REM Sleep Episodes Research Articles

Cortical activation in REM behavior disorder mimics voluntary movement. An electroencephalography study

ObjectivesMotor symptoms of Parkinson’s disease improve during REM sleep behavior disorder movement episodes. Our aim was to study cortical activity during these movement episodes, in patients with and without Parkinson’s disease, in order to investigate the cortical involvement in the generation of its electromyographic activity and its potential relationship with Parkinson’s disease. MethodsWe looked retrospectively in our polysomnography database for patients with REM sleep behavior disorder, analyzing fifteen patients in total, seven with idiopathic REM sleep behavior disorder and eight associated with Parkinson’s disease. We selected segments of REM sleep with the presence of movements (evidenced by electromyographic activation), and studied movement-related changes in cortical activity by averaging the electroencephalographic signal (premotor potential) and by means of time/frequency transforms. ResultsWe found a premotor potential and an energy decrease of alpha–beta oscillatory activity preceding the onset of electromyographic activity, together with an increase of gamma activity for the duration of the movement. All these changes were similarly present in REM sleep behavior disorder patients with and without Parkinson’s disease. ConclusionsMovement-related changes in electroencephalographic activity observed in REM sleep behavior disorder are similar to those observed during voluntary movements, regardless of the presence of Parkinson’s disease motor symptoms. SignificanceThese results suggest a main involvement of the cortex in the generation of the movements during REM sleep.

The Wave Model of Sleep Dynamics and an Invariant Relationship between NonREM and REM Sleep.

Explaining the complex structure and dynamics of sleep, which consist of alternating and physiologically distinct nonREM and REM sleep episodes, has posed a significant challenge. In this study, we demonstrate that a single-wave model concept captures the distinctly different overnight dynamics of the four primary sleep measures-the duration and intensity of nonREM and REM sleep episodes-with high quantitative precision for both regular and extended sleep. The model also accurately predicts how these polysomnographic measures respond to sleep deprivation or abundance. Furthermore, the model passes the ultimate test, as its prediction leads to a novel experimental finding-an invariant relationship between the duration of nonREM episodes and the intensity of REM episodes, the product of which remains constant over consecutive sleep cycles. These results suggest a functional unity between nonREM and REM sleep, establishing a comprehensive and quantitative framework for understanding normal sleep and sleep disorders.

Ultradian sleep cycles: Frequency, duration, and associations with individual and environmental factors—A retrospective study

ObjectiveSleep varies between individuals in response to sleep-wake history and various environmental factors, including light and noise. Here we report on the intranight variation of the ultradian nonrapid eye movement-rapid eye movement (NREM-REM) sleep cycle in 369 participants who have contributed to different laboratory studies from 1994 to 2020 at the Centre for Chronobiology, Basel, Switzerland. ResultsWe observed a large interindividual variability in sleep cycle duration, including NREM and REM sleep episodes in healthy participants who were given an 8-hour sleep opportunity at habitual bedtime in controlled laboratory settings. The median sleep cycle duration was 96 minutes out of 6064 polysomnographically-recorded cycles. The number and duration of cycles were not normally distributed, and the distribution became narrower for NREM sleep and wider for REM sleep later in the night. The first cycle was consistently shorter than subsequent cycles, and moderate presleep light or nocturnal noise exposure had no significant effects on ultradian sleep cycle duration. Age and sex significantly affected NREM and REM sleep duration, with older individuals having longer NREM and shorter REM sleep particularly in the end of the night, and females having longer NREM sleep episodes. High sleep pressure (ie, sleep deprivation) and low sleep pressure (ie, multiple naps) altered ultradian sleep cycles, with high sleep pressure leading to longer NREM sleep in the first cycle, and low sleep pressure leading to longer REM sleep episodes. Positive correlations were observed between N2 and NREM duration, and between N1 and REM duration. Weak intrasleep REM sleep homeostasis was also evident in our data set. ConclusionsWe conclude that ultradian sleep cycles are endogenous biological rhythms modulated by age, sex, and sleep homeostasis, but not directly responsive to (moderate levels of) environmental cues in healthy good sleepers.

Properties of REM sleep alterations with epilepsy.

It is usually assumed that individuals rest during sleep. However, coordinated neural activity that presumably requires high energy consumption is increased during REM sleep. Here, using freely moving male transgenic mice, the local brain environment and astrocyte activity during REM sleep were examined using the fibre photometry method with an optical fibre inserted deep into the lateral hypothalamus, a region that is linked with controlling sleep and metabolic state of the entire brain. Optical fluctuations of endogenous autofluorescence of the brain parenchyma or fluorescence of sensors for Ca2+ or pH expressed in astrocytes were examined. Using a newly devised method for analysis, changes in cytosolic Ca2+ and pH in astrocytes and changes in the local brain blood volume (BBV) were extracted. On REM sleep, astrocytic Ca2+ decreases, pH decreases (acidification) and BBV increases. Acidification was unexpected, as an increase in BBV would result in efficient carbon dioxide and/or lactate removal, which leads to alkalinization of the local brain environment. Acidification could be a result of increased glutamate transporter activity due to enhanced neuronal activity and/or aerobic metabolism in astrocytes. Notably, optical signal changes preceded the onset of the electrophysiological property signature of REM sleep by ∼20-30 s. This suggests that changes in the local brain environment have strong control over the state of neuronal cell activity. With repeated stimulation of the hippocampus, seizure response gradually develops through kindling. After a fully kindled state was obtained with multiple days of stimuli, the optical properties of REM sleep at the lateral hypothalamus were examined again. Although a negative deflection of the detected optical signal was observed during REM sleep after kindling, the estimated component changed. The decrease in Ca2+ and increase in BBV were minimal, and a large decrease in pH (acidification) emerged. This acidic shift may trigger an additional gliotransmitter release from astrocytes, which could lead to a state of hyperexcitable brain. As the properties of REM sleep change with the development of epilepsy, REM sleep analysis may serve as a biomarker of epileptogenesis severity. REM sleep analysis may also predict whether a specific REM sleep episode triggers post-sleep seizures.

Nitric Oxide Synthase Neurons in the Preoptic Hypothalamus Are NREM and REM Sleep-Active and Lower Body Temperature.

When mice are exposed to external warmth, nitric oxide synthase (NOS1) neurons in the median and medial preoptic (MnPO/MPO) hypothalamus induce sleep and concomitant body cooling. However, how these neurons regulate baseline sleep and body temperature is unknown. Using calcium photometry, we show that NOS1 neurons in MnPO/MPO are predominantly NREM and REM active, especially at the boundary of wake to NREM transitions, and in the later parts of REM bouts, with lower activity during wakefulness. In addition to releasing nitric oxide, NOS1 neurons in MnPO/MPO can release GABA, glutamate and peptides. We expressed tetanus-toxin light-chain in MnPO/MPO NOS1 cells to reduce vesicular release of transmitters. This induced changes in sleep structure: over 24 h, mice had less NREM sleep in their dark (active) phase, and more NREM sleep in their light (sleep) phase. REM sleep episodes in the dark phase were longer, and there were fewer REM transitions between other vigilance states. REM sleep had less theta power. Mice with synaptically blocked MnPO/MPO NOS1 neurons were also warmer than control mice at the dark-light transition (ZT0), as well as during the dark phase siesta (ZT16-20), where there is usually a body temperature dip. Also, at this siesta point of cooled body temperature, mice usually have more NREM, but mice with synaptically blocked MnPO/MPO NOS1 cells showed reduced NREM sleep at this time. Overall, MnPO/MPO NOS1 neurons promote both NREM and REM sleep and contribute to chronically lowering body temperature, particularly at transitions where the mice normally enter NREM sleep.

Sleep in the lesser mouse-deer (Tragulus kanchil).

The mouse-deer or chevrotains are the smallest of the ungulates and ruminants. They are characterized by a number of traits which are considered plesiomorphic for the Artiodactyla order. The objective of this study was to examine sleep in the lesser mouse-deer (Tragulus kanchil), which is the smallest in this group (body mass < 2.2 kg). Electroencephalogram, nuchal electromyogram, electrooculogram, and body acceleration were recorded in four adult mouse-deer females using a telemetry system in Bu Gia Map National Park in Vietnam. The mouse-deer spent on average 49.7 ± 3.0% of 24 h in non-rapid eye movement (NREM) sleep. REM sleep occupied 1.7 ± 0.3% of 24 h or 3.2 ± 0.5% of total sleep time. The average duration of REM sleep episodes was 2.0 ± 0.2 min, the average maximum was 5.1 ± 1.1 min, and the longest episodes lasted 8 min. NREM sleep occurred in sternal recumbency with the head held above the ground while 64.7 ± 6.4% of REM sleep occurred with the head resting on the ground. The eyes were open throughout most of the NREM sleep period. The mouse-deer displayed polyphasic sleep and crepuscular peaks in activity (04:00-06:00 and 18:00-19:00). The largest amounts of NREM occurred in the morning (06:00-09:00) and the smallest before dusk (at 04:00-06:00). REM sleep occurred throughout most of the daylight hours (08:00-16:00) and in the first half of the night (19:00-02:00). We suggest that the pattern and timing of sleep in the lesser mouse-deer is adapted to the survival of a small herbivorous animal, subject to predation, living in high environmental temperatures in the tropical forest undergrowth.

Motor Activity and "Neotenic" Sleep in the Naked Mole Rat (Heterocephalus glaber) under Isolation.

For the first time, continuous registration of motor activity and electroencephalogram for 40 days was carried out in four individuals of the naked mole rat (Heterocephalus glaber) in isolated conditions in the laboratory. A clear circadian rhythm of motor activity was found, with a gradual decrease during the night and an increase during the day, which remained both in the 12L/12D mode and in conditions of complete darkness. The rest states occupied, on average, about half the time of the day. There were both typical and atypical sleep periods, in which REM sleep episodes preceded NREM sleep periods. REM sleep percentage was unusually high (up to 50% of the total sleep time). During REM sleep episodes, a synchronized two-phase high-amplitude rhythm with a frequency of 12-16 Hz was recorded in the EEG. In addition, there were hard-to-identify periods of sleep, combining elements of both NREM and REM sleep. The sleep structure of naked mole rats resembles that of evolutionarily ancient species, as well as the "disorganized" sleep characteristic of the early stages of ontogenesis in altricial mammals.

Microinjection of melanin-concentrating hormone (MCH) into the median raphe nucleus promotes REM sleep in rats.

Melanin concentrating hormone (MCH) is a sleep-promoting neuromodulator synthesized by neurons located in the postero-lateral hypothalamus and incerto-hypothalamic area. MCHergic neurons have widespread projections including the serotonergic dorsal (DR) and median (MnR) raphe nuclei, both involved in the control of wakefulness and sleep. In the present study, we explored in rats the presence of the MCH receptor type 1 (MCHR-1) in serotonergic neurons of the MnR by double immunofluorescence. Additionally, we analyzed the effect on sleep of MCH microinjections into the MnR. We found that MCHR-1 protein was present in MnR serotonergic and non-serotonergic neurons. In this respect, the receptor was localized in the primary cilia of these neurons. Compared with saline, microinjections of MCH into the MnR induced a dose-related increase in REM sleep time, which was related to a rise in the number of REM sleep episodes, associated with a reduction in the time spent in W. No significant changes were observed in non-REM (NREM) sleep time. Our data strongly suggest that MCH projections towards the MnR, acting through the MCHR-1 located in the primary cilia, promote REM sleep.

