episodes. SETTINGS: Sleep research laboratory. RESULTS: In baseline, SWA decreased across consecutive NREMS episodes in patients with NC and control subjects. The build-up of SWA, however, was attenuated in NC in the second episode (P = 0.01) due to a higher number of short wake periods (P = 0.02). Prolonged wakefulness increased initial SWA in both groups (P = 0.003) and normalized the baseline differences between patients and control subjects in the time course of SWA in NREMS. The changed dynamics of SWA in the patients in recovery sleep when compared with baseline were associated with reduced numbers of intermittent wake periods in the first (P = 0.01) and second (P = 0.04) NREMS episodes. All patients, but no control subjects, showed a sleep-onset rapid eye movement period (SOREMP) in both baseline and recovery sleep. Sleep deprivation increased SOREMP duration (P = 0.03). CONCLUSIONS: Increased SWA after sleep deprivation indicates that sleep homeostasis is functional in NC. Increased NREMS intensity in recovery sleep postpones sleep fragmentation, supporting our concept that sleep fragmentation is directly related to insufficient NREMS intensity in NC. The persistence of SOREMP despite enhanced NREMS pressure suggests an abnormal interaction between NREMS and REMS regulatory processes.     

Sleep and EEG spectra in rats recorded via telemetry during surgical recovery

STUDY OBJECTIVE: To determine sleep and EEG spectra in rats during surgical recovery. DESIGN: Sleep, activity, and EEG spectral power were examined in rats via telemetry on days 1, 2, 3, 7, 14, and 15 after implantation surgery. RESULTS: NREM sleep and total sleep were increased on days 1 and 2 compared to later days. REM sleep was decreased on days 2 and 3 compared to days 14 and 15, and activity was decreased on days 1 and 2 compared to later days. EEG power (0.5-5 Hz for NREM and wakefulness, and 5.5-10 Hz for REM and wakefulness) was increased on days 1-3 compared to days 7, 14, and 15. CONCLUSION: The results are discussed in terms of their implications for post-surgery stabilization of sleep and potential relevance for sleep after injury.     

Effects of Modafinil on the Sleep EEG Depend on Val158Met Genotype of COMT

Study Objectives:

Modafinil may promote wakefulness by increasing cerebral dopaminergic neurotransmission, which importantly depends on activity of catechol-O-methyltransferase (COMT) in prefrontal cortex. The effects of modafinil on sleep homeostasis in humans are unknown. Employing a novel sleep-pharmacogenetic approach, we investigated the interaction of modafinil with sleep deprivation to study dopaminergic mechanisms of sleep homeostasis.

Design:

Placebo-controlled, double-blind, randomized crossover study.

Setting:

Sleep laboratory in temporal isolation unit.

Participants:

22 healthy young men (23.4 ± 0.5 years) prospectively enrolled based on genotype of the functional Val158Met polymorphism of COMT (10 Val/Val and 12 Met/Met homozygotes).

Interventions:

2 × 100 mg modafinil and placebo administered at 11 and 23 hours during 40 hours prolonged wakefulness.

Measurements and Results:

Subjective sleepiness and EEG markers of sleep homeostasis in wakefulness and sleep were equally affected by sleep deprivation in Val/Val and Met/Met allele carriers (placebo condition). Modafinil attenuated the evolution of sleepiness and EEG 5-8 Hz activity during sleep deprivation in both genotypes. In contrast to caffeine, modafinil did not reduce EEG slow wave activity (0.75-4.5 Hz) in recovery sleep, yet specifically increased 3.0-6.75 Hz and > 16.75 Hz activity in NREM sleep in the Val/Val genotype of COMT.

Conclusions:

The Val158Met polymorphism of COMT modulates the effects of modafinil on the NREM sleep EEG in recovery sleep after prolonged wakefulness. The sleep EEG changes induced by modafinil markedly differ from those of caffeine, showing that pharmacological interference with dopaminergic and adenosinergic neurotransmission during sleep deprivation differently affects sleep homeostasis.

Citation:

Bodenmann S; Landolt HP. Effects of modafinil on the sleep EEG depend on Val158Met genotype of COMT. SLEEP 2010;33(8):1027-1035.     

