Alpha Reactivity to Complex Sounds Differs during REM Sleep and Wakefulness

We aimed at better understanding the brain mechanisms involved in the processing of alerting meaningful sounds during sleep, investigating alpha activity. During EEG acquisition, subjects were presented with a passive auditory oddball paradigm including rare complex sounds called Novels (the own first name - OWN, and an unfamiliar first name - OTHER) while they were watching a silent movie in the evening or sleeping at night. During the experimental night, the subjects’ quality of sleep was generally preserved. During wakefulness, the decrease in alpha power (8–12 Hz) induced by Novels was significantly larger for OWN than for OTHER at parietal electrodes, between 600 and 900 ms after stimulus onset. Conversely, during REM sleep, Novels induced an increase in alpha power (from 0 to 1200 ms at all electrodes), significantly larger for OWN than for OTHER at several parietal electrodes between 700 and 1200 ms after stimulus onset. These results show that complex sounds have a different effect on the alpha power during wakefulness (decrease) and during REM sleep (increase) and that OWN induce a specific effect in these two states. The increased alpha power induced by Novels during REM sleep may 1) correspond to a short and transient increase in arousal; in this case, our study provides an objective measure of the greater arousing power of OWN over OTHER, 2) indicate a cortical inhibition associated with sleep protection. These results suggest that alpha modulation could participate in the selection of stimuli to be further processed during sleep.     

Brain oscillatory activity during sleep shows unknown dysfunctions in early encephalopathy

Electroencephalographic recordings in cirrhotic patients without overt hepatic encephalopathy (HE) have mainly been performed during wakefulness. Our aim was to quantify their alterations in nocturnal sleep electroencephalogram (EEG). In 20 patients and 20 healthy volunteers, we recorded a nocturnal digital polysomnography. Different sleep parameters were measured. Besides, we performed quantitative analysis of EEG (qEEG) as follows: spectral power in the different sleep stages was calculated in the frequency bands low δ, δ, θ, α, and σ. Also, the mean dominant frequency and Sleep Indexes were obtained. In comparison with controls, the group of patients showed (1) different alterations in both the microstructure and the macrostructure of sleep; (2) an increase in, both, θ band power and the average mean dominant frequency during rapid eye movement (REM); (3) in all sleep stages, a decrease of sleep electroencephalogram spectral power in low δ band and an increase in δ band: and (4) in stages N3 and REM, significant increases in the minimum of mean dominant frequency and in the respective sleep indexes. Therefore, in cirrhotic patients without overt HE, and likely having minimal hepatic encephalopathy, we found different alterations in both the microstructure and the macrostructure of nocturnal sleep. Also, sleep qEEG showed a brain dysfunction in slow oscillatory mechanisms intrinsic of sleep stages, with an increase in the frequency of its maximal electroencephalogram synchronization, from low δ to δ band. These alterations may reflect the onset of encephalopathy; sleep qEEG may, thus, be an adequate tool for its brain functional evaluation and follow-up.     

Role of cholinergic mechanisms of the ventrolateral preoptico-anterior hypothalamic area in regulation of sleep and wakefulness states in pigeons

Maintenance of wakefulness is established to accomplish muscarinic (M-) cholinergic receptor activation in the ventrolateral preoptic area of the hypothalamus. The "muscarinic" wakefulness is characterized by enhancement of electroencephalogram (EEG) power spectra in the 0.75-12 Hz band and by increase in brain temperature. Activation of nicotinic (N-) cholinergic receptors of the area produces an increase in the duration of slow wave sleep, EEG power spectra reduction in the 0.75-7 Hz band, a decrease in brain temperature. And its hyperactivation leads to wakefulness, during its episodes the brain temperature decreases. During M- and N-cholinergic receptor blockade, the sleep-wakefulness and thermoregulation changes opposite to their activation were found. It is suggested that M- and N-cholinergic receptors of the ventrolateral preoptic area in pigeons participate in the sleep-wakefulness regulation and this effect is related to influence of this area on GABA-ergic system.     

