Focal limbic sources create the large slow oscillations of the EEG in human deep sleep

BackgroundInitial observations with the human electroencephalogram (EEG) have interpreted slow oscillations (SOs) of the EEG during deep sleep (N3) as reflecting widespread surface-negative traveling waves that originate in frontal regions and propagate across the neocortex. However, mapping SOs with a high-density array shows the simultaneous appearance of posterior positive voltage fields in the EEG at the time of the frontal-negative fields, with the typical inversion point (apparent source) around the temporal lobe.MethodsOvernight 256-channel EEG recordings were gathered from 10 healthy young adults. Individual head conductivity models were created using each participant's own structural MRI. Source localization of SOs during N3 was then performed.ResultsElectrical source localization models confirmed that these large waves were created by focal discharges within the ventral limbic cortex, including medial temporal and caudal orbitofrontal cortex.ConclusionsAlthough the functional neurophysiology of deep sleep involves interactions between limbic and neocortical networks, the large EEG deflections of deep sleep are not created by distributed traveling waves in lateral neocortex but instead by relatively focal limbic discharges.     

Transcranial Slow Oscillation Stimulation During Sleep Enhances Memory Consolidation in Rats

BackgroundThe importance of slow-wave sleep (SWS), hallmarked by the occurrence of sleep slow oscillations (SO), for the consolidation of hippocampus-dependent memories has been shown in numerous studies. Previously, the application of transcranial direct current stimulation, oscillating at the frequency of endogenous slow oscillations, during SWS enhanced memory consolidation for a hippocampus dependent task in humans suggesting a causal role of slowly oscillating electric fields for sleep dependent memory consolidation.ObjectiveHere, we aimed to replicate and extend these findings to a rodent model.MethodsSlow oscillatory direct transcranial current stimulation (SO-tDCS) was applied over the frontal cortex of rats during non-rapid eye movement (NREM) sleep and its effects on memory consolidation in the one-trial object-place recognition task were examined. A retention interval of 24 h was used to investigate the effects of SO-tDCS on long-term memory.ResultsAnimals' preference for the displaced object was significantly greater than chance only when animals received SO-tDCS. EEG spectral power indicated a trend toward a transient enhancement of endogenous SO activity in the SO-tDCS condition.ConclusionsThese results support the hypothesis that slowly oscillating electric fields causal affect sleep dependent memory consolidation, and demonstrate that oscillatory tDCS can be a valuable tool to investigate the function of endogenous cortical network activity.     

Quantitative analysis of the effects of slow wave sleep deprivation during the first 3 h of sleep on subsequent EEG power density

Summary The relation between EEG power density during slow wave sleep (SWS) deprivation and power density during subsequent sleep was investigated. Nine young male adults slept in the laboratory for 3 consecutive nights. Sepctral analysis of the EEG on the 2nd (baseline) night revealed an exponential decline in mean EEG power density (0.25–15.0 Hz) over successive nonrapid eye movement — rapid eye movement sleep cycles. During the first 3 h of the 3rd night the subjects were deprived of SWS by means of acoustic stimuli, which did not induce wakefulness. During SWS deprivation an attenuation of EEG power densities was observed in the delta frequencies, as well as in the theta band. In the hours of sleep following SWS deprivation both the power densities in the frequency range from 1 to 7 Hz and the amount of SWS were enhanced, relative to the same period of the baseline night. Both the amount of EEG energy accumulating subsequent to SWS deprivation and its time course could be predicted accurately from the EEG energy deficit caused by SWS deprivation. The data show that the level of integral EEG power density during a certain period after sleep onset depends on the amount of EEG energy accumulated during the preceding sleep rather than on the time elapsed since sleep onset. In terms of the two-process model of sleep regulation (Borbély 1982; Daan et al. 1984) this finding indicates that EEG power density reflects the rate of decay of the regulating variable, S, rather than S itself, as was originally postulated.     

