Physiology of Normal Sleep: From Young to Old

Human sleep, defined on the basis of electroencephalogram (EEG), electromyogram(EMG) and electrooculogram (EOG), is divided into rapid eye movement (REM) sleepand four stages of non–rapid eye movement (NREM) sleep. Collective monitoring andrecording of physiological data during sleep is called polysomnography. Sleep whichnormally starts with a period of NREM alternates with REM, about 4-5 times, everynight. Sleep pattern changes with increasing age. Newborns sleep for about 14-16hours in a day of 24 hours. Although there is a wide variation among individuals, sleepof 7-8.5 hours is considered fully restorative in adults. Apart from restorative andrecovery function, energy conservation could be one of the functions of sleep. The roleof sleep in neurogenesis, memory consolidation and brain growth has been suggested.Though progress in medical science has vastly improved our understanding of sleepphysiology, we still do not know all the functions of sleep.Key words : electroencephalogram, electromyogram, electrooculogram,polysomnography, REM sleep, non–REM sleep, newborns, circadian rhythm, autoregulation,sleep functio

Investigating the Role of Phox2B-expressing Glutamatergic Parafacial Zone Neurons in Sleep Wake Control

Inhibitory GABAergic neurons in the parafacial zone (PZGABA) are essential for slow wave sleep (SWS). Since existing literature about the heterogenous population of PZ neurons is lacking, questions remain regarding the non-GABAergic sleep active PZ neurons. This study seeks to determine if glutamatergic PZ neurons expressing the transcription factor Phox2B (PZPhox2B) participate in sleep-wake control. Phox2B-IRES-Cre mice received injections of adeno-associated virus containing Cre-dependent diphtheria toxin subunit A (DTA) DNA into the PZ (PZPhox2B-DTA). Analysis of injection sites revealed transfection covering the PZ and the locus coeruleus, also known to express Phox2B. We recorded the sleep-wake cycle of PZPhox2B-DTA mice and compared them with control mice, analyzing their sleep-wake quantity, fragmentation, and power spectral distribution. We found total amounts and cortical power for wakefulness, SWS, and REM sleep of PZPhox2B-DTA mice were unaffected. There was fragmentation in wakefulness during the active period for PZPhox2B-DTA mice, seen as a significant reduction in the amount of time and number of episodes spent in the longest bout; however, wakefulness during the rest period was not significantly altered. No significant change was found in the bout numbers and amounts for SWS and REM sleep of PZPhox2B-DTA mice. I was unable to confirm targeted ablation of PZPhox2B-DTA neurons due to a lack of reliable antibody staining. Therefore, it remains possible that ablation of PZPhox2B neurons was incomplete and the wakeful fragmentation is due to neuronal ablation outside of the PZ, such as in the neighboring LC

The brain decade in debate: VII. Neurobiology of sleep and dreams

This article is a transcription of an electronic symposium held on February 5, 2001 by the Brazilian Society of Neuroscience and Behavior (SBNeC) during which eight specialists involved in clinical and experimental research on sleep and dreaming exposed their personal experience and theoretical points of view concerning these highly polemic subjects. Unlike most other bodily functions, sleep and dreaming cannot, so far, be defined in terms of definitive functions that play an ascribable role in maintaining the organism as a whole. Such difficulties appear quite clearly all along the discussions. In this symposium, concepts on sleep function range from a protective behavior to an essential function for maturation of the nervous system. Kleitman's hypothesis [Journal of Nervous and Mental Disease (1974), 159: 293-294] was discussed, according to which the basal state is not the wakeful state but sleep, from which we awake to eat, to protect ourselves, to procreate, etc. Dreams, on the other hand, were widely discussed, being considered either as an important step in consolidation of learning or simply the conscious identification of functional patterns derived from the configuration of released or revoked memorized information.Universidade de São Paulo Faculdade de Medicina Instituto de PsiquiatriaUniversity of Laval School of Medicine Department of PhysiologyRutgers State University Center for NeuroscienceUniversidade de São Paulo Instituto de Ciências Biomédicas Departamento de Fisiologia e BiofísicaUniversidade Federal de São Paulo (UNIFESP) Instituto do SonhoFacultad de Medicina de Montevideo Departamento de Fisiología NeurofisiologíaFlorida Atlantic University Center for Complex SystemsUniversidade de São Paulo Faculdade de Medicina Departamento de NeurologiaUNIFESP, Instituto do SonhoSciEL

Cortical Plasticity Induced by Transcranial Magnetic Stimulation during Wakefulness Affects Electroencephalogram Activity during Sleep

BACKGROUND:Sleep electroencephalogram (EEG) brain oscillations in the low-frequency range show local signs of homeostatic regulation after learning. Such increases and decreases of slow wave activity are limited to the cortical regions involved in specific task performance during wakefulness. Here, we test the hypothesis that reorganization of motor cortex produced by long-term potentiation (LTP) affects EEG activity of this brain area during subsequent sleep. METHODOLOGY/PRINCIPAL FINDINGS:By pairing median nerve stimulation with transcranial magnetic stimulation over the contralateral motor cortex, one can potentiate the motor output, which is presumed to reflect plasticity of the neural circuitry. This paired associative stimulation increases M1 cortical excitability at interstimulus intervals of 25 ms. We compared the scalp distribution of sleep EEG power following paired associative stimulation at 25 ms to that following a control paradigm with 50 ms intervals. It is shown that the experimental manipulation by paired associative stimulation at 25 ms induces a 48% increase in amplitude of motor evoked potentials. This LTP-like potentiation, induced during waking, affects delta and theta EEG power in both REM and non-REM sleep, measured during the following night. Slow-wave activity increases in some frontal and prefrontal derivations and decreases at sites neighboring and contralateral to the stimulated motor cortex. The magnitude of increased amplitudes of motor evoked potentials by the paired associative stimulation at 25 ms predicts enhancements of slow-wave activity in prefrontal regions. CONCLUSIONS/SIGNIFICANCE:An LTP-like paradigm, presumably inducing increased synaptic strength, leads to changes in local sleep regulation, as indexed by EEG slow-wave activity. Enhancement and depression of slow-wave activity are interpