Regulation Of Slow Wave Sleep Research Articles

Somnambulism induced by Hydroxyzine

IntroductionSomnambulism or sleepwalking could be explained by dysfunction in the regulation of slow-wave sleep. It may be caused by drugs; in the literature, cases of somnambulism that occurred by olanzapine and lithium have been reported.ObjectivesDiscuss the association between somnambulism and Hydroxyzine.MethodsWe will discuss the case of a patient with bipolar disorder treated with olanzapine and lithium who experienced episodes of somnambulism after adding Hydroxyzine.ResultsA 42-year-old woman, with no history of somnambulism, followed in our department for a bipolar disorder type 1, treated with 750 mg of lithium and 20 mg of olanzapine. During her usual control, she reported insomnia Hydroxyzine was added at the dose of 50 mg. At the next medical appointment, she said that her husband had noticed that she waked up at night and she eats, she ambulates and searches things. Episodes that the patient did not remember. She was tranferd to the neurolgic departement. She did a neurological exam, an electroencephalogram, and a brain scan, witch were normal. The polysomnography confirmed the diagnosis. The neurologist retained the diagnosis of somnambulism induced by Hdroxizine regarding the chronology of the symptoms. The somnambulism ceased after stopping Hydroxyzine.ConclusionsLithium and olanzapine were associated with the occur of somnambulism, but hydroxyzine had never been reported as a somnambulism drug inducing. Drug interaction may explain this phenomenon.DisclosureNo significant relationships.

Astrocytic Ca2+ signaling is reduced during sleep and is involved in the regulation of slow wave sleep

Astrocytic Ca2+ signaling has been intensively studied in health and disease but has not been quantified during natural sleep. Here, we employ an activity-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake and naturally sleeping mice while monitoring neuronal Ca2+ activity, brain rhythms and behavior. We show that astrocytic Ca2+ signals exhibit distinct features across the sleep-wake cycle and are reduced during sleep compared to wakefulness. Moreover, an increase in astrocytic Ca2+ signaling precedes transitions from slow wave sleep to wakefulness, with a peak upon awakening exceeding the levels during whisking and locomotion. Finally, genetic ablation of an important astrocytic Ca2+ signaling pathway impairs slow wave sleep and results in an increased number of microarousals, abnormal brain rhythms, and an increased frequency of slow wave sleep state transitions and sleep spindles. Our findings demonstrate an essential role for astrocytic Ca2+ signaling in regulating slow wave sleep.

Remission of encephalopathy with status epilepticus (ESES) during sleep renormalizes regulation of slow wave sleep.

In previous studies, we showed an altered overnight decrease of non-rapid-eye-movement (NREM) sleep slow waves in children with encephalopathy related to status epilepticus during sleep (ESES). Here, we test the hypothesis that these alterations renormalize after remission of ESES. Because overnight decrease of slow waves has been linked to brain recovery and cognition, we investigate whether cognitive outcome is related to overnight changes of slow waves. We performed a retrospective analysis of longitudinal overnight electroencephalography (EEG) in 10 patients with idiopathic ESES. Automated slow wave detection and calculation of slope of slow waves during the first and last hour of NREM sleep were employed. Intraindividual comparisons were undertaken of the slope during active phase and after remission of ESES, and between patients after remission of ESES and healthy controls. Explorative analysis of the relationship between slow wave slope and cognitive outcome was performed. The slope of slow waves did not decrease significantly across the night during active ESES, particularly at the spike focus. After remission of ESES, the slope decreased significantly overnight. Compared to controls, there was no difference in overnight slope decrease. Association between slope and neuropsychological outcome showed best cognitive outcome after remission in those children (n = 3) who showed some degree of slope decline during active ESES. This study provides evidence that alterations of overnight changes of NREM-sleep slow waves during active ESES are reversible when ESES resolves, and that the severity of neuropsychological compromise might be related to the extent of slow wave impairment during ESES. Our findings suggest that analysis of slow waves might serve as a prognostic factor regarding cognitive outcome. ESES may serve as disease model of pathologic slow wave sleep and our results might be expanded to epilepsies with spike wave activation in slow wave sleep not only in children but also in adults.