Antidepressant effects of selective slow wave sleep deprivation in major depression: a high-density EEG investigation

Sleep deprivation can acutely reverse depressive symptoms in some patients with major depression. Because abnormalities in slow wave sleep are one of the most consistent biological markers of depression, it is plausible that the antidepressant effects of sleep deprivation are due to the effects on slow wave homeostasis. This study tested the prediction that selectively reducing slow waves during sleep (slow wave deprivation; SWD), without disrupting total sleep time, will lead to an acute reduction in depressive symptomatology. As part of a multi-night, cross-over design study, participants with major depression (non-medicated; n = 17) underwent baseline, SWD, and recovery sleep sessions, and were recorded with high-density EEG (hdEEG). During SWD, acoustic stimuli were played to suppress subsequent slow waves, without waking up the participant. The effects of SWD on depressive symptoms were assessed with both self-rated and researcher-administered scales. Participants experienced a significant decrease in depressive symptoms according to both self-rated (p = .007) and researcher-administered (p = .010) scales, while vigilance was unaffected. The reduction in depressive symptoms correlated with the overnight dissipation of fronto-central slow wave activity (SWA) on baseline sleep, the rebound in right frontal all-night SWA on recovery sleep, and the amount of REM sleep on the SWD night. In addition to highlighting the benefits of hdEEG in detecting regional changes in brain activity, these findings suggest that SWD may help to better understand the pathophysiology of depression and may be a useful tool for the neuromodulatory reversal of depressive symptomatology.     

Small platform sleep deprivation selectively increases the average duration of rapid eye movement sleep episodes during sleep rebound

The single platform-on-water (flower pot) method is extensively used for depriving rapid eye movement sleep (REMS). Detailed comparison of sleep–wake architecture, recorded during the rebound period after spending three days on either a small or large platform, could separate the effects of REMS deficit from other stress factors caused by the procedure. A further aim of the study was to find the most characteristic REMS parameter of the rebound originating from REMS deficit. Rats were kept on a small or large platform for 72 h. Their fronto-parietal electroencephalogram, electromyogram and motility were recorded during the 24 h rebound at the beginning of the passive phase. A similar period of a home cage group was also recorded. The most typical differences between the two rebound groups were the increased cumulative time and longer average duration of REMS episodes without significant change in the number of these episodes of the small platform animals during the passive phase. Results obtained by cosinor analysis were in accordance with the findings above. Since we did not find any difference in the average duration of REMS episodes comparing the large platform rebound group and the home cage group, we concluded that the increased mean duration of REMS episodes is a selective marker for the rebound caused by small platform sleep deprivation, while other changes in sleep architecture may be the consequence of stress and also some sleep deficit.     

Effects of social stimuli on sleep in mice: non-rapid-eye-movement (NREM) sleep is promoted by aggressive interaction but not by sexual interaction

Sleep is generally considered to be a process of recovery from prior wakefulness. In addition to being affected by the duration of the waking period, sleep architecture and sleep EEG also depend on the quality of wakefulness. In the present experiment, we examined how sleep is affected by different social stimuli (social conflict and sexual interaction). Male C57BL/6J mice were placed in the cage of an aggressive dominant male or an estrous female for 1 h in the middle of the light phase. The conflict with an aggressive male had a pronounced NREM sleep-promoting effect. EEG slow wave activity, a measure of NREM sleep intensity, was increased for about 6 h and NREM sleep time was significantly increased for 12 h. REM sleep was strongly suppressed during the remainder of the light phase after the conflict, followed by a rebound later in the recovery phase. The sexual interaction, in contrast, had only mild effects. Both NREM sleep and REM sleep were somewhat suppressed shortly after the interaction. In a separate group of mice, blood samples were taken to measure prolactin and corticosterone. The results suggest that the temporary suppression of REM sleep following the social stimuli may be partly due to elevated corticosterone. The different effects of the social stimuli on NREM sleep are not easily explained by differences in the hormone responses. In conclusion, although both social conflict and sexual interaction induce a strong physiological activation, only social conflict has a strong stimulatory effect on NREM sleep mechanisms.     

Auditory arousal thresholds after selective slow-wave sleep deprivation.

