Circadian modulation of sequence learning under high and low sleep pressure conditions

Humans are able to learn complex sequences even without conscious awareness. We have studied the repercussions of circadian phase and sleep pressure on the ability to learn structured sequences using a serial reaction time task (SRT). Sixteen young healthy volunteers were studied in a 40-h "constant posture protocol" under high sleep pressure (i.e. sleep deprivation) and low sleep pressure conditions (i.e. sleep satiation attained by multiple naps). Here we show that learning of different sequence structures improved after multiple naps, in particular after naps that followed the circadian peak of rapid-eye-movement (REM) sleep. This situation following sleep contrasted with the lack of learning without sleep. We have evidenced that the observed amelioration of learning new sequences came about by memorizing short sub-fragments ("chunks") of the sequence train. However, SRT performance did not deteriorate under high sleep pressure, despite the high level of sleepiness. Our data indicate that sequence learning is modulated by circadian phase, and the neurophysiological medium required for this type of learning is related to sleep.     

Non-REM sleep EEG power distribution in fatigue and sleepiness

Objectives

The aim of this study is to contribute to the sleep-related differentiation between daytime fatigue and sleepiness.

Methods

135 subjects presenting with sleep apnea–hypopnea syndrome (SAHS, n = 58) or chronic fatigue syndrome (CFS, n = 52) with respective sleepiness or fatigue complaints and a control group (n = 25) underwent polysomnography and psychometric assessments for fatigue, sleepiness, affective symptoms and perceived sleep quality. Sleep EEG spectral analysis for ultra slow, delta, theta, alpha, sigma and beta power bands was performed on frontal, central and occipital derivations.

Results

Patient groups presented with impaired subjective sleep quality and higher affective symptom intensity. CFS patients presented with highest fatigue and SAHS patients with highest sleepiness levels. All groups showed similar total sleep time. Subject groups mainly differed in sleep efficiency, wake after sleep onset, duration of light sleep (N1, N2) and slow wave sleep, as well as in sleep fragmentation and respiratory disturbance. Relative non-REM sleep power spectra distributions suggest a pattern of power exchange in higher frequency bands at the expense of central ultra slow power in CFS patients during all non-REM stages. In SAHS patients, however, we found an opposite pattern at occipital sites during N1 and N2.

Conclusions

Slow wave activity presents as a crossroad of fatigue and sleepiness with, however, different spectral power band distributions during non-REM sleep. The homeostatic function of sleep might be compromised in CFS patients and could explain why, in contrast to sleepiness, fatigue does not resolve with sleep in these patients. The present findings thus contribute to the differentiation of both phenomena.     

Effect of oleamide on sleep and its relationship to blood pressure, body temperature, and locomotor activity in rats.

Oleamide (cis-9,10-octadecenoamide) is a brain lipid that has recently been isolated from the cerebral fluid of sleep-deprived cats. Intracerebroventricular and intraperitoneal administration of oleamide induces sleep in rats. However, it is unclear whether oleamide's hypnogenic effects are mediated, in part, by its actions on blood pressure and core body temperature. Here we show that systemic administration of oleamide (10 and 20 mg/kg) in rats increased slow-wave sleep 2, without affecting blood pressure and heart rate. In addition, oleamide decreased body temperature and locomotor activity in a dose-dependent manner. These latter effects were not correlated in time with the observed increases in slow-wave sleep. These data suggest that the hypnogenic effects of oleamide are not related to changes in blood pressure, heart rate, or body temperature.     

The frontal predominance in human EEG delta activity after sleep loss decreases with age

Sleep loss has marked and selective effects on brain wave activity during subsequent recovery sleep. The electroencephalogram (EEG) responds to sleep deprivation with a relative increase in power density in the delta and theta range during non-rapid eye movement sleep. We investigated age-related changes of the EEG response to sleep deprivation along the antero-posterior axis (Fz, Cz, Pz, Oz) under constant routine conditions. Both healthy young (20-31 years) and older (57-74 years) participants manifested a significant relative increase in EEG power density in the delta and theta range after 40 h of sleep deprivation, indicating a sustained capacity of the sleep homeostat to respond to sleep loss in ageing. However, the increase in relative EEG delta activity (1.25-3.75 Hz) following sleep deprivation was significantly more pronounced in frontal than parietal brain regions in the young, whereas such a frontal predominance was diminished in the older volunteers. This age-related decrease of frontal delta predominance was most distinct at the beginning of the recovery sleep episode. Furthermore, the dissipation of homeostatic sleep pressure during the recovery night, as indexed by EEG delta activity, exhibited a significantly shallower decline in the older group. Activation of sleep regulatory processes in frontal brain areas by an extension of wakefulness from 16 to 40 h appears to be age-dependent. These findings provide quantitative evidence for the hypothesis that frontal brain regions are particularly vulnerable to the effects of elevated sleep pressure ('prefrontal tiredness') and ageing ('frontal ageing').     

Dynamics of the EEG slow-wave synchronization during sleep

OBJECTIVE: To study the dynamics of spatial synchronization of the slow-wave activity recorded from different scalp electrodes during sleep in healthy normal controls. METHODS: We characterized the different levels of EEG synchronization during sleep (in the 0.25-2.5 Hz band) of five healthy subjects by means of the synchronization likelihood (SL) algorithm and analyzed its long-range temporal correlations by means of the detrended fluctuation analysis (DFA). RESULTS: We found higher levels of interregional synchronization during 'cyclic alternating pattern' (CAP) sleep than during nonCAP with a small but significant difference between its A and B phases. SL during CAP showed fluctuations probably corresponding to the single EEG slow-wave elements. DFA showed the presence of two linear scaling regions in the double-logarithmic plot of the fluctuations of SL level as a function of time scale. This indicates the presence of a characteristic time scale in the underlying dynamics which was very stable among the different subjects (1.23-1.33 s). We also computed the DFA exponent of the two scaling regions; the first, with values approximately 1.5, corresponded to fluctuations with period 0.09-0.75 s and the second, with values approximately 1, corresponded to fluctuations with period 1.5-24.0 s. Only the first exponent showed different values during the different sleep stages. CONCLUSIONS: All these results indicate a different role for each sleep stage and CAP condition in the EEG synchronization processes of sleep which show a complex time structure correlated with its neurophysiological mechanisms. SIGNIFICANCE: Very slow oscillations in spatial EEG synchronization might play a critical role in the long-range temporal EEG correlations during sleep which might be the chain of events responsible for the maintenance and correct complex development of sleep structure during the night.     

EEG sleep studies of insomniacs under flunitrazepam treatment.

This study investigates the effect of flunitrazepam, a new benzodiazepine, on the sleep of insomniac patients under chronic treatment. Polygraphic recordings have shown that this drug decreases not only the activity of the wakefulness system, but also the activity of the synchronizing system of slow-wave sleep. The subjective feeling of improved and sounder sleep seems to be related to a decrease of wakefulness pressure as well as to a decrease of body motoricity, but not with the modification of sleep stages themselves. Flunitrazepam appears to possess some regulatory properties on REM sleep, since this stage is enhanced in patients with an initial low amount of REM sleep and decreased in those having a higher initial REM sleep. Flunitrazepam possesses potent and useful hypnogenic properties in man but does not induce physiological sleep.     

Dynamics of EEG background activity level within quiet sleep in successive cycles in infants

We investigated in infants the emergence of the trends of the EEG synchronization throughout quiet sleep (QS) rank. The night sleep of 3 groups with 6 subjects each (aged respectively 9–18 weeks, 21–47 weeks, and 16–45 years) was recorded. A parameter value reflecting the degree of synchronization of the EEG background activity for successive epochs was computed by automatic analysis. For each QS phase 3 indicators of the dynamics of the time course of the EEG parameter activity were determined: the range (difference between the EEG parameter value at the beginning of the QS episode and that at the trough), the trough latency (after QS onset), and the rate of synchronization (range/trough latency). The range and the trough latency increased with age, whereas the rate of synchronization decreased. The range and the rate of synchronization decreased in the successive cycles, whereas the trough latency increased. These results provide further support for the hypothesis of the early emergence of the process S mechanisms and suggest that the framework of the 2-process model could account also for the development of both the EEG background activity dynamics and the sleep-wake organization.     

