Regional differences in the dynamics of the cortical EEG in the rat after sleep deprivation.

OBJECTIVE: To investigate regional changes of the cortical sleep EEG in the rat, recordings were obtained from a frontal and an occipital derivation, on a baseline day (n = 14 male rats, Sprague-Dawley strain) and after 24 h sleep deprivation (SD, n = 7). METHODS: Spectral analysis of the vigilance states revealed state and frequency specific differences in EEG power by two-way ANOVA and post-hoc t tests. RESULTS: In the theta band (6.25-9.0 Hz) occipital power was larger than frontal power in waking and REM sleep, whereas frontal power was larger in the frequency range between 10.25-16.0 Hz in non-REM sleep and REM sleep. After SD frontal power in the 2-4 Hz band in non-REM sleep was increased more than occipital power and frontal power in the 10.25-16.0 Hz range was more attenuated. In REM sleep frontal power in the theta band and in the 10.25-16.0 Hz range was more increased than occipital power. Power in the waking EEG did not differ between the two derivations after SD. CONCLUSIONS: The differential responses to SD may reflect regional use-dependent aspects of sleep regulation. These observations support the notion that sleep is not only a global phenomenon but has also local, use-dependent features.     

Homeostatic sleep regulation is preserved in mPer1 and mPer2 mutant mice

A limited set of genes, Clock, Bmal1, mPer1, mPer2, mCry1 and mCry2, has been shown to be essential for the generation of circadian rhythms in mammals. It has been recently suggested that circadian genes might be involved in sleep regulation. We investigated the role of mPer1 and mPer2 genes in the homeostatic regulation of sleep by comparing sleep of mice lacking mPER1 (mPer1 mutants) or a functional mPER2 (mPer2 mutants), and wild-type controls (WT) after 6 h of sleep deprivation (SD). Our main result showed that after SD, all mice displayed the typical increase of slow-wave activity (SWA; EEG power density between 0.75 and 4 Hz) in nonREM sleep, reflecting the homeostatic response to SD. This increase was more prominent over the frontal cortex as compared to the occipital cortex. The genotypes did not differ in the effect of SD on the occipital EEG, while the effect on the frontal EEG was initially diminished in both mPer mutants. Differences between the genotypes were seen in the 24-h distribution of sleep, reflecting especially the phase advance of motor activity onset observed in mPer2 mutants. While the daily distribution of sleep was modulated by mPer1 and mPer2 genes, sleep homeostasis reflected by the SWA increase after 6-h SD was preserved in the mPer mutants. The results provide further evidence for the independence of the circadian and the homeostatic components underlying sleep regulation.     

Sleep deprivation in prion protein deficient mice sleep deprivation in prion protein deficient mice and control mice: genotype dependent regional rebound

We have previously reported a larger and more prolonged increase of slow wave activity (SWA) in NREM sleep after sleep deprivation (SD) in prion protein deficient mice (PrP) compared to wild-type mice. Regional differences in the SWA increase were investigated by comparing the effect of 6 h SD on a frontal and occipital derivation in PrP deficient mice and wild-type mice. The larger increase of SWA after SD in PrP deficient mice was restricted to the occipital derivation. The difference appeared after the waking-NREM sleep transitions, making it unlikely that PrP is involved in the mechanisms enabling the transition to sleep. Our findings may reflect differences between the genotypes in the need for recovery in this particular brain region.     

Sleep states and sleep electroencephalographic spectral power in mice lacking the beta 3 subunit of the GABA(A) receptor

Mice lacking the GABA(A) receptor beta(3) subunit exhibit a profound disruption in thalamic circuitry. We have studied sleep in these mice under baseline conditions and following treatment with the benzodiazepine midazolam. Under baseline conditions, NREM sleep time did not differ between beta(3) subunit knockout mice and wild type mice, while REM sleep time was significantly lower in knockout mice than in wild type mice during the light portion of a 24-h light-dark cycle. In constant dark conditions, circadian rhythmicity remained intact in mutant mice for a period of at least 9 days. EEG delta power (1-4 Hz) was significantly greater in the knockout than in wild type mice during NREM sleep but not during other states. A transient increase in EEG power in the 12-16 Hz range that occurred in wild type mice just prior to the transition from NREM to REM sleep was present but significantly blunted in the knockout. Midazolam decreased NREM delta power and REM time in wild type mice. The former but not the latter response to midazolam was intact in the knockout. These results further support a role for GABAergic transmission in regulating REM sleep and EEG spectral phenomena associated with NREM sleep.     