OBJECTIVES: The aim of this study is to assess Auditory Arousal Thresholds (AATs) three times during an undisturbed baseline night and to compare them to AATs during the recovery night that follows two consecutive nights of selective SWS deprivation. The presence of a time-of-night effect on AATs will also be assessed. METHODS: Ten male Ss slept in the laboratory for 6 consecutive nights. The first two nights were undisturbed. The 3rd night was considered as baseline. During the 4th and 5th nights, selective SWS deprivation was obtained by means of acoustic stimulation. The 6th night was a recovery. In the last 4 nights Ss were awakened three times, after 2, 5 and 7.5 h of sleep, respectively. All the awakenings were carried out from stage 2 (after at least 5 consecutive min of stage 2), by means of 1000 Hz ascending tone series. The AAT determination was based on EEG-EMG criteria: at least 10-s of clear alpha rhythm and/or a 10 s movement arousal. RESULTS: During both deprivation nights, SWS amount was close to zero. In the ensuing recovery night a significant SWS rebound was found, accompanied by a significant increase of AATs with respect to the baseline. Furthermore, there was a significant linear decrease of AATs during the night. Finally, the individual correlations between AATs and SWS amount were significant in 4 out of 10 Ss. CONCLUSIONS: These results confirm that AATs are a reliable index of sleep depth by showing that the SWS rebound following selective SWS deprivation is paralleled by a significant AAT enhancement. The experimental paradigm also allows us to claim that AATs show a decreasing linear trend during the night, having excluded any procedural bias. Finally, AATs can be directly related to SWS amount that preceded the awakening, although the individual correlations between AATs and SWS have to be considered with caution, given the high inter-subject variability and the small number of observations.     

Delayed changes of sleep duration after rewarded olfactory discrimination learning in the rat

The aim of this experiment was to determine if a task of associative olfactory learning, based on the ethological repertory of rats and learnt rapidly in 5 successive trials, could modify slow wave sleep (SWS) and/or paradoxical sleep (PS) duration after learning and/or after a retrieval–reactivation test 24 h later. Somnopolygraphic recordings were performed for 20 h per day on trained and control (submitted to a pseudo-learning test) rats. SWS and PS durations were analyzed per 20 h and per 4 h time-periods. Compared to control rats, after learning, trained rats showed a significant increase in SWS duration counterbalanced by a significant decrease in wake duration focused on the 5–8 h post-training time-window and a significant decrease in PS duration during the 17–20 h post-training time-window. After the retrieval–reactivation test trained rats only showed a decreased PS duration compared to control rats submitted to a pseudo-retrieval test. Thus, a rather simple learning task succeeded in eliciting an increase in SWS duration in a limited time-window. As the learning task used can be compared to human associate-paired learning, this result sustains the hypothesis of a link between declarative memory and SWS. In control rats, changes in PS duration might be linked to odorized-environment exposure.     

Peripheral and central blockade of interleukin-6 trans-signaling differentially affects sleep architecture

The immune system is known to essentially contribute to the regulation of sleep. Whereas research in this regard focused on the pro-inflammatory cytokines interleukin-1 and tumor necrosis factor, the role of interleukin-6 (IL-6) in sleep regulation has been less intensely studied, probably due to the so far seemingly ambiguous results. Yet, this picture might simply reflect that the effects of IL-6 are conveyed via two different pathways (with possibly different actions), i.e., in addition to the ‘classical’ signaling pathway via the membrane bound IL-6 receptor (IL-6R), IL-6 stimulates cells through the alternative ‘trans-signaling’ pathway via the soluble IL-6R. Here, we concentrated on the contributions of the trans-signaling pathway to sleep regulation. To characterize this contribution, we compared the effect of blocking IL-6 trans-signaling (by the soluble gp130Fc fusion protein) in the brain versus body periphery. Thus, we compared sleep in transgenic mice expressing the soluble gp130Fc protein only in the brain (GFAP mice) or in the body periphery (PEPCK mice), and in wild type mice (WT) during a 24-h period of undisturbed conditions and during 18 h following a 6-h period of sleep deprivation. Compared with WT mice, PEPCK mice displayed less sleep, particularly during the late light phase, and this was accompanied by decreases in slow wave sleep (SWS) and rapid eye movement (REM) sleep. Following sleep deprivation PEPCK mice primarily recovered REM sleep rather than SWS. GFAP mice showed a slight decrease in REM sleep in combination with a profound and persistent increase in EEG theta activity. In conclusion, peripheral and central nervous IL-6 trans-signaling differentially influences brain activity. Peripheral IL-6 trans-signaling appears to more profoundly contribute to sleep regulation, mainly by supporting SWS.     