Role of Homer proteins in the maintenance of sleep-wake states

Sleep is an evolutionarily conserved process that is linked to diurnal cycles and normal daytime wakefulness. Healthy sleep and wakefulness are integral to a healthy lifestyle; this occurs when an organism is able to maintain long bouts of both sleep and wake. Homer proteins, which function as adaptors for group 1 metabotropic glutamate receptors, have been implicated in genetic studies of sleep in both Drosophila and mouse. Drosophila express a single Homer gene product that is upregulated during sleep. By contrast, vertebrates express Homer as both constitutive and immediate early gene (H1a) forms, and H1a is up-regulated during wakefulness. Genetic deletion of Homer in Drosophila results in fragmented sleep and in failure to sustain long bouts of sleep, even under increased sleep drive. However, deletion of Homer1a in mouse results in failure to sustain long bouts of wakefulness. Further evidence for the role of Homer1a in the maintenance of wake comes from the CREB alpha delta mutant mouse, which displays a reduced wake phenotype similar to the Homer1a knockout and fails to up-regulate Homer1a upon sleep loss. Homer1a is a gene whose expression is induced by CREB. Sustained behaviors of the sleep/wake cycle are created by molecular pathways that are distinct from those for arousal or short bouts, and implicate an evolutionarily-conserved role for Homer in sustaining these behaviors.     

Dreaming and offline memory processing

The activities of the mind and brain never cease. Although many of our waking hours are spent processing sensory input and executing behavioral responses, moments of unoccupied rest free us to wander through thoughts of the past and future, create daydreams, and imagine fictitious scenarios. During sleep, when attention to sensory input is at a minimum, the mind continues to process information, using memory fragments to create the images, thoughts, and narratives that we commonly call 'dreaming'. Far from being a random or meaningless distraction, spontaneous cognition during states of sleep and resting wakefulness appears to serve important functions related to processing past memories and planning for the future. From single-cell recordings in rodents to behavioral studies in humans, recent studies in the neurosciences suggest a new conception of dreaming as part of a continuum of adaptive cognitive processing occurring across the full range of mind/brain states.     

Groups of passive and active control state in longitudinal experiments: an electrophysiological study

Long-term electrophysiological experiments were carried out with rats with chronically implanted electrodes into dopaminergic brain structures. Within 4 weeks after surgery, the relative spectral power of electrical activity in the delta1 and delta2 frequency bands decreased, while the relative spectral power in the alpha, beta1 and beta2 bands increased. A delayed (to the 4-5th week after surgery) increase in the total amount of sleep and REM sleep percent was observed in the sleep architecture of these animals. Multiple (during 2 weeks daily) intraperitoneal saline injections altered the dynamic of electrophysiological indices on the 2nd-3rd postsurgery weeks. The total sleep amount being not increased, the total and mean REM sleep durations increased, and the dynamic of the relative spectral power of electrical activity in the dopaminergic brain structures in the delta1, alpha and beta2 bands was found to be changed.     

Evolutionary aspects of interaction of sleep and stress: Phylo- and ontogenetic approach

This work considers comparative behavioral, somatoautonomic, and neurophysiological characteristics of three forms of passive defensive behavior included in the amphibian wakefulness-sleep cycle and their dynamics in the ascending vertebrate series. Considered in parallel is sleep formation in early postnatal ontogenesis of mature-and immature-born mammals-from undifferentiated sleep to the mature sleep divided into two phases as well as of stress-reaction. Comparative phylo-and ontogenetic analysis of several aspects of stress-reactions, sleep, and immobility phenomenon of the catalepsy type allows concluding that the immobility state of the catalepsy type in amphibians and reptiles can be considered the preadaptive behavior type that underlies the homoiothermal stress-reaction. It is the genetically programmed to the poikilothermal state characterized by a relatively high animal alertness, a freezing of the animal in the immobile, but active posture, with a possibility of a fast exit into the wakefulness state, which, alongside with other somatoautonomic and neurophysiological characteristics, which determines the entire subsequent complex of evolutionary morphofunctional changes of neuroregulatory and hormonal changes in the homoiothermal organism. In poikilothermal animals, this in many aspects unspecific behavioral adaptive reaction is realized at the corresponding hormonal and neurological levels of development of the organism and promotes fast mobilization and stabilization of constancy of the internal medium. At the higher evolutionary ladder levels, on the background of maturation of most neurotransmitter systems of brain and the hypothalamo-pituitary-adrenal system, the leading role in the stress-reaction regulation begins to be played predominantly by hormones, and only in the phase of the stress-reaction alertness, there are observed elements of activation of extrapyramidal systems of regulation of locomotor activity, which is manifested as the cataleptic freezing reaction. Thus, stress as the general adaptational syndrome reflects evolutionary regularities of development of specific functions supporting the total homeostasis. A scheme of evolutionary development of the wakefulness-sleep cycle in the vertebrate subtype is presented; according to it, the immobility state of the catalepsy type, on one hand, is considered as a part of wakefulness providing mainly specific elements of the stress-reaction, while, on the other hand,—as a certain step of the process of inhibition in CNS for subsequent involvement of the sleep-regulatory systems of compensation and maintenance of recovery reactions.     