Adaptation and survival: hypotheses about the neural mechanisms of unihemispheric sleep

ABSTRACT Sleep and wakefulness are opposite brain and body conditions that accomplish different but complementary functions. However, these opposing conditions have been combined in some animals by the adoption of a sleep/wake strategy that allows them to survive, while maintaining both an interaction with the environment at the same time as enabling brain and body recovery. They sleep with half of the brain while keeping the other half awake: a state known as unihemispheric sleep (US). Sleep of cetaceans is exclusively in the form of US; therefore, they experience neither bihemispheric sleep (BS) nor REM sleep. US episodes have also been recorded in eared seals and some species of birds. In those animals, US episodes are intermingled with episodes of BS and REM sleep. Studies have reported both a lateralized release of some neurotransmitters and a drop of brain temperature during US. The aims of this article are to formulate hypotheses about the neural mechanisms of unihemispheric sleep(US) based on findings regarding the neural mechanisms of the sleep/wake cycle of mammals. The neural mechanisms of the sleep/wake cycle are largely preserved across species, allowing to hypothesize about those triggering and regulating US.

Sleep Disturbances in Patients with Asperger Syndrome Related to the Severity of their Symptoms

Patients with Asperger syndrome (AS) usually report sleep problems. The objective of this study was to compare the general sleep structure of children with Asperger syndrome to that displayed by healthy children through polysomnographic study. Sleep characteristics were compared to severity of AS symptoms. Two groups of children aged 8–12 years were studied, one group with AS patients and the other with healthy children. Results show that patients with AS had a significant increase in sleep latency, REM latency and a decrease in the number of REM sleep episodes. It was also observed that the AS patients exhibit a correlation between the fragmentation of sleep and the increase in the intensity of the AS symptoms. It is concluded that sleep latency, REM latency and number of episodes are affected in AS patients and the AS symptoms are related to sleep disturbances in patients.

0012 REM Sleep in Ostrich Chicks

Abstract Introduction It was reported that adult ostriches displayed the longest REM sleep episodes (up to 5 min) and more REM sleep (24% of the nighttime) than any other avian species. In all mammals studied so far REM sleep predominates at early age suggesting it promotes development of the brain. The aim of this study was to examine REM sleep in ostrich chicks. Methods EEG, electrooculogram and electromyogram of the neck muscles were recorded in 4 chronically implanted 2–3 month old ostrich chicks over 3 nights. The last night was scored in 4-sec epochs for waking, nonREM and REM sleep. Results NonREM sleep and REM sleep in the ostrich chicks occurred when they were sitting or lying with the head held above the ground or rested on the ground. REM sleep was characterized by distinct rapid eye movements, head drops and eye closure. The amplitude of the EEG during episodes of REM sleep ranged between low voltage EEG, as recorded during quiet waking and high voltage slow waves, as recorded during nonREM sleep EEG. The ostrich chicks spent on average 70.7 + 2.2% of the nighttime in nonREM sleep and 12.3 + 3.9% in REM sleep. The episodes of REM sleep lasted on average 9 + 1 sec and ranged between 4 and 36 sec. Conclusion Similar to adult birds, 2–3 mo old ostrich chicks displayed a “mixed” sleep state which has features of both slow wave sleep / nonREM and REM sleep, as we have described in the platypus and echidna. An unexpected result of this study is the total amount and duration of episodes of REM were considerably smaller than has been reported in adult ostriches. More studies need to be done on the developmental and environmental determinants of REM sleep in the ostrich. Support The Russian Foundation for Basic Research (18-04-01252) and HL148574