Effects of manipulating body temperature on sleep in postmenopausal women

Study objectivesA decline in sleep quality, slow wave sleep (SWS) and slow wave activity (SWA) are common in older adults. Prior studies have shown that manipulating body temperature during sleep can increase SWS/SWA. The aim of this study was to determine the effects of manipulation of body temperatures during sleep, using a high heat capacity mattress, on SWS/SWA and heart rate in post-menopausal women.MethodsTwenty-four healthy postmenopausal women between 40 and 75 years of age (mean age 62.4 ± 8.2 years, mean BMI 25.4 ± 3.5 kg/m²) were randomized in a single-blind, counterbalanced, cross-over manner to sleep on either a high heat capacity mattress (HHCM) or a low heat capacity mattress (LHCM) a week apart. Sleep was recorded using polysomnography during an 8-h sleep opportunity. Core and peripheral temperature were recorded using an ingestible capsule and thermochron respectively.ResultsIn comparison to the LHCM, sleep on HHCM exhibited a selective increase in SWS (average increase in Stage N3 of 9.6 min (2.1%), p = 0.04) and in slow oscillatory (SO) activity (0.5–1 Hz) in the first NREM/REM cycle (p = 0.04). In addition, the HHCM induced a greater reduction in core body temperature (p = 0.002). The reduction in core body temperature (first 180 min after lights out) from LHCM to HHCM was associated (r = 0.5, p = 0.012) with the increase in SO activity (SO cycle 1 and 2/cycle 3 and 4). Average heart rate was 1.6 beats/minute lower across the night on the HHCM compared to the LHCM (p = 0.001).ConclusionsThe results of this study indicate that manipulation of body temperature during sleep may be a useful approach to enhance SWS sleep in postmenopausal women.     

A comparative study of the diagnostic value of drug-induced sleep EEGs and sleep EEGs following sleep deprivation in patients with complex partial seizures

Summary The purpose of the study was to investigate whether the sleep EEG after sleep deprivation has a stronger provocative effect than the drug-induced sleep EEG. For this purpose a sleep EEG, induced by 2 mg/kg body weight of promazine hydrochloride, was recorded. On the following day a sleep EEG of the same patient was recorded after sleep deprivation of 24–26 h. If only patients whose wake EEGs were free from epileptic activity are considered, the rate of provocation was 58%. As epileptic activity could be recorded even in the sleep EEG without sleep deprivation in 45%, the advantage gained by recording a sleep EEG after sleep deprivation (52%) is only relatively small. The occurrence of epileptic activity was shown to be significantly more frequent amongst women and those who developed epilepsy at a younger age. For practical purposes it is recommended that for those patients whose wake EEGs are free from epileptic activity, a sleep EEG—possibly drug-induced—should be recorded. Only in instances where epileptic activity can not then be recorded should a wake EEG after sleep deprivation be carried out, and followed immediately, if necessary, by a sleep EEG.Supported by the Deutsche Forschungsgemeinschaft     

Impairment of visuospatial memory is associated with decreased slow wave sleep in schizophrenia

Cognitive impairments such as memory deficits and sleep disturbances are common clinical features of schizophrenia. Since sleep plays an important role in consolidation of memory, we hypothesize, that there is an interrelationship between distinct alterations in sleep and memory performance in schizophrenia. We studied 17 patients with schizophrenia on stable antipsychotic medication with amisulpride (age range 22–44 years; 7 women) and 17 healthy controls (matched for age, gender and educational level). Sleep was recorded and scored according to the standard criteria by Rechtschaffen and Kales. Immediately before polysomnography and the morning after we performed neuropsychological tasks including Rey–Osterrieth Complex Figure Test and a test for recall of spatial location for testing aspects of declarative memory and a mirror tracing skill for procedural memory. In comparison to healthy controls, the patients showed a significant increase in sleep onset latency and a significant decrease in sleep efficiency and amount of slow wave sleep (SWS). Furthermore, the patients' performance in recall of the Rey-figure and of spatial location the next morning was significantly impaired. These impairments in the tests for visuospatial memory were positively correlated with reduction in the amount of SWS and in sleep efficiency. These results point to a functional interrelationship between regulation of SWS and performance in visuospatial memory in schizophrenia. If these results of our pilot study hold true, they will allow the development of innovative treatment strategies for neuropsychological deficits in patients with schizophrenia.     