Sleeping Dreams, Waking Hallucinations, and the Central Nervous System

Consciousness is now considered a primary function and activity of the brain itself. If so, consciousness is simply the brain's interpretation and integration of all the information made available to it at any given time. On the assumption that the brain is active across all states of being (wakefulness, REM sleep, and NREM sleep), this article proposes that dreaming and hallucinations represent variations on the same theme. Under usual circumstances during wakefulness, the brain ignores internally generated activity and attends to environmental sensory stimulation. During sleep, dreaming occurs because the brain attends to endogenously generated activity. In unusual settings, such as sleep-deprivation, sensory deprivation, or medication or drug ingestion, the brain attends to exogenous and endogenous activities simultaneously, resulting in hallucinations, or wakeful dreaming. This concept is supported by numerous neurologic conditions and syndromes that are associated with hallucinations.     

Correlation between oscillations in ventilation and frequency content of the electroencephalogram.

Periodicities of ventilation are common in elderly subjects during stage 1/2 sleep. The mechanism producing these periodicities is unknown. We hypothesized that the oscillations in ventilation might be related to oscillations in sleep state. To address this hypothesis, we examined, using cross correlation, the relationship between the oscillations in ventilation and parameters (alpha power, mean frequency) derived from spectral analysis of the electroencephalogram. In wakefulness, although ventilation and mean frequency, and ventilation and alpha power, were related, there were no consistent patterns to these relationships. Both positive and negative correlations were found. Clearer relationships were found in stage 1/2 sleep. Correlation between mean frequency and ventilation was the most consistent. All correlations were positive; i.e., ventilation fell as mean frequency fell. The maximum correlation occurred at zero lag between the time series. Thus these oscillations are synchronous within the time resolution of our methodology. These data are compatible with the hypothesis that the initiation of apnea in stage 1/2 sleep is related to a reduction in the state-dependent input to the ventilatory control system.     

Changes in electrical brain activity in patients with panic disorders

Brain electrical activity was recorded in 38 patients with typical and in 42 patients with atypical panic disorders, also in 30 normal controls. Compared to controls, patients both with typical and with atypical panic disorders differed significantly in reduced spectral power of the EEG alpha band in the right hemisphere. Moreover, in patients with typical panic disorders, the spectral power of the EEG beta1 band was increased in the frontal, temporal, central, and parietal areas of the right hemisphere. In patients with atypical panic disorders, the spectral power of the theta band was increased in the temporal areas of the right hemisphere. The changes in the EEG activity in patients with typical panic disorders are supposed to reflect an increase in activity of non-specific systems of the mesencephalic reticular formation, and the EEG changes in patients with atypical panic attacks may be associated with increased activity of the temporolimbic brain structures.     

Synchronized oscillations at alpha and theta frequencies in the lateral geniculate nucleus

In relaxed wakefulness, the EEG exhibits robust rhythms in the alpha band (8-13 Hz), which decelerate to theta (approximately 2-7 Hz) frequencies during early sleep. In animal models, these rhythms occur coherently with synchronized activity in the thalamus. However, the mechanisms of this thalamic activity are unknown. Here we show that, in slices of the lateral geniculate nucleus maintained in vitro, activation of the metabotropic glutamate receptor (mGluR) mGluR1a induces synchronized oscillations at alpha and theta frequencies that share similarities with thalamic alpha and theta rhythms recorded in vivo. These in vitro oscillations are driven by an unusual form of burst firing that is present in a subset of thalamocortical neurons and are synchronized by gap junctions. We propose that mGluR1a-induced oscillations are a potential mechanism whereby the thalamus promotes EEG alpha and theta rhythms in the intact brain.     