0418 Effect of Acute Administration of DORA-12 on Sleep Impairment in the Aged PS19 Mouse Model of Tauopathy

Abstract Introduction Aged PS19 mice (MAPT P301S), a mouse model of tauopathy and neurodegeneration, display reduced NREM and REM sleep starting around 8-9 months before death around 12 months. Here, we tested the acute effect of a dual orexin receptor antagonist (DORA-12) on sleep in 11 mice (5 male, 6 female) at 10.3±1.8 months. Methods Two consecutive 24-hour recordings (12/12hr L:D cycle) were scored semi-automatically for non-REM sleep, REM sleep, and wake in mice implanted with EEG/EMG. Mice were treated with either vehicle (day 1) or 100mg/kg of DORA-12 (day 2) by oral gavage at both ZT0 and ZT9. Results After the first dose at ZT0, both latency to the first NREM sleep episode (paired t-test p=0.002) and to the first REM sleep episode (paired t-test p=0.005) was significantly shorter with DORA-12 (NREM: 20.8±17.8 min.; REM: 23.5±21.2 min.) compared to vehicle (NREM: 49.2±22.3 min.; REM: 127.0±93.3 min.). There was no difference in NREM or REM sleep latency observed after the second dose at ZT9. DORA-12 treatment increased NREM duration across the 24hr period (DORA-12: 664±52 min.; Veh: 601±54 min., paired t-test p=0.007) and also after the 2nd dose (DORA-12: 311±65 min.; Veh: 263±84 min., paired t-test p=0.009). DORA-12 treatment also increased REM duration across 24hrs (DORA-12: 61±30 min.; Veh: 48±29 min., paired t-test p=0.014) but not after the 2nd dose alone (DORA-12: 22±14 min.; Veh: 20±15 min., paired t-test p=0.388). Notably in both vehicle and DORA-12 conditions, we observed apparent dream enactment behavior including mastication, paw grasp, and fore limb extension during REM in 3 of 11 PS19 mice (all male), not typically observed in younger PS19 or age-matched non-transgenic mice, suggestive of a possible REM behavior disorder (RBD) phenotype. Wake-like behaviors occurred during theta-dominant EEG but with an EMG amplitude &amp;gt;4SD the preceding NREM sleep baseline for at least &amp;gt; 1sec. Conclusion In aged PS19 mice, DORA-12 was found to decrease the latency to NREM and REM after the first dose while also increasing NREM and REM duration across the entire 24hr recording period. We also capture a heretofore undescribed RBD-like phenotype in aged PS19 tauopathy mice. Support Merck MISP

0211 Sleep-Preparatory Behaviors Modulate Sleep Physiology in Mice

Abstract Introduction Prior to sleep, animals perform various sleep-preparatory behaviors, yet little is known about their contribution to sleep physiology. Sleep hygiene, which involves proper sleep preparation, is an effective treatment for insomnia in humans. The high prevalence of sleep disorders and drawbacks of available pharmacological interventions necessitate a better understanding of the ecological and evolutionary contexts of sleep. Nest-building is a sleep-preparatory behavior performed by many species. In this study, we aimed to determine whether the presence of a nest modulates sleep. Specifically, we investigated the effects of a nest on sleep/wake architecture and activity in wake-promoting neurons in mice. Methods To examine the role of nesting in sleep/wake architecture, we recorded EEG/EMG activity over 24 hrs (n=14, 7 males and 7 females) in the presence/absence of a nest. To determine whether the lack of a nest activates wake-promoting neurons, we utilized TRAP (targeted recombination in active populations) technology to label neurons activated by nest removal (n=4 mice per experimental group). Results Mice without nests exhibited increased latencies to NREM and REM sleep and spent less time asleep during the inactive/light phase. Mice without nests also exhibited shorter episodes of NREM and REM sleep and more transitions between arousal states. Additionally, our preliminary results suggest that nest removal significantly increases population activity in multiple brain regions, including several cortical and thalamic regions. Conclusion Our findings support the hypothesis that the presence of a nest facilitates and consolidates sleep. The causal role of specific neuronal populations in sleep fragmentation in the absence of a nest remains to be elucidated. Taken together, our findings provide the first evidence for a role of sleep-preparatory behaviors in the facilitation and consolidation of sleep and could shape the development of novel treatments for sleep disorders. Support This work is supported by the Sloan Alfred P. Foundation, the Brain and Behavior Research Foundation, and the Eisenberg Translational Research Award.