Sleep deprivation suppresses the increase of rapid eye movement density across sleep cycles

We investigated the association between rapid eye movement (REM) density (REMd) and electroencephalogram (EEG) activity during non‐rapid eye movement (NREM) and REM sleep, within the re‐assessment, in a large sample of normal subjects, of the reduction of oculomotor activity in REM sleep after total sleep deprivation (SD). Coherently with the hypothesis of a role of homeostatic sleep pressure in influencing REMd, a negative correlation between changes in REMd and slow‐wave activity (SWA) was expected. A further aim of the study was to evaluate if the decreased REMd after SD affects ultradian changes across sleep periods. Fifty normal subjects (29 male and 21 female; mean age = 24.3 ± 2.2 years) were studied for four consecutive days and nights. Sleep recordings were scheduled in the first (adaptation), second (baseline) and fourth night (recovery). After awakening from baseline sleep, a protocol of 40 h SD started at 10:00 hours. Polysomnographic measures, REMd and quantitative EEG activity during NREM and REM sleep of baseline and recovery nights were compared. We found a clear reduction of REMd in the recovery after SD, due to the lack of REMd changes across cycles. Oculomotor changes positively correlated with a decreased power in a specific range of fast sigma activity (14.75–15.25 Hz) in NREM, but not with SWA. REMd changes were also related to EEG power in the 12.75–13.00 Hz range in REM sleep. The present results confirm the oculomotor depression after SD, clarifying that it is explained by the lack of changes in REMd across sleep cycles. The depression of REMd can not simply be related to homeostatic mechanisms, as REMd changes were associated with EEG power changes in a specific range of spindle frequency activity, but not with SWA.     

Is homeostatic sleep regulation under low sleep pressure modified by age?

STUDY OBJECTIVES: We have previously shown that healthy older volunteers react with an attenuated frontal predominance of sleep electroen-cephalogram (EEG) delta activity in response to high sleep pressure. Here, we investigated age-related changes in homeostatic sleep regulation under low sleep pressure conditions, with respect to regional EEG differences and their dynamics. DESIGN: Analysis of the sleep EEG during an 8-hour baseline night, during a 40-hour multiple nap protocol (150 minutes of wakefulness and 75 minutes of sleep) and during the following 8-hour recovery night under constant posture conditions. SETTING: Centre for Chronobiology, Psychiatric University Clinics, Basel, Switzerland PARTICIPANTS: Sixteen young (20-31 years) and 15 older (57-74 years) healthy volunteers INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All-night EEG spectra revealed an increase in spindle activity (13-15.25 Hz) for both age groups, but only in the young did we find a significant decrease of delta activity (0.5-1.25 Hz) in response to low sleep pressure conditions, predominantly in occipital brain regions. However, delta activity during the first non-rapid eye movement (NREM) sleep episode was equally reduced in both age groups. This response lasted significantly longer in the young (across the first 2 NREM sleep episodes) than in the older participants (only the first NREM sleep episode). CONCLUSION: The initial EEG delta response to low sleep pressure was similar in healthy older and young participants. Therefore, age-related sleep deteriorations cannot solely be attributed to alterations in the homeostatic sleep-regulatory system. It is, rather, the interplay of circadian and homeostatic factors of sleep regulation, which is changed with aging.     

Homeostatic behavior of fast Fourier transform power in very low frequency non-rapid eye movement human electroencephalogram

Basic research shows that the physiological and molecular mechanisms of very low frequency (<1 Hz) electroencephalogram (EEG) waves of non-rapid eye movement (NREM) sleep differ from those of the higher (1–4 Hz) delta frequencies. Human studies show that the across-NREM period dynamics of very low frequency and 1–4 Hz EEG also differ. These differences and the reported failure of very low frequency EEG power to increase after a night of total sleep deprivation raise the question of whether very low frequency EEG shows the other homeostatic properties established for higher delta frequencies. Here we tested the relation of very low frequency EEG power density to prior waking duration across a normal day and whether these low frequencies meet another criterion for homeostatic sleep EEG: conservation of power across a late nap and post-nap sleep. Data from 19 young adults recorded in four separate sessions of baseline, daytime nap and post-nap sleep were analyzed. Power density in very low frequency NREM EEG increased linearly when naps were taken later in the day (i.e. were preceded by longer waking durations). In the night following an 18:00 h nap, very low frequency power was reduced by roughly the amount of power in the nap. Thus, very low frequency EEG meets two major homeostatic criteria. We hypothesize that these low frequencies reflect the executive rather than the functional processes by which NREM sleep reverses the effects of waking brain activity.     

Topography of EEG dynamics after sleep deprivation in mice

Several recent results show that sleep and sleep regulation are not only global phenomena encompassing the entire brain, but have local features. It is well established that slow-wave activity [SWA; mean electroencephalographic (EEG) power density in the 0.75-4.0 Hz band] in non-rapid eye movement (NREM) sleep is a function of the prior history of sleep and wakefulness. SWA is thought to reflect the homeostatic component of the two-process model of sleep regulation. According to this model, originally formulated for the rat and later extended to human sleep, the timing and structure of sleep are determined by the interaction of a homeostatic Process S and a circadian process. Our aim was to investigate the dynamics of SWA in the EEG of two brain regions (frontal and occipital cortex) after sleep deprivation (SD) in two of the mice strains most often used in gene targeting. C57BL/6J (n = 9) and 129/Ola (n = 8) were recorded during a 24-h baseline day, 6-h SD, and 18-h recovery. Both derivations showed a significant increase in SWA in NREM sleep after SD in both strains. In the first hour of recovery, SWA was enhanced more in the frontal derivation than in the occipital derivation and showed a faster decline. This difference resulted in a lower value for the time constant for the decrease of SWA in the frontal derivation (frontal: 10.9 +/- 2.1 and 6.8 +/- 0.9 h in Ola and C57, respectively; occipital: 16.6 +/- 2.1 and 14.1 +/- 1.5 h; P < 0.02; for each of the strains; paired t-test). Neither time constant differed significantly between the strains. The subdivision of SWA into a slower and faster band (0.75-2.5 Hz and 2.75-4.0 Hz) further highlighted regional differences in the effect of SD. The lower frequency band had a higher initial value in the frontal derivation than in the occipital derivation in both strains. Moreover, in the higher frequency band a prominent reversal took place so that power in the frontal derivation fell below the occipital values in both strains. Thus our results indicate that there may be differences in the brain in the effects of SD on SWA in mice, suggesting regional differences in the dynamics of the homeostatic component of sleep regulation. The data support the hypothesis that sleep has local, use- or waking-dependent features that are reflected in the EEG, as has been shown for humans and the laboratory rat.     

Sharp and sleepy: evidence for dissociation between sleep pressure and nocturnal performance

While sleep restriction decreases performance, not all individuals are equal with regard to sensitivity to sleep loss. We tested the hypothesis that performance could be independent of sleep pressure as defined by EEG alpha-theta power. Twenty healthy subjects (10 vulnerable and 10 resistant) underwent sleep deprivation for 25 h. Subjects had to rate their sleepiness (Karolinska Sleepiness Scale) and to perform a 10-min psychomotor vigilance task (PVT) every 2 h (20:00-08:00 hours). Sleep pressure was measured by EEG power spectral analysis (alpha-theta band 6.0-9.0 Hz). Initial performance, EEG spectral power and KSS score were equal in both groups (ANOVA, NS). The performance of vulnerable subjects significantly increased during the night (rANOVA, P < 0.01), whereas resistant subjects globally sustained their performance. Homeostatic pressure and subjective sleepiness significantly increased during the night (rANOVA, P < 0.01) identically in both categories (rANOVA, NS). Resistant subjects sustained their reaction time independently of the increase in homeostatic pressure. The phenotypic determinants of vulnerability to extended wakefulness remain unknown.     

Mapping Slow Waves by EEG Topography and Source Localization: Effects of Sleep Deprivation

Slow waves are a salient feature of the electroencephalogram (EEG) during non-rapid eye movement (non-REM) sleep. The aim of this study was to assess the topography of EEG power and the activation of brain structures during slow wave sleep under normal conditions and after sleep deprivation. Sleep EEG recordings during baseline and recovery sleep after 40 h of sustained wakefulness were analyzed (eight healthy young men, 27 channel EEG). Power maps were computed for the first non-REM sleep episode (where sleep pressure is highest) in baseline and recovery sleep, at frequencies between 0.5 and 2 Hz. Power maps had a frontal predominance at all frequencies between 0.5 and 2 Hz. An additional occipital focus of activity was observed below 1 Hz. Power maps?≤?1 Hz were not affected by sleep deprivation, whereas an increase in power was observed in the maps?≥?1.25 Hz. Based on the response to sleep deprivation, low-delta (0.5–1 Hz) and mid-delta activity (1.25–2 Hz) were dissociated. Electrical sources within the cortex of low- and mid-delta activity were estimated using eLORETA. Source localization revealed a predominantly frontal distribution of activity for low-delta and mid-delta activity. Sleep deprivation resulted in an increase in source strength only for mid-delta activity, mainly in parietal and frontal regions. Low-delta activity dominated in occipital and temporal regions and mid-delta activity in limbic and frontal regions independent of the level of sleep pressure. Both, power maps and electrical sources exhibited trait-like aspects.     