Context-dependent EEG spectral characteristics during performance of tasks

Spatial and frequency EEG characteristics of two groups of healthy adult subjects were examined in two series of experiments, which differed in conditions of the second cognitive task in a trial. The first task was the same in the two series: subjects had to evaluate size relationship between two closely spaced circles. The second task successively presented in trials of the first series consisted in the recognition of words/pseudowords, and in the second series, subjects had to localize a target letter in a matrix. It was assumed that the cognitive performance in the first series predominantly involved the ventral visual system, whereas during task performance in the second series, predominant involvement of the ventral and dorsal visual systems alternated. Multichannel EEG fragments recorded prior to the presentation of the task pairs were analyzed. Analysis of variance of the EEG spectral power revealed the generalized significant effect of the factor of the second task in the pair for delta band and lower beta subband, the power being higher in the first series. Factor brain hemisphere had a significant effect for the alpha band in the occipital area, the spectral power being lower in the left hemisphere for both experimental series. The task x hemisphere interaction was significant in the temporal cortical areas for the EEG power in alpha2 band, i.e., the predominant involvement of the ventral visual system was associated with stronger asymmetry of alpha2 rhythm and lower spectral power in this band in the left temporal area. Thus, the character of the forthcoming cognitive activity was shown to be reflected in spatio-frequency characteristics of the preceding EEG.     

Rhythms of slow-wave sleep and wakefulness in fluctuations of the potential of the oxidative-reductive status of the cerebral cortex

A method of recording slow ROSP's changes of the brain in chronic animals was used. It has been shown that wakefulness was accompanied by quasisinusoidal oscillations of ROSP (periods--several seconds). During slow sleep, oscillations of ROSP became more complicated and their periods were longer. It is suggested that transitions from sleep to wakefulness and vice versa are connected with removal of maximums of oxidative metabolism tension between biochemical systems characterized by different rhythms of self-regulation. Rhythmic oscillations of ROSP reveal the possibility of separate functional system of the ROSP of the brain cortex to synchronize their oscillations in the brain tissue (biochemical synergism).     

Spectral analysis of ventilation in elderly subjects awake and asleep

We studied the periodicities of ventilation in elderly subjects using digital comb filtering. Two groups of subjects were studied, those with and without sleep apnea. Measurements were made in wakefulness, stage 1-2 sleep, and where possible in stage 3-4 sleep. For each of the digital filters we calculated the average power of the oscillatory output. To compare subject groups we first specifically determined the average power in the filter with the maximum output. The mean of this measurement was greater in elderly subjects with apnea compared with those without apnea, both during wakefulness and stage 1-2 sleep. In both groups of subjects the cycle time of the major ventilatory oscillations was on the order of 40-60 s. There was no difference in this cycle time between the two groups of subjects in wakefulness or stage 1-2 sleep. Thus, whereas similar oscillatory processes occur in subjects with and without apnea, it is the magnitude of the oscillation that differs between the two groups. These conclusions are supported by analysis of the output of individual filters of the digital comb filter. In both groups, stage 1-2 sleep produced significantly increased oscillations in ventilation. Both in wakefulness and stage 1-2 sleep, significantly greater periodicities occurred in the apneic compared with the nonapneic group. In the few subjects who had sufficient data in stage 3-4 sleep for spectral analysis, ventilatory oscillations were virtually absent in this state. Our data suggest that subjects who develop apnea during sleep have an increased propensity for periodic breathing even while awake.     