On the neurobiology of creativity. Differences in frontal activity between high and low creative subjects

The aim was to investigate the relationship between creativity and hemispheric asymmetry, as measured by regional cerebral blood flow (rCBF). Two groups, each consisting of 12 healthy male subjects, who got either very high or low scores on a creativity test, were pre-selected for the rCBF investigation. rCBF was measured during rest and three verbal tasks: automatic speech (Auto), word fluency (FAS) and uses of objects (Brick). State and trait anxiety inventories were answered after the rCBF measurements. Intelligence tests were also administered. It was predicted that highly creative subjects would show a bilateral frontal activation on the divergent thinking task (Brick), while low creative subjects were expected to have a unilateral increase. Calculations were made of differences in blood flow levels between the FAS and the Brick measurements in the anterior prefrontal, frontotemporal and superior frontal regions. In accordance with our prediction, repeated measure-ANOVAs showed that the creativity groups differed significantly in all three regions. The highly creative group had increases, or unchanged activity, while the low creative group had mainly decreases. The highly creative group had higher trait anxiety than the low creative group. On the intelligence tests the low creative group was superior both on logical-inductive ability and on perceptual speed, while the groups were equal on verbal and spatial tests. The results are discussed in terms of complementary functions of the hemispheres.     

Acetylcholine release, EEG spectral analysis, sleep staging and body temperature studies: a multiparametric approach on freely moving rats

We present a neurochemical, electrophysiological and physiological study on freely moving rats. During 3 days, we have simultaneously monitored acetylcholine (ACh) release in the hippocampus using the microdialysis technique, electroencephalogram (EEG), electromyogram (EMG) and subcutaneous temperature. A spectral analysis of EEG was performed and sleep stages were determined. Energy ratio in the delta (0-4 Hz), slow theta (4-6.5 Hz) and fast theta (6.5-9 Hz) band was calculated. Sleep stages were quantified using an automatic staging method. The circadian cycle of these parameters was observed. Waking, body temperature and ACh release presented synchronized cycles with close acrophases. The relationship between the central cholinergic system and the other parameters is discussed. The influence of handling on the measured parameters, as well as possible artifacts linked to the use of neostigmine in the microdialysis method are considered. Attention was focused on the cholinergic control of EEG theta rhythms.     

Isolating low frequency activity EEG spectrum analysis.

A method for isolating and removing very slow activity from EEG records prior to spectrum computation is presented. This is accomplished by an autoregressive filter whose frequency transfer characteristic can be easily controlled. Examples of spectra computed for various filter parameter values are shown.     

EEG spectral power and sleepiness during 24 h of sustained wakefulness in patients with obstructive sleep apnea syndrome.

OBJECTIVE: This study investigated if obstructive sleep apnea syndrome (OSAS) may be associated with higher activity in different frequency bands of the EEG during a sustained wakefulness paradigm. METHODS: Twelve OSA patients and 8 healthy controls were studied with the Karolinska Drowsiness Test (KDT) and subjective ratings of sleepiness (VAS and KSS) conducted every hour during 24 h of sustained wakefulness. RESULTS: The waking EEG activity, mainly in the low (0.5-7.8 Hz) and fast (12.7-29.2 Hz) frequency band, increased as time awake progressed in both groups but more obviously in OSA patients. A similar pattern was observed for rated sleepiness in both groups. Moreover, VAS ratings of alertness were closely related to the awake theta, fast alpha and beta bands in controls but not in OSA patients. CONCLUSIONS: OSAS was associated with a wake-dependent increase in low (0.5-7.8 Hz) and fast (12.7-29.2 Hz) frequency range activity. Variations in behavioural sleepiness measured by VAS ratings closely reflect most of the waking EEG parameters in controls but not in OSA patients. SIGNIFICANCE: In a sustained wakefulness paradigm, higher activity in delta, theta and beta bands associated with OSAS indicates that OSA patients show marked signs of higher sleepiness and stronger efforts than controls to stay awake, even though they tend to underestimate their sleepiness.     