Sleep homeostasis and cortical synchronization: II. A local field potential study of sleep slow waves in the rat

STUDY OBJECTIVE: Sleep slow-wave activity (SWA, EEG power between 0.5 and 4.0 Hz) decreases homeostatically in the course of non-rapid eye movement sleep (NREM) sleep. According to a recent hypothesis, the homeostatic decrease of sleep SWA is due to a progressive decrease in the strength of corticocortical connections. This hypothesis was evaluated in a large-scale thalamocortical model, which showed that a decrease in synaptic strength, implemented through a reduction of postsynaptic currents, resulted in lower sleep SWA in simulated local field potentials (LFP). The decrease in SWA was associated with a decreased proportion of high-amplitude slow waves, a decreased slope of the slow waves, and an increase in the number of multipeak waves. Here we tested the model predictions by obtaining LFP recordings from the rat cerebral cortex and comparing conditions of high homeostatic sleep pressure (early sleep) and low homeostatic sleep pressure (late sleep). DESIGN: Intracortical LFP recordings during baseline sleep and after 6 hours of sleep deprivation. SETTING: Basic sleep research laboratory. PATIENTS OR PARTICIPANTS: WKY adult male rats. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Early sleep (sleep at the beginning of the major sleep phase, sleep immediately after sleep deprivation) was associated with (1) high SWA, (2) many large slow waves, (3) steep slope of slow waves, and (4) rare occurrence of multipeak waves. By contrast, late sleep (sleep at the end of the major sleep phase, sleep several hours after the end of sleep deprivation) was associated with (1) low SWA, (2) few high-amplitude slow waves, (3) reduced slope of slow waves, and (4) more frequent multipeak waves. CONCLUSION: In rats, changes in sleep SWA are associated with changes in the amplitude and slope of slow waves, and in the number of multi-peak waves. Such changes in slow-wave parameters are compatible with the hypothesis that average synaptic strength decreases in the course of sleep.     

Altered circadian and homeostatic sleep regulation in prokineticin 2-deficient mice

STUDY OBJECTIVES: Sleep is regulated by circadian and homeostatic processes. Recent studies with mutant mice have indicated that circadian-related genes regulate sleep amount, as well as the timing of sleep. Thus a direct link between circadian and homeostatic regulation of sleep may exist, at least at the molecular level. Prokineticin 2 (PK2), which oscillates daily with high amplitude in the suprachiasmatic nuclei (SCN), has been postulated to be an SCN output molecule. In particular, mice lacking the PK2 gene (PK2-/-) have been shown to display significantly reduced rhythmicity for a variety of circadian physiological and behavioral parameters. We investigated the role of PK2 in sleep regulation. DESIGN: EEG/EMG sleep-wake patterns were recorded in PK2-/- mice and their wild-type littermate controls under baseline and challenged conditions. MEASUREMENTS AND RESULTS: PK2-/- mice exhibited reduced total sleep time under entrained light-dark and constant darkness conditions. The reduced sleep time in PK2-/- mice occurred predominantly during the light period and was entirely due to a decrease in non-rapid eye movement (NREM) sleep time. However, PK2-/- mice showed increased rapid eye movement (REM) sleep time in both light and dark periods. After sleep deprivation, compensatory rebound in NREM sleep, REM sleep, and EEG delta power was attenuated in PK2-/- mice. In addition, PK2-/- mice had an impaired response to sleep disturbance caused by cage change in the light phase. CONCLUSIONS: These results indicate that PK2 plays roles in both circadian and homeostatic regulation of sleep. PK2 may also be involved in maintaining the awake state in the presence of behavioral challenges.     

Hypersynchronous delta waves and somnambulism: brain topography and effect of sleep deprivation

STUDY OBJECTIVES: Hypersynchronous delta activity (HSD) is usually described as several continuous high-voltage delta waves (> or = 150 microV) in the sleep electroencephalogram of somnambulistic patients. However, studies have yielded varied and contradictory results. The goal of the present study was to evaluate HSD over different electroencephalographic derivations during the non-rapid eye movement (NREM) sleep of somnambulistic patients and controls during normal sleep and following 38 hours of sleep deprivation, as well as prior to sleepwalking episodes. DESIGN: N/A. SETTING: Sleep disorders clinic. PATIENTS: Ten adult sleepwalkers and 10 sex- and age-matched control subjects were investigated polysomnographically during a baseline night and following 38 hours of sleep deprivation. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: During normal sleep, sleepwalkers had a significantly higher ratio of HSD over the time spent in stage 2, 3 and 4 on frontal and central derivations when compared with controls. Sleep deprivation resulted in a significant increase in the ratio of the time in HSD over the time in stage 4 on the frontal lead in both groups and on the central lead in controls. There was no evidence for a temporal accumulation of HSD prior to the episodes. CONCLUSIONS: HSD shows a clear frontocentral gradient across all subjects during both baseline and recovery sleep and has relatively low specificity for the diagnosis of NREM parasomnias. Increases in HSD after sleep deprivation may reflect an enhancement of the homeostatic process underlying sleep regulation.