REM sleep-dependent short-term and long-term hourglass processes in the ultradian organization and recovery of REM sleep in the rat.

To evaluate the contribution of long-term and short-term REM sleep homeostatic processes to REM sleep recovery and the ultradian organization of the sleep wake cycle. Fifteen rats were sleep recorded under a 12:12 LD cycle. Animals were subjected during the rest phase to two protocols (2T2I or 2R2I) performed separately in non-consecutive experimental days. 2T2I consisted of 2 h of total sleep deprivation (TSD) followed immediately by 2 h of intermittent REM sleep deprivation (IRD). 2R2I consisted of 2 h of selective REM sleep deprivation (RSD) followed by 2 h of IRD. IRD was composed of four cycles of 20-min RSD intervals alternating with 10 min of sleep permission windows. REM sleep debt that accumulated during deprivation (9.0 and 10.8 min for RSD and TSD, respectively) was fully compensated regardless of cumulated NREM sleep or wakefulness during deprivation. Protocol 2T2I exhibited a delayed REM sleep rebound with respect to 2R2I due to a reduction of REM sleep transitions related to enhanced NREM sleep delta-EEG activity, without affecting REM sleep consolidation. Within IRD permission windows there was a transient and duration-dependent diminution of REM sleep transitions. REM sleep recovery in the rat seems to depend on a long-term hourglass process activated by REM sleep absence. Both REM sleep transition probability and REM sleep episode consolidation depend on the long-term REM sleep hourglass. REM sleep activates a short-term REM sleep refractory period that modulates the ultradian organization of sleep states.

Absent sleep EEG spindle activity in GluA1 (Gria1) knockout mice: relevance to neuropsychiatric disorders

Sleep EEG spindles have been implicated in attention, sensory processing, synaptic plasticity and memory consolidation. In humans, deficits in sleep spindles have been reported in a wide range of neurological and psychiatric disorders, including schizophrenia. Genome-wide association studies have suggested a link between schizophrenia and genes associated with synaptic plasticity, including the Gria1 gene which codes for the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. Gria1−/− mice exhibit a phenotype relevant for neuropsychiatric disorders, including reduced synaptic plasticity and, at the behavioural level, attentional deficits leading to aberrant salience. In this study we report a striking reduction of EEG power density including the spindle-frequency range (10–15 Hz) during sleep in Gria1−/− mice. The reduction of spindle-activity in Gria1−/− mice was accompanied by longer REM sleep episodes, increased EEG slow-wave activity in the occipital derivation during baseline sleep, and a reduced rate of decline of EEG slow wave activity (0.5–4 Hz) during NREM sleep after sleep deprivation. These data provide a novel link between glutamatergic dysfunction and sleep abnormalities in a schizophrenia-relevant mouse model.