Effects of pre-bedtime blue-light exposure on ratio of deep sleep in healthy young men

This study aimed to investigate the effects of pre-bedtime blue-light exposure on ratio of deep sleep and sleep quality. In this study, 11 healthy young men were exposed to three conditions for 1 h before bedtime: 1) incandescent light, 2) blue-light, or 3) blue light-blocking glasses on. The following morning, subjective sleep quality was measured using the Oguri–Shirakawa–Azumi Sleep Inventory. Sleep time, ratio of sleep, ratio of deep sleep, and body movements during sleep were measured using a mat sleep-scan (sleep scan, SL- 504; TANITA Corp., Japan) and an ambulatory portable sleep study system (LS-140; Fukuda Denshi Co. Ltd., Japan). Ratio of deep sleep was significantly decreased in the blue-light exposure group compared to the groups with incandescent light and blue light-blocking glasses (p < 0.01), There were no differences noted in sleep time or body movements among the three groups. These results suggest that blue-light exposure to affects sleep quality by reducing the ratio of deep sleep.     

The diagnostic value of the short sleep EEG and other provocative methods following sleep deprivation

Summary One hundred and eighty-five EEGs recorded after deprivation of sleep for 24h were evaluated. Valuable diagnostic information was found in 59% of the EEG recordings; 24% of the EEGs contained seizure activity. The duration of the stages of sleep and the frequency of seizure activity, paroxysmal sharp wave groups and localizing findings were analyzed. The sleep stages A to C (based on the Loomis scale) were reached for about equal duration by an EEG recording of 30–40 min; sleep stage D was reached only shortly and stage E was not observed. Pathological EEG findings appeared for the most part in the sleep stages A and B. Localized findings were pronounced in stage C. No significant differences pertaining to the occurrence and form of EEG patterns were found between patient groups with primary generalized seizures, psychomotor seizures or those with unclarified disturbances of consciousness. The combination of the short sleep EEG following 24h of sleep deprivation with subsequent use of the additional provocative methods of hyperventilation, photostimulation and hydration, yielded, in all, new information in 50% of the patients. Each of these additional methods contributed nearly equally to this information.

---

Zusammenfassung Es wurden 185 EEGs nach 24h Schlafentzug ausgewertet. Hiervon enthielten 110 EEGs (59%) diagnostisch weiterführende Befunde. In 24% fand sich Krampfaktivität. Es wurden die Dauer der Schlafstadien, die Häufigkeit des Auftretens von Krampfaktivität, paroxysmalen Steilwellengruppen und Lokalbefunden analysiert. Die Schlaftiefen A bis C (nach Loomis) wurden während einer EEG-Ableitung von 30–40 min gleichmäßig lang, Stadium D nur kurz, Stadium E nicht erreicht. Pathologische EEG-Befunde traten überwiegend in den Schlafstadien A und B auf. Lokalbefunde fanden sich besonders im Stadium C. Zwischen den Patientengruppen mit primär generalisierten Anfällen, psychomotorischen Anfällen sowie Zuständen ungeklärter Bewußtseinsstörung fand sich kein signifikanter Unterschied hinsichtlich Auftreten und Ausprägung der EEG-Veränderungen. Die regelmäßig durchgeführte Hyperventilation und Fotostimulation und die Flüssigkeitsbelastung, die nur bei negativen Vorbefunden zusätzlich durchgeführt wurde, ergaben zusammen in 50% eine neue Information.

     

The experience-dependent increase in deep sleep activity is reduced in children with attention-deficit/hyperactivity disorder

Objective/BackgroundLearning of a visuomotor adaptation task during wakefulness leads to a local increase in slow–wave activity (SWA, EEG power between 1 and 4.5 Hz) during subsequent deep sleep. Here, we examined this relationship between learning and SWA in children with attention-deficit/hyperactivity disorder (ADHD).Patients/MethodsParticipants were 15 children with ADHD (9.7–14.8 y, one female) and 15 age-matched healthy controls (9.6–15.7 y, three female). After the completion of a visuomotor adaptation task in the evening, participants underwent an all-night high-density (HD, 128 electrodes) sleep-EEG measurement.ResultsHealthy control children showed the expected right-parietal increase in sleep SWA after visuomotor learning. Despite no difference in visuomotor learning, the local up-regulation during sleep was significantly reduced in ADHD patients compared to healthy controls.ConclusionsOur results indicate that the local, experience-dependent regulation of SWA is different in ADHD patients. Because the customarily observed heightened regulation in children was related to sensitive period maturation, ADHD patients may lack certain sensitive periods or show a developmental delay.     