A role for cortical nNOS/NK1 neurons in coupling homeostatic sleep drive to EEG slow wave activity

Although the neural circuitry underlying homeostatic sleep regulation is little understood, cortical neurons immunoreactive for neuronal nitric oxide synthase (nNOS) and the neurokinin-1 receptor (NK1) have been proposed to be involved in this physiological process. By systematically manipulating the durations of sleep deprivation and subsequent recovery sleep, we show that activation of cortical nNOS/NK1 neurons is directly related to non-rapid eye movement (NREM) sleep time, NREM bout duration, and EEG δ power during NREM sleep, an index of preexisting homeostatic sleep drive. Conversely, nNOS knockout mice show reduced NREM sleep time, shorter NREM bouts, and decreased power in the low δ range during NREM sleep, despite constitutively elevated sleep drive. Cortical NK1 neurons are still activated in response to sleep deprivation in these mice but, in the absence of nNOS, they are unable to up-regulate NREM δ power appropriately. These findings support the hypothesis that cortical nNOS/NK1 neurons translate homeostatic sleep drive into up-regulation of NREM δ power through an NO-dependent mechanism.

In response to “The effect of agomelatine on 5HT2C receptors in humans: a clinically relevant mechanism?” by Trevor Norman

We thank Dr. Norman for his interesting comments about the role of H1 receptors in the regulation of slow wave sleep. It is of course quite plausible that H1-receptor blockade could modify slow wave sleep (SWS) in humans; however, in a study with the selective H1 receptor antagonist, mepyramine, we saw no such effect (Solomon et al. 1989). Regardless of whether or not H1-receptors play a role in SWS regulation in humans, the key issue in the case of agomelatine is whether selective 5-HT2C receptor blockade is able by itself to increase SWS. In animals, there is good evidence that this is the case, and indeed, agomelatine, given in acute doses of 10 and 40 mg/kg, also increases SWS in rats, an effect mimicked by the selective 5-HT2C receptor antagonist, S32006 (Descamps et al. 2009). This suggests that a dose of agomelatine sufficient to block 5-HT2C receptors in humans should also increase SWS. However, we agree with Dr. Norman that to resolve the question of whether agomelatine does block 5-HT2C receptors in the human brain at clinically relevant doses, other models of 5-HT2C receptor activity will be needed.

Glutamate microinjection at the medial preoptic area enhances slow wave sleep in rats

A large body of evidence has established the role of the medial preoptic area (mPOA) in regulation of slow wave sleep (SWS). Although the mPOA neurons contain excitatory neurotransmitter glutamate, its role in sleep–wakefulness is not known. In the present study microinjection of monosodium glutamate (40, 80 and 120 ng) into the mPOA augmented SWS. Earlier reports have shown enhancement of paradoxical sleep by glutamate in other brain areas.

The effect of GABA A antagonist bicuculline on dorsal raphe nucleus and frontal cortex extracellular serotonin: A window on SWS and REM sleep modulation

We investigated the effects of the perfusion of γ-aminobutyric acid A antagonist bicuculline in the dorsal raphe nucleus, on brain 5-hydroxytryptamine level and on sleep. Perfusion of 25 and 50 μM bicuculline into the dorsal raphe nucleus dose-dependently increased dorsal raphe nucleus 5-hydroxytryptamine level during sleep and wakefulness. Frontal cortex 5-hydroxytryptamine level was not affected by either 25 or 50 μM perfusion. 25 μM bicuculline produced only minimal effects on sleep. 50 μM decreased rapid eye movement sleep, slow wave sleep 1 and 2 and increased waking. Sleep changes leveled out towards the end of the bicuculline perfusion despite serotonin levels were still elevated. This suggests that an adaptation mechanism may take place in order to counteract the high serotonergic output, producing uncoupling between serotonin level and behavioural state. The results support the notion that γ-aminobutyric acid is a strong modulator of dorsal raphe nucleus serotonergic neurons, and that this modulation is important in the regulation of slow wave sleep, rapid eye movement sleep and waking.

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.

Slow wave sleep in humans: Role of 5-HT 2A and 5-HT 2C receptors

We studied the effects of the 5-HT 2 receptor antagonists, ritanserin and ketanserin, on the sleep of healthy volunteers in order to clarify the role of 5-HT 2A and 5-HT 2C receptors in the regulation of slow wave sleep (SWS) in humans. Ritanserin, 5 mg, produced a substantially larger increase in SWS (51.4%) than either ketanserin, 20 mg (17.2%) or ketanserin, 40 mg (24.4%). Ritanserin has a significantly higher affinity than ketanserin for 5-HT 2C receptor binding sites in the human brain and, based on estimates of per cent occupancy by the two compounds at brain 5-HT 2A and 5-HT 2C receptors, we conclude that SWS in humans is primarily regulated by 5-HT 2C receptors.