Hippocampus and prefrontal cortex exhibit spindle-like waves during REM sleep

Objectives Spindles are considered as a major hallmark of non REM sleep (NREMS). These 10–16 Hz phasic oscillations are generated by thalamocortical loops. They are distributed in superficial and deep cortical structures, but also in the hippocampus, as observed in stereo-encephalographic (S-EEG) recordings in epileptic patients [1] , [2] . Our team recently found phasic oscillations in the sigma range (10–15 Hz) in the hippocampus and prefrontal cortex (PFC) during REM sleep (REMS) in rats. We aimed to probe the presence of this activity in the same areas in Human during REMS using S-EEG recordings. Methods Two-hundred and seventy-one drug-resistant epileptic patients explored in Lyon since 2007 with S-EEG recordings were retrospectively screened. Among them, 179 patients with leads in at least one hippocampus were selected. Recordings were visually analyzed to discard epileptic hippocampus. Finally, 12 patients with full night recordings were included. For each patient, 5 minutes of N2 and N3 were selected, as well as all REM sleep episodes. A Matlab script designed to detect and characterize spindle-like waves (SLW) was applied to the hippocampus, PFC and thalamus recordings. Results As expected, SLW were observed in the hippocampus, thalamus and PFC during NREMS. SLW were found in the hippocampus and PFC but not in the thalamus during REMS. SLW were less frequent in REMS than in NREMS. Their frequency was similar during both stages in the hippocampus (12.9 ± 0.5 Hz) but slightly faster during REM sleep than during NREM sleep in PFC (12.7 ± 0.5 vs 12.1 ± 0.5 Hz). REMS SLW and NREMS spindles density decreased with hippocampal spiking, suggesting that these activities are linked to physiological processes. Conclusion Our analysis revealed SLW in the hippocampus and PFC but not in the thalamus during REMS, suggesting that SLW results from different mechanisms than those involved in NREMS spindles generation.

Pinellia ternata (Thunb.) Makino Preparation promotes sleep by increasing REM sleep

Pinellia ternata (Thunb.) Makino Preparation (PTP) is widely used to treat insomnia in traditional Chinese medicine; however, its specific role is not clear. In this study, PTP was prepared at three concentrations. For locomotor activity tests, mice were treated with PTP and evaluated for 14 days. For polygraph recordings, mice were treated for 14 days and recorded after treatment. The main chemical constituents in PTP were identified by Ultra performance liquid chromatography/quadrupole time spectrometry (UPLC/Q-TOF-MS). The results showed that 0.9 g/mL PTP significantly reduced locomotor activity. The effect was related to the time of treatment. PTP reduced wakefulness and increased sleep in mice. Furthermore, PTP promoted sleep by increasing the number of REM sleep episodes with a duration of 64–128s and increasing the number of transitions from NREM sleep to REM sleep and from REM sleep to wakefulness. A total of 17 compounds were identified.

Characteristics of sleep structure in schoolchildren with high intellectual abilities

To study characteristics of sleep structure based on polysomnography (PSG) data of intellectually gifted schoolchildren. Forty-four 8-9 grade schoolchildren of the boarding school were examined. In the first stage, the level of intellectual development was assessed with Raven's Progressive Matrices. An analysis of medical history and clinical examination were performed as well. Based on the result of testing, the adolescents were divided into medium intelligence group (n=15) and high intelligence group (n=29). The second stage included PSG examination. There was a trend towards an increase in sleep latency with a significant decrease of deep sleep, a significant decrease in REM-sleep latency and an increase in the number of REM-sleep episodes in the high intelligence group. No significant differences in waking after sleep onset, number of arousals (EEG activations) and respiratory events, and oxygen saturation levels were identified. The characteristics of PSG in intellectually gifted schoolchildren should be considered as a compensatory and adaptive reaction in response to constant increased intellectual loads and stressful situations as risk factors for psychosomatic disorders.

The Sleep-Wake Cycle in the Nicotinic Alpha-9 Acetylcholine Receptor Subunit Knock-Out Mice.