Effects of caudate nuclei or frontal cortex ablations in cats. II. Sleep-wakefulness, EEG, and motor activity.

The effects of caudate nuclei ablation or frontal cortex removal on the percentages of wakefulness and sleep stages, spontaneous motor activity, and the EEG were studied in cats by means of 24-hr polygraphic recordings for a 6-month period. A significant, permanent, reduction of sleep (particularly REM sleep) and an increase in motor activity were observed in cats with removal of most of the frontal tissue in front of the A22 stereotaxic plane. A similar decrease in sleep was also observed in animals with bilateral, almost total, removal of the caudate nuclei, but this reduction almost fully recovered after the second postlesion month. Motor hyperactivity was more marked in cats with caudate ablations than in cats with frontal ablations and persisted indefinitely. No marked or lasting effects on the EEG were observed. Sham-operated cats and those with unilateral caudate removal behaved like intact cats. It is concluded that both the frontal cortex and the caudate nuclei are parts of a postulated, complex, forebrain system modularing brain stem activating-deactivating central nervous system mechanisms.     

Dynamics of EEG spindle frequency activity during extended sleep in humans: relationship to slow-wave activity and time of day

The dynamics of EEG spindle frequency activity (SFA; spectral power density in the 12.25–15.0 Hz range) and its relationship to slow-wave activity (SWA; 0.75–4.5 Hz) were investigated in long sleep episodes (>12 h). Young healthy men went to bed at either 19:00 h (early sleep; prior waking 36 h, n=9) or 24:00 h (late sleep; prior waking 17 h, n=8). In both nights, SWA in non-rapid-eye-movement sleep (NREMS) decreased over the first three to four 1.5-h intervals and remained at a low level in the subsequent five to six 1.5-h intervals. In contrast, the changes of SFA were more variable and differed between the lower (12.25–13.0 Hz), middle (13.25–14.0 Hz) and higher frequency bin (14.25–15.0 Hz). A pronounced influence of time of day was present in the lower and higher SFA bin, when the dynamics were analyzed with respect to clock time. In both the early and late sleep condition, power density in the lower bin was highest between 2:00 and 5:00 h in the morning and decreased thereafter. In the higher bin, power density was low in the early morning hours and increased as sleep was extended into the daytime hours. The results provide further evidence for a frequency-specific circadian modulation of SFA which becomes more evident at a time when SWA is low.     

MAO activity and EEG sleep in primary depression

Platelet monoamine oxidase (MAO) activity and electroencephalographic (EEG) sleep measures were examined in 56 drug-free hospitalized patients with primary depression as defined by the Research Diagnostic Criteria. The group included 35 females and 21 males with a mean age of 42.6 +/- 1.4 years. Platelet MAO and EEG sleep data were compared for the group as a whole and separately for the unipolar, bipolar, male, and female subgroups. No significant relationships could be demonstrated for the entire group or for the unipolar, male, or female subgroups. However, an inverse relationship between MAO activity and REM sleep percent was noted in the bipolar subgroup (p < 0.02). While changes in REM sleep have been relatively firmly established in primary depression, the relationship of MAO to depression and to REM sleep remains unclear.     

Lesions of nucleus basalis alter ChAT activity and EEG in rat frontal neocortex.