Firing of neurons in the preoptic/anterior hypothalamic areas in rat: its possible involvement in slow wave sleep and paradoxical sleep

The basal forebrain including the preoptic area and anterior hypothalamus plays an important role in regulation of slow wave sleep. To examine whether this area is concerned also in a neural mechanism of paradoxical sleep, single neuronal activity in and around the preoptic area along with cortical EEG and neck EMG was recorded in undrugged, 12-h sleep-deprived rats whose head was fixed painlessly. The neurons whose activity was recorded during all states of sleep and wakefulness ( n = 98) were classified into following 5 groups according to their firing behavior in relation to sleep-waking states. (1) Neurons most active during paradoxical sleep ( n = 26). (2) Those most inactive during paradoxical sleep, some of which were inactive also during slow wave sleep ( n = 16). (3) Those specifically active during slow wave sleep ( n = 14). (4) Those less active during slow wave sleep than during wakefulness and paradoxical sleep ( n = 9). (5) Those whose activity showed no clear correlation with the sleep-waking states ( n = 33). About one third of neurons in each of groups (1) to (4) began to increase their sleep-related activity in advance of the shift of sleep/wakefulness state recognized in EEG. These results suggest that the preoptic and anterior hypothalamic areas are involved, at least in rats, in regulation of not only slow wave sleep but also paradoxical sleep.

The effects of fenfluramine on sleep and prolactin in depressed inpatients: A comparison of potential indices of brain serotonergic responsivity

The effects of fenfluramine, an indirect serotonergic agonist, on electroencephalographic sleep and prolactin secretion were assessed in 12 unmedicated inpatients with a primary diagnosis of major depressive episode. Compared to prefenfluramine profiles, sleep studies performed following fenfluramine administration showed a statistically significant reduction of slow-wave sleep (SWS) ( p < 0.001) and a corresponding increase in percentage of stage-2 sleep ( p < 0.007). Automated delta wave counts per min decreased significantly during the first nonrapid eye movement (NREM) period ( p = 0.04), and automated rapid-eye movement (REM) counts were also decreased in the second REM period ( p = 0.02). These effects on sleep electroencephalogram (EEG) did not correlate significantly with another measure of serotonergic responsivity, namely peak prolactin level following fenflurramine, nor with the severity of depression. The reductions in SWS and REM counts are proposed to be the result of time-dependent changes in serotonergic neurotransmission following the administration of fenfluramine. These findings are consistent with earlier work suggesting a role for serotonin in initiation and regulation of SWS and REM sleep.

Sleep and 5-HT 2 receptor sensitivity in recovered depressed patients

The increase in slow wave sleep which followed administration of the 5-HT 2 receptor antagonist, ritanserin, was not significantly different between a group of 12 recovered, drug free depressed patients and a group of 12 healthy matched controls. The results suggests that there is no underlying abnormality in the 5-HT 2 receptor regulation of slow wave sleep in recovered depressives, and that abnormalities in this measure reported previously in such patients may have been caused by use of concomitant tricyclic antidepressant medication. The baseline sleep parameters did not differ between recovered depressives and controls with the exception of stage 1 sleep, which was increased in the patient group.

Evidence for the Role of Serotonin in the Regulation of Slow Wave Sleep in Schizophrenia

Nocturnal sleep data and cerebrospinal fluid (CSF) concentrations of the biogenic amine metabolites were measured in 20 male schizophrenics. Consistent with other reports of a stage 4 sleep deficit in schizophrenia, measures of stage 4 sleep were low relative to normal reference data. Measures of stage 4 sleep in absolute amounts and corrected for total sleep were positively correlated with CSF concentrations of the serotonin metabolite, 5-hydroxyindole acetic acid (5-HIAA). CSF 5-HIAA was also correlated with measures of stage 3 sleep and total sleep time suggesting that serotonin may modulate the amount of slow wave sleep broadly defined and possibly sleep duration. Total stage 4 time was also correlated with the dopamine metabolite HVA; consequently, the specificity of the finding might be limited. Also, in this study, schizophrenia was used as a particular model for stage 4 deficits; however, the association of measures of stage 4 sleep with CSF levels of 5-HIAA is not thought to be specific to schizophrenia.