The EEG effects of THIP (Gaboxadol) on sleep and waking are mediated by the GABA(A)delta-subunit-containing receptors

THIP (4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol, Gaboxadol) is a selective gamma-aminobutyric acid (GABA)(A) agonist, acting in vitro with high potency and efficacy at the extrasynaptic GABA(A)delta-containing receptors. THIP was suggested to be a potential hypnotic to treat insomnia, and it is currently in clinical trial. Here we assessed whether the GABA(A)delta-containing receptors mediate in vivo the effect of THIP on sleep and the sleep electroencephalogram (EEG). We performed EEG recordings in a mouse model deficient in the GABA(A)delta-subunit gene (delta(-/-) mice) and in wild-type littermate controls. THIP (4 and 6 mg/kg intraperitoneally) induced an abnormal EEG pattern, resulting in dramatic changes in the waking and non-rapid eye movement (NREM) sleep EEG spectra in wild-type mice. Indeed, a massive increase in EEG power lasting 2-3 h occurred in both the frontal and parietal derivation, especially in frequencies below 6 Hz. All effects were more prominent in the frontal EEG. Furthermore, the highest dose of THIP lengthened REM sleep latency and suppressed REM sleep. In contrast, vigilance states and sleep latencies were not affected in delta(-/-) mice. Moreover, only minor changes were observed in the NREM sleep EEG spectrum after THIP injection in the delta-subunit-deficient mice. The present findings do not indicate a sleep-promoting effect of THIP in mice, which is in accordance with a previous report in this species. Moreover, our results in vivo demonstrate that THIP acts preferentially at GABA(A) receptors containing the delta-subunit.     

Sleep slow wave changes during the middle years of life

Slow waves (SW; < 4 Hz and > 75 μV) during non-rapid eye movement (NREM) sleep in humans are characterized by hyperpolarization [surface electroencephalogram (EEG) SW negative phase], during which cortical neurons are silent, and depolarization (surface EEG positive phase), during which the cortical neurons fire intensively. We assessed the effects of age, sex and topography on the dynamics of SW characteristics in a large population (n=87) of healthy young (23.3 ± 2.4 years) and middle-aged (51.9 ± 4.6 years) volunteers. Older subjects showed lower SW density and amplitude than young subjects. Age-related lower SW density in men was especially marked in prefrontal/frontal brain areas, where they originate more frequently. Older subjects also showed longer SW positive and negative phase durations. These last results indicate that, in young subjects, cortical neurons would synchronously enter the SW hyperpolarization and depolarization phases, whereas this process would take longer in older subjects, leading to lower slope and longer SW positive and negative phases. Importantly, after controlling for SW amplitude, middle-aged subjects still showed lower slope than young subjects in prefrontal, frontal, parietal and occipital derivations. Age-related effects on SW density, frequency and positive phase duration were more prominent at the beginning of the night, when homeostatic sleep pressure is at its highest. Age-related SW changes may be associated with changes in synaptic density and white matter integrity and may underlie greater sleep fragmentation and difficulty in recuperating and maintaining sleep under challenges in older subjects.     

Sleep homeostasis in the rat in the light and dark period

Sleep is regulated by the interaction of a homeostatic (Process S) and a circadian component. The duration of prior wakefulness is the main factor influencing subsequent sleep duration and its intensity. We investigated in the rat whether the sleep-wake history before sleep deprivation (SD) contributes to the effects of sleep loss incurred during the SD. A 24-h baseline recording was followed by 6 h SD at light onset (SD-Light, n=7), or at dark onset (SD-Dark, n=8) and 18 h recovery. Both SDs led to a pronounced increase in slow wave activity (SWA, EEG power between 0.75 and 4.0 Hz) in NREM sleep and increased sleep consolidation. The prolongation of sleep episodes was associated with increased intra-episode SWA. The amount of waking before the SD correlated positively with the SWA increase during recovery, and SWA levels before SD were negatively correlated with their subsequent increase. The time-course of SWA (Process S) as well as of single frequency bins within the SWA band was successfully simulated based on vigilance-state distribution. The time constant of the exponential monotonic decay (Td) was higher for the 0.75-1.0 Hz bin compared to all remaining frequency bins of the SWA band, reflecting a slower process determining the slow EEG component during sleep. The data show that the homeostatic response after SD, consisting of increased sleep intensity and sleep consolidation is determined by a combination of SD and the preceding vigilance-state history. The slower dynamics of low frequency delta power compared to fast delta frequencies point to heterogeneity within the traditionally defined SWA band.     

Reduced fronto-cortical brain connectivity during NREM sleep in Asperger syndrome: An EEG spectral and phase coherence study

Objective

To investigate whether sleep macrostructure and EEG power spectral density and coherence during NREM sleep are different in Asperger syndrome (AS) compared to typically developing children and adolescents.

Methods

Standard all night EEG sleep parameters were obtained from 18 un-medicated subjects with AS and 14 controls (age range: 7.5–21.5 years) after one adaptation night. Spectral, and phase coherence measures were computed for multiple frequency bands during NREM sleep.

Results

Sleep latency and wake after sleep onset were increased in AS. Absolute power spectrum density (PSD) was significantly reduced in AS in the alpha, sigma, beta and gamma bands and in all 10 EEG derivations. Relative PSD showed a significant increase in delta and a decrease in the sigma band for frontal, and in beta for centro-temporal derivations. Intrahemispheric coherence measures were markedly lower in AS in the frontal areas, and the right hemisphere over all EEG channels. The most prominent reduction in intrahemispheric coherence was observed over the fronto-central areas in delta, theta, alpha and sigma EEG frequency bands.

Conclusion

EEG power spectra and coherence during NREM sleep, in particular in fronto-cortical derivations are different in AS compared to typically developing children and adolescents.

Significance

Quantitative analysis of the EEG during NREM sleep supports the hypothesis of frontal dysfunction in AS.     

Coherent neocortical 40‐Hz oscillations are not present during REM sleep

During cognitive processes there are extensive interactions between various regions of the cerebral cortex. Oscillations in the gamma frequency band (≈40 Hz) of the electroencephalogram (EEG) are involved in the binding of spatially separated but temporally correlated neural events, which results in a unified perceptual experience. The extent of these interactions can be examined by means of a mathematical algorithm called ‘coherence’, which reflects the ‘strength’ of functional interactions between cortical areas. The present study was conducted to analyse EEG coherence in the gamma frequency band of the cat during alert wakefulness (AW), quiet wakefulness (QW), non‐rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. Cats were implanted with electrodes in the frontal, parietal and occipital cortices to monitor EEG activity. Coherence values within the gamma frequency (30–100 Hz) from pairs of EEG recordings were analysed. A large increase in coherence occurred between all cortical regions in the 30–45 Hz frequency band during AW compared with the other behavioral states. As the animal transitioned from AW to QW and from QW to NREM sleep, coherence decreased to a moderate level. Remarkably, there was practically no EEG coherence in the entire gamma band spectrum (30–100 Hz) during REM sleep. We conclude that functional interactions between cortical areas are radically different during sleep compared with wakefulness. The virtual absence of gamma frequency coherence during REM sleep may underlie the unique cognitive processing that occurs during dreams, which is principally a REM sleep‐related phenomenon.     

Sleep homeostasis in the female rat during the estrous cycle

To investigate whether sleep homeostasis in the female rat is modulated by the estrous cycle, the vigilance states, EEG power spectra and cortical temperature (T_CRT) were assessed on the basis of 4-day continuous recordings. A regulatory response was elicited by 6-h sleep deprivation (SD) during the proestrous (PRO) and the estrous (EST) day and compared to the baseline recordings. The vigilance states varied across the estrous cycle. In the PRO dark period the amount of sleep was reduced. The decrease in rapid-eye-movement (REM) sleep was already evident towards the end of the preceding light period, and an increased fragmentation of sleep was present throughout PRO. Compared to the other days of the estrous cycle, slow-wave activity (SWA; EEG power density 0.75–4.75 Hz) in nonREM (NREM) sleep was lower in PRO at the end of the light period and in the beginning of the dark period. High-frequency activity (HFA; EEG power density 10.25–25.0 Hz) was increased in the dark period of PRO. The SD performed during the first 6 h of the light period of PRO and EST enhanced SWA in NREM sleep and reduced sleep fragmentation during the subsequent 6 h. The extent and time course of the response to SD did not differ between the two phases of the estrous cycle. It is concluded that despite the marked baseline variations of the vigilance states and the EEG, homeostatic regulation is little affected by the estrous cycle.     

Relationship of sleep interictal epileptiform discharges to sigma activity (12-16 Hz) in benign epilepsy of childhood with rolandic spikes.

OBJECTIVE: The activation of interictal epileptic discharges (IEDs) by NREM sleep is a well-known phenomenon in benign epilepsy of childhood with rolandic spikes (BECRS). The activating properties of NREM sleep on IEDs have been attributed to increased synchronization within thalamocortical neurons. During NREM sleep two synchronizing mechanisms lead to the appearance of spindles and delta waves on the EEG. Spectral analysis technique is a suitable method that can be used to quantitatively describe the dynamics of delta (slow wave activity (SWA) 0.5-4.0 Hz) and sigma activity (12.0-16.0 Hz) during sleep. METHODS: In order to define more accurately the relationship between synchronizing mechanisms (spindles and delta activities) and IEDs during sleep in BECRS, we have performed overnight continuous EEG polysomnography studies in 9 patients (mean age 7.4 +/- 2.5 years). The temporal series of SWA and sigma values, derived from spectral analysis, have been obtained from a spike-free derivation lead. The IEDs count has been performed on the most active lead. Relationships between sigma and SWA and time series of IEDs were tested by means of correlation techniques after data normalization. RESULTS: Our results revealed a significant higher correlation between IEDs and sigma activity with respect to SWA in all the subjects, in total sleep time. The same analysis limited to NREM sleep highlights the better correlation between sigma and IEDs. CONCLUSIONS: Data suggest that during sleep of BECRS patients, IEDs are more sensitive to the promoting action of the spindle-generating mechanism than to the SWA-producing one.     

T-type calcium channels and thalamocortical rhythms in sleep: a perspective from studies of T-type calcium channel knockout mice

Sleep is characterized by synchronized electrical activities of the thalamocortical network, which can be identified as the EEG oscillations during sleep. T-type calcium channels have been implicated in the occurrence of sleep waves, and burst firings in the thalamic neurons driven by these channels are known to be essential for modulation of sleep rhythms. Studies showed that alpha1(G) T-type calcium channel knockout mice had defects in sleep waves such as lack of delta oscillations (1-4 Hz) and alteration of sleep spindles (7-15 Hz), which are known to be modulated by T-currents in the thalamus. The mutation also affected the sleep-wake transition, thus resulting in decreased NREM sleep and increased sleep disturbance. These findings support the idea that alpha1(G) T-type calcium channels contribute to sleep waves as well as to behavioral state of sleep.     

The sleep EEG's microstructure in depression: alterations of the phase relations between EEG rhythms during REM and NREM sleep

OBJECTIVE: We investigated the microstructure of sleep electroencephalograms (EEGs) of 13 unmedicated depressive inpatients and 13 healthy controls matched in sex and age, hypothesizing that depressives depict an alteration of certain EEG oscillations across the night. METHODS: We digitized the sleep EEGs with a sampling rate of 100 Hz (bipolar derivation C(z)-P(z), 1440 single sweeps; 2048 data points each), calculated the time course of delta (1-3.5 Hz), theta (3.5-7.5 Hz), alpha (7.5-15 Hz), and beta (15-35 Hz) activity over the night, and determined the correlation coefficients of these different EEG rhythms separately for rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. RESULTS: For both groups we detected a clear difference between REM and NREM sleep cycles at certain frequency bands. The most impressive changes occurred for the delta/beta and theta/beta correlations, which change their signs between NREM (negatively correlated) and REM (positively correlated) sleep cycles. Following an analysis of variance model with repeated measurement design, a statistically significant group effect (P=0.024) between depressives and controls was observable during NREM sleep for the delta/beta (P=0.010) and theta/beta (P=0.018) interactions. CONCLUSION: We detected alterations of certain sleep EEG oscillations during the NREM sleep cycle, where the delta/beta as well as the theta/beta activities were higher (negatively) compared to healthy controls. Together with previous investigations on the influence of antidepressants on the microstructure of sleep EEGs, this is another hint that the NREM sleep cycle plays a major role in depression.     

Difference in sleep regulation between morning and evening circadian types as indexed by antero-posterior analyses of the sleep EEG

Circadian types classify individuals according to their preferred timing for activity and sleep, morning and evening types showing, respectively, early or late preferences. This characteristic has been associated with corresponding differences in circadian sleep propensity. In this study, quantitative analysis of the sleep EEG in antero-posterior derivations was used to test the hypothesis that morning and evening types differ not only in the circadian aspect of sleep regulation but also in the homeostatic aspect. Morning types and evening types (six men and six women per group, aged 19-34 years) were selected using the Morningness-Eveningness Questionnaire. They were studied by polysomnography according to their preferred sleep schedule. Spectral activity in four midline derivations (Fz, Cz, Pz, Oz) was calculated separately in nonrapid eye movement (NREM) sleep and in rapid eye movement (REM) sleep. In NREM sleep, morning types showed a steeper decrease of slow-wave activity (SWA; 1-5 Hz) per sleep cycle in the fronto-central derivations and a steeper increase in 13-14 Hz activity in the parieto-occipital derivations than did evening types. Nonlinear regression analysis revealed that the exponential decay rate of relative values of SWA in NREM sleep was faster in morning than evening types, in the frontal derivation. In REM sleep, morning types showed a steeper decrease of high sigma (14-16 Hz) and beta (16-24 Hz) activities across the night in centro-parietal derivations than did evening types. These results show for the first time a clear difference between morning types and evening types in homeostatic sleep regulation.     

Topographical distribution of delta rhythms during sleep: evolution with age

This study concerns the evolution of slow EEG activities (delta rhythms) and their topographical distribution during 31 night sleep records of 27 control subjects whose ages ranged from 1 month to 27 years. A system of data processing allows the representation of continuous changes in 8 derivations of the power of 0.5--4.5 c/sec waves. The obtained curves, whose respective magnitudes depend on the chosen montage, parallel the sleep cycles of the classical hypnogram. They do not clearly differentiate NREM sleep stages, but show a progressive increase of delta rhythm power with the deepening of NREM sleep. Moreover, measurement of the magnitude to these curves allows comparisons between the different channels in a given record and between different recordings. With the referential setting used in this study the topographical organization of the occipital, parietal and central curves proved occipital, parietal and central curves proved remarkably consistent in all subjects. The general magnitude of these curves decreased with age while that of frontal curves slightly increased. The right parietal curves were of greater magnitude than the left in every record obtained from children aged 2--5 years. The changes with age, and the intra- and interindividual differences are discussed. The data suggest hypotheses about the importance of NREM sleep in developmental processes.     

Human sleep spindle characteristics after sleep deprivation

OBJECTIVE: Sleep spindles (12-15 Hz oscillations) are one of the hallmarks of the electroencephalogram (EEG) during human non-rapid eye movement (non-REM) sleep. The effect of a 40 h sleep deprivation (SD) on spindle characteristics along the antero-posterior axis was investigated. METHODS: EEGs during non-REM sleep in healthy young volunteers were analyzed with a new method for instantaneous spectral analysis, based on the fast time frequency transform (FTFT), which yields high-resolution spindle parameters in the combined time and frequency domain. RESULTS: FTFT revealed that after SD, mean spindle amplitude was enhanced, while spindle density was reduced. The reduction in spindle density was most prominent in the frontal derivation (Fz), while spindle amplitude was increased in all derivations except in Fz. Mean spindle frequency and its variability within a spindle were reduced after SD. When analyzed per 0.25 Hz frequency bin, amplitude was increased in the lower spindle frequency range (12-13.75 Hz), whereas density was reduced in the high spindle frequency range (13.5-14.75 Hz). CONCLUSIONS: The observed reduction in spindle density after SD confirms the inverse homeostatic relationship between sleep spindles and slow waves whereas the increase in spindle amplitude and the reduction in intra-spindle frequency variability support the hypothesis of a higher level of synchronization in thalamocortical cells when homeostatic sleep pressure is enhanced.     

Effects of circadian phase and duration of sleep deprivation on sleep and EEG power spectra in the cat

The electroencephalogram (EEG) of cats was recorded under baseline conditions (LD 12:12) and after 4 and 8 h of sleep deprivation (SD). The EEG was analyzed by visual scoring and by spectral analysis. Under baseline conditions the 24-h distribution of sleep was bimodal: the smallest amounts of sleep occurred at the light-dark and dark-light transitions. EEG slow-wave activity (power density in the delta frequency range: 0.5-4.0 Hz) in non-rapid-eye-movement sleep (NREMS) showed a small variation over the 24-h period. When recovery sleep, following 4 h and 8 h of SD, started at the beginning of the dark period, no significant rebound of NREMS and REMS occurred during the 24-h recovery period. When recovery sleep, after 4 h of SD, started at the fifth hour of the light period, the amount of NREMS was increased. In all experiments the EEG power density in NREMS was enhanced after SD in the entire frequency range studied (0.5-31.5 Hz), but more prominently in the delta and theta (4.5-7.0 Hz) frequency bands. The effects dissipated in the course of the recovery period. The magnitude and duration of the enhancements of EEG power densities were dependent on the duration of SD and on the circadian phase at which SD was scheduled. It is concluded that in the cat sleep is a function of both circadian and homeostatic processes and that especially the EEG power density in NREMS is highly responsive to sleep loss.     

Poverty,cultural disadvantage and brain development: a study of pre-school children in Mexico

Forty-two children, who had been studied previously at the age of 18–30 months, were studied again at 4 years of age. Twenty-two belonged to low socioeconomic strata and were classified as high-risk children (HRC) the other 20 were classified as low-risk children (LRC), and belonged to middle and middle-high socioeconomic strata. Ten minutes of EEG using reference derivations (with linked earlobes) were recorded from each subject. Twenty EEG segments of 3.2 s each were selected by visual inspection for Fourier analysis. Absolute power (AP) was computed for the total EEG energy (1.5–19 Hz) as well as each reference derivation in 4 frequency bands: delta (1.5–3.5Hz), theta (4–7.5 Hz), alpha (7.5–12.5 Hz) and beta (12.5–19Hz). HRC had significantly more delta AP than LRC in frontal and central leads, and higher values of theta AP in frontal leads. Alpha AP was higher in LRC in occipital areas and in F8 and T4. This study suggests a maturational lag in HRC.     

The effect of 3-h and 6-h sleep deprivation on sleep and EEG spectra of the rat

Vigilance states and EEG power density of the rat were determined after a 3- or 6-h sleep deprivation (SD) in the beginning of the 12-h light period. In comparison to baseline, non-rapid eye movement (REM) sleep showed a delayed and transitory increase after 3 h SD, and an immediate and persistent increase after 6 h SD. REM sleep was not affected. In non-REM sleep, EEG power density in the low-frequency range (0.75-6.0 Hz) was markedly enhanced after 6 h SD, but not significantly increased after 3 h SD. In REM sleep EEG activity in the 5-6 Hz band was increased after 6 h SD. We conclude that in the early part of the light period, 3 h waking prolongs non-REM sleep, whereas 6 h waking also enhances non-REM sleep intensity.     

Positive Occipital Sharp Transients in the Human Sleep EEG

Abstract: The characteristics of positive occipital sharp transients (POSTs) in the human sleep EEG were studied, and their characteristics were compared with those of lambda waves appearing in the occipital EEG during the waking state. The following findings were obtained: 1) POSTs were observed in 57% of 189 subjects examined during sleep. The incidence of the subjects showing POSTs was highest in the group of subjects aged 21–30 years. 2) The incidence of the subjects showing POSTs tended to be high among the subjects with a high alpha wave index. 3) The wave form and topography of POSTs had striking similarities to those of lambda waves. 4) The frequency of POSTs was highest during the initial 30 minutes' period of NREM sleep after the sleep onset in both nocturnal and diurnal sleep. 5) The frequency and amplitude of POSTs were not modified by changing the background illumination in the recording room. 6) No significant relation was found between the frequency of POSTs and dream experience during NREM sleep.