Animal sleep: a review of sleep duration across phylogeny

Sleep duration and placement within the twenty-four hour day have been primary indices utilized in the examination of sleep function. It is of value, therefore, to evaluate these variables in a wide range of animal species. The present paper examines the literature concerning sleep duration in over 150 animal species, including invertebrates, fish, amphibians, reptiles, birds, and 14 orders of mammals. We first present annotations of almost 200 studies, including number of animals used, photoperiod employed, sleep duration per twenty-four hours and placement of sleep period within the nychthemeron. Both behavioral and electrographic studies are reviewed, as are laboratory and field studies. These data are subsequently presented in a table with representative literature citations for each species. Following the table, a brief discussion is presented concerning some methodological issues which may affect the measurement of sleep duration and some suggestions are made for future examination of sleep duration.     

Polysomnographically determined sleep and body mass index in patients with insomnia

We assessed associations between polysomnographically determined sleep, especially the amount of slow-wave sleep (SWS), and body mass index (BMI) in patients with insomnia. One hundred and forty-one insomniacs and 55 healthy volunteers completed overnight polysomnographic recordings, and we measured height and body weight. No significant correlations were obtained between total sleep time and BMI among insomniacs. Compared with normal volunteers, insomnia patients exhibited longer sleep latency and shorter total sleep duration. While the two groups had no significant differences in BMI, insomniacs presented with more N1 but less time spend in SWS and rapid eye movement sleep (REMS). Based on their SWS time, we divided insomnia patients into three groups: short (26.99±13.88), intermediate (59.24±8.12), and long (102.21±26.17) SWS groups. The short-SWS group had significantly greater BMI than the long-SWS group. Further analyses with multiple linear regression showed a significant negative correlation between the amount of SWS and BMI scores in insomniacs, whereas no such correlation was found in healthy volunteers after controlling for potential confounds (e.g., age, sex and AHI). Our study suggests that low amounts of SWS may be associated with higher BMI in patients with insomnia.     

Sharply contoured theta waves are the human correlate of ponto-geniculo-occipital waves in the primary visual cortex

Objective

Ponto-geniculo-occipital (PGO) waves occurring along the visual axis are one of the hallmarks of REM sleep in experimental animals. In humans, direct evidence is scarce. There is no systematic study of PGO waves in the primary visual cortex.

Ketogenic diet improves sleep quality in children with therapy-resistant epilepsy

Summary:  Purpose: The study purpose was to evaluate sleep structure during ketogenic diet (KD) treatment in children with therapy-resistant epilepsy and to correlate possible alterations with changes in clinical effects on seizure reduction, seizure severity, quality of life (QOL), and behavior.
Methods: Eighteen children were examined with ambulatory polysomnographic recordings initially and after 3 months of KD treatment. Eleven children continued with the KD and were also evaluated after 12 months. Sleep parameters were estimated. Seizure frequency was recorded in a diary and seizure severity in the National Health Seizure Severity Scale (NHS3). QOL was assessed with a visual analogue scale. Child behavior checklist and Ponsford and Kinsella's rating scale of attentional behavior were used.
Results: KD induced a significant decrease in total sleep (p = 0.05) and total night sleep (p = 0.006). Slow wave sleep was preserved, rapid eye movement (REM) sleep increased (p = 0.01), sleep stage 2 decreased (p = 0.004), and sleep stage 1 was unchanged. Eleven children continued with the KD and were also evaluated after 12 months. They showed a significant decrease in daytime sleep (p = 0.01) and a further increase in REM sleep (p = 0.06). Seizure frequency (p = 0.001, p = 0.003), seizure severity (p < 0.001, p = 0.005) and QOL (p < 0.001, p = 0.005) were significantly improved at 3 and 12 months. Attentional behavior was also improved, significantly so at 3 months (p = 0.003). There was a significant correlation between increased REM sleep and improvement in QOL (Spearman r = 0.6, p = 0.01) at 3 months.
Conclusion: KD decreases sleep and improves sleep quality in children with therapy-resistant epilepsy. The improvement in sleep quality, with increased REM sleep, seems to contribute to the improvement in QOL.