Sleep, gender, and depression: An analysis of gender effects on the electroencephalographic sleep of 302 depressed outpatients

Gender-related differences in electroencephalographic (EEG) sleep were examined in 151 pairs of men and women with major depression, all outpatients, matched for age and severity of depression. Across five decades (age 21–69), depressed men had less slow-wave sleep than did depressed women. Gender differences were small with respect to visually scored measures of slow-wave sleep time and percent, but moderate for gender differences in automated measures of slow-wave density. The time constant of the polygraph prramplifier significantly affected both visually scored and automatically scored slow-wave sleep. Other measures, such as REM sleep latency, first REM period duration, sleep efficiency, and early morning awakening, showed robust age effects, but no main effects for gender or gender-by-age interactions. Gender effects on slow-wave sleep and delta-wave counts in depression parallel gender effects seen in healthy aging. The possibility of occult alcohol use by depressed male outpatients cannot be definitely excluded as a partial explanation of the current findings. However, covarying for past alcohol abuse did not negate the statistical significance of the observed gender effects on slow-wave sleep and delta-wave density. The possibility of gender differences in slow-wave regulatory mechanisms is suggested, but similarity in temporal distribution of delta-wave density between the first and second non-rapid-eye-movement (NREM) periods does not support gender differences in slow-wave sleep regulation.

Slow wave sleep and 5-HT 2 receptor sensitivity during maintenance tricyclic antidepressant treatment

The 5-HT 2 receptor antagonist cyproheptadine significantly increased slow wavw sleep in 12 healthy control subjects but not in 12 patients with a history of major depression, maintained on tricyclic antidepressant treatment. Cyproheptadine produced a similar reduction in REM sleep in both groups of subjects. The results are consistent with the hypothesis that tricyclic antidepressant treatment alters brain 5-HT 2 receptor sensitivity, but a primary abnormality in slow wave sleep regulation in depressed patients cannot be excluded.

Effets de la section des nerfs optiques chez le babouin sur l'activité EEG et les cycles veille-sommeil

EEG rhythms recorded during the various states of alertness and sleep—waking cycles were studied in 4 baboons before and after optic nerve section. Visual deafferentation induced a general increase in amplitude of all the cortical rhythms, with general accentuation of pre-existing activities such as occipital eye movement potentials (EMPs), the fronto-rolandic rhythm and the alpha rhythm, spindles, REM ponto-geniculo-cortical (PGC) spikes; an increase in amplitude of the geniculate rhythmic activity, its frequency and occurrence was also noticed. When the blind baboons were placed in a monotonous environment, sleep—waking cycles occurred at any time of the 24 h. Total sleep time and total REM duration were not changed; however, deep sleep (stages 3 and 4) duration decreased (by around 50%) whereas stages 1 and 2 increased. The light factor thus plays a role in the sleep—waking cycle organization. However, its influence does not seem to be essential since its loss can be compensated by auditory stimulation. Finally, light possibly influences the systems involved in slow wave sleep regulation.

Effects of midbrain tegmental lesions on sleep and regional brain serotonin and norepinephrine levels in cats

A variety of experimental evidence has implicated the mesencephalic raphé complex of nuclei and the locus coeruleus in the regulation of slow-wave sleep and REM sleep, respectively, and in the maintenance of diencephalic and telencephalic levels of serotonin and norepinephrine. The present study defines further the critical loci subserving brain stem control of fore-brain monoamine levels and electrographic indicators of these two states of sleep. After baseline sleep profiles were determined, lesions were placed in the dorsal and ventral tegmentum of the medbrain in cats. Following these lesions, fluorometric assay of various brain regions revealed widespread depletion of serotonin and norepinephrine although few differences in the pattern of regional reduction of monoamines were noted between the cats with dorsal and ventral tegmental lesions. However, comparison of sleep-waking profiles of the animals taken 2 wk after the lesion with profiles taken before yielded no consistent alterations in waking, slow-wave sleep of REM sleep. These results indicate no clear-cut correlation between regional levels of brain amines and sleep-waking profiles.