There is a neural matrix controlling the sleep–wake cycle (SWC) embedded within high ranking integrative mechanisms in the central nervous system. Nicotinic alpha-9 acetylcholine receptor subunit (alpha-9 nAChR) participate in physiological processes occurring in sensory, endocrine and immune systems. There is a relationship between the SWC architecture, body homeostasis and sensory afferents so that disruption of afferent signaling is expected to affect the temporal organization of sleep and wake states. The analysis of the SWC of 9 nAChR knock-out animals may help to reveal the contribution of alpha-9 nAChR to sleep chronobiological determinants. Here we explore the polysomnogram in chronically implanted alpha-9 nAChR knock-out (KO) and wild-type (WT) individuals of the hybrid CBA/Sv129 mouse strain. Records were obtained in isolation chambers under a stable 12:12 light:dark cycle (LD). To unmask the 24-h modulation of the SWC a skeleton photoperiod (SP) protocol was performed. Under LD the daily quota (in %) of wakefulness (W), NREM sleep and REM sleep obtained in KO and WT animals were 45, 48 and 7, and 46, 46 and 8 respectively. Both groups exhibit nocturnal phase preference of W as well as diurnal and unimodal phase preference of NREM and REM sleep. The acrophase mean angles of KO vs. WT genotypes were not different (Zeitgeber Time: 6.5 vs. 14.9 for W, 4.3 vs. 2.8 for NREM sleep and 5.3 vs. 3.4 for REM sleep, respectively). Transference to SP do not affect daily state quotas, phase preferences and acrophases among genotypes. Unmasking phenomena of the SWC such as wake increment during the rest phase under SP was evident only among WT mice suggesting the involvement of retinal structures containing alpha-9 nAChR in masking processes. Furthermore, KO animals exhibit longer NREM and REM sleep episodes that is independent of illumination conditions. Consolidated diurnal NREM sleep contributed to obtain higher values of NREM sleep delta-EEG activity among KO mice during rest phase. In conclusion, circadian and sleep homeostatic aspects of the SWC are operative among alpha-9 nAChR KO animals. We propose that alpha-9 nAChR participate in retinal signaling processes responsible of the positive masking of sleep by light.

The spectrum of REM sleep-related episodes in children with type 1 narcolepsy.

Type 1 narcolepsy is a central hypersomnia due to the loss of hypocretin-producing neurons and characterized by cataplexy, excessive daytime sleepiness, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. In children, close to the disease onset, type 1 narcolepsy has peculiar clinical features with severe cataplexy and a complex admixture of movement disorders occurring while awake. Motor dyscontrol during sleep has never been systematically investigated. Suspecting that abnormal motor control might affect also sleep, we systematically analysed motor events recorded by means of video polysomnography in 40 children with type 1 narcolepsy (20 females; mean age 11.8 ± 2.6 years) and compared these data with those recorded in 22 age- and sex-matched healthy controls. Motor events were classified as elementary movements, if brief and non-purposeful and complex behaviours, if simulating purposeful behaviours. Complex behaviours occurring during REM sleep were further classified as 'classically-defined' and 'pantomime-like' REM sleep behaviour disorder episodes, based on their duration and on their pattern (i.e. brief and vivid-energetic in the first case, longer and with subcontinuous gesturing mimicking daily life activity in the second case). Elementary movements emerging either from non-REM or REM sleep were present in both groups, even if those emerging from REM sleep were more numerous in the group of patients. Conversely, complex behaviours could be detected only in children with type 1 narcolepsy and were observed in 13 patients, with six having 'classically-defined' REM sleep behaviour disorder episodes and seven having 'pantomime-like' REM sleep behaviour disorder episodes. Complex behaviours during REM sleep tended to recur in a stereotyped fashion for several times during the night, up to be almost continuous. Patients displaying a more severe motor dyscontrol during REM sleep had also more severe motor disorder during daytime (i.e. status cataplecticus) and more complaints of disrupted nocturnal sleep and of excessive daytime sleepiness. The neurophysiological hallmark of this severe motor dyscontrol during REM sleep was a decreased atonia index. The present study reports for the first time the occurrence of a severe and peculiar motor disorder during REM sleep in paediatric type 1 narcolepsy and confirms the presence of a severe motor dyscontrol in these patients, emerging not only from wakefulness (i.e. status cataplecticus), but also from sleep (i.e. complex behaviours during REM sleep). This is probably related to the acute imbalance of the hypocretinergic system, which physiologically acts by promoting movements during wakefulness and suppressing them during sleep.