The EEG was recorded from frontal, parietal and visual cortices of sham-operated control rats and rats having ibotenic acid lesions of the nucleus basalis. Recordings were made during a period of rest and during stimulus-evoked desynchronization. Spectral power was determined using a Fast Fourier Transform routine; 3 artifact-free 4 sec epochs of resting activity and two 4 sec epochs of activated EEG were analyzed. Choline acetyltransferase activity (ChAT) was measured in each cortical area and was reduced in lesioned animals an average of 25% in frontal cortex, 19% in the parietal region and 10% in visual cortex. The percent of low frequency activity (1-12 Hz) in the frontal EEG was significantly greater in lesioned animals than in the control group during quiet rest; a significant correlation was found between ChAT activity and power in this band. Desynchronized activity was largely unaffected except for a reduction in 25-31 Hz activity in the frontal cortex of lesioned animals. EEG activity in both the parietal and visual areas was unchanged from control values.     

Unihemispheric enhancement of delta power in human frontal sleep EEG by prolonged wakefulness

EEG power spectra exhibit site-specific and state-related differences in specific frequency bands. In the present study we investigated the effect of total sleep deprivation on sleep EEG topography. Eight healthy, young, right-handed subjects were recorded during baseline sleep and recovery sleep after sleep deprivation. Forty hours of sleep deprivation affected power spectra in all derivations. However, hemispheric asymmetries were observed in the delta range. Sleep deprivation enhanced the anterior predominance of delta activity in the left hemisphere but not in the right one. This effect may reflect a functional asymmetry between the dominant and non-dominant hemisphere. The results provide further evidence for the presence of both global and local aspects of sleep regulation.     

Sleep,sleepiness, sleep disorders and alcohol use and abuse

The study of ethanol's effects on sleep has a long history dating back to the work of Nathaniel Kleitman. This paper reviews the extensive literature describing ethanol's effects on the sleep of healthy normals and alcoholics and the newer literature that describes its interactive effects on daytime sleepiness, physiological functions during sleep, and sleep disorders. Ethanol initially improves sleep in non-alcoholics at both low and high doses with disturbance in the second half of the night sleep at high doses. Tolerance develops to the initial beneficial effects. In alcoholics sleep is disturbed both while drinking and for months of abstinence and the nature of the abstinent sleep disturbance is predictive of relapse. Ethanol interacts to exacerbate daytime sleepiness and sleep-disordered breathing, even inducing apnea in persons at risk. Ethanol's effects on other physiological functions during sleep and other sleep disorders has yet to be documented. 2001 Harcourt Publishers Ltd     

Alpha activity in the human REM sleep EEG: topography and effect of REM sleep deprivation.

The topographical distribution of alpha activity (8.125-11.125 Hz) in the REM sleep EEG, its time course within and across REM sleep episodes, and the effects of selective REM sleep deprivation were investigated in 8 young males. Power spectra of bipolar derivations along the antero-posterior axis in the left (F3C3, C3P3, P301) and right (F4C4, C4P4, P402) hemisphere were calculated. Alpha activity increased along the antero-posterior axis in both hemispheres, and was dominant in the right hemisphere. It decreased within and across REM sleep episodes. Selective REM sleep deprivation resulted in a reduction of alpha activity in the REM sleep EEG. However, the topographical distribution and the time course were not affected. It is suggested that alpha activity in the REM sleep EEG is a marker of REM sleep homeostasis.     

Longitudinal sleep EEG, temperature, and activity measurements across the menstrual cycle in patients with premenstrual depression and in age-matched controls

After a 2-month evaluation period, eight women with moderate to severe premenstrual depression and eight age- and sex-matched controls underwent sleep electroencephalographic (EEG) and temperature recordings 2 nights a week over the course of one menstrual cycle. Overall, patients had more Stage 2 (%) sleep and less rapid eye movement (REM) sleep (% and minutes) than normal controls. Stage 3 sleep and number of intermittent awakenings varied with phases of the menstrual cycle. Temperature minima were earlier in patients compared with controls, but this difference was not statistically significant, and there was no significant effect of menstrual cycle phase on the timing of temperature minima. Wrist motor activity did not change during the menstrual cycle in patients or controls. Thus, in this sample of women with premenstrual depression, we did not find sleep EEG alterations similar to those reported in some patients with major depressive disorder. In light of the small number of subjects and the large individual variability, the absence of marked changes with the menstrual cycle may be a function of a Type II error.