Salubrinal, an inhibitor of protein synthesis, promotes deep slow wave sleep

Previous work showed that sleep is associated with increased brain protein synthesis and that arrest of protein synthesis facilitates sleep. Arrest of protein synthesis is induced during the endoplasmic reticulum (ER) stress response, through phosphorylation of eukaryotic initiation factor 2alpha (p-eIF2alpha). We tested a hypothesis that elevation of p-eIF2alpha would facilitate sleep. We studied the effects of intracerebroventricular infusion of salubrinal (Salub), which increases p-eIF2alpha by inhibiting its dephosphorylation. Salub increased deep slow wave sleep by 255%, while reducing active waking by 49%. Delta power within non-rapid eye movement (NREM) sleep was increased, while power in the sigma, beta, and gamma bands during NREM was reduced. We found that Salub increased expression of p-eIF2alpha in the basal forebrain (BF) area, a sleep-wake regulatory brain region. Therefore, we quantified the p-eIF2alpha-immunolabeled neurons in the BF area; Salub administration increased the number of p-eIF2alpha-expressing noncholinergic neurons in the caudal BF. In addition, Salub also increased the intensity of p-eIF2alpha expression in both cholinergic and noncholinergic neurons, but this was more widespread among the noncholinergic neurons. Our findings support a hypothesis that sleep is facilitated by signals associated with the ER stress response.     

Slow-wave sleep and molecular chaperones

Since long ago, one of the most vital issues mankind is concerned about is why spending almost one-third of human lives for sleep. This review addresses the major function of slow-wave sleep (SWS) and molecular mechanisms of its regulation. The main conclusions are presented below as the following generalizations and hypotheses. 1. SWS performs an energy-conserving function which developed parallel to the evolution of tachimetabolism and endothermy/homoiothermy. 2. Most significant reduction in the brain energy demands during deep SWS, characterized by increased EEG delta power, creates optimal conditions for the enhancement of anabolic processes and actualization of the major biological function of sleep—accelerating protein synthesis in the brain. 3. Conditions of paradoxical sleep (PS) as an “archeowakefulness”, containing the elements of endogenous stress, seem acceptable for chaperone expression required to fix misfolded proteins synthesized de novo during deep SWS. 4. Close integration of the HSP70 and HSP40 molecular systems, contained in the sleep center of the preoptic area of the hypothalamus, and their compensatory interrelationship contribute significantly to the maintenance of sleep homeostasis and implementation of its functions under non-stress conditions and during a long-term chaperone deficiency intrinsic to ageing and varied neuropathologies. 5. Cyclic changes in the protein synthesis rate (during deep SWS) and HSP70 chaperone expression (during wakefulness and, probably, PS), which occur on a daily basis throughout the entire lifetime, are critical for all vital functions of homeothermic organisms, including recovery of the nervous system structure and functions.     

Microinjection of glutamate into the pedunculopontine tegmentum induces REM sleep and wakefulness in the rat

The aim of this study was to test the hypothesis that the cells in the brain stem pedunculopontine tegmentum (PPT) are critically involved in the normal regulation of wakefulness and rapid eye movement (REM) sleep. To test this hypothesis, one of four different doses of the excitatory amino acid L-glutamate (15, 30, 60, and 90 ng) or saline (control vehicle) was microinjected unilaterally into the PPT while the effects on wakefulness and sleep were quantified in freely moving chronically instrumented rats. All microinjections were made during wakefulness and were followed by 6 h of polygraphic recording. Microinjection of 15- ng (0.08 nmol) and 30-ng (0.16 nmol) doses of L-glutamate into the PPT increased the total amount of REM sleep. Both doses of L-glutamate increased REM sleep at the expense of slow-wave sleep (SWS) but not wakefulness. Interestingly, the 60-ng (0.32 nmol) dose of L-glutamate increased both REM sleep and wakefulness. The total increase in REM sleep after the 60-ng dose of L-glutamate was significantly less than the increase from the 30-ng dose. The 90-ng (0.48 nmol) dose of L-glutamate kept animals awake for 2-3 h by eliminating both SWS and REM sleep. These results show that the L-glutamate microinjection into the PPT can increase wakefulness and/or REM sleep depending on the dosage. These findings support the hypothesis that excitation of the PPT cells is causal to the generation of wakefulness and REM sleep in the rat. In addition, the results of this study led to the identification of the PPT dosage of L-glutamate that optimally induces wakefulness and REM sleep. The knowledge of this optimal dose will be useful in future studies investigating the second messenger systems involved in the regulation of wakefulness and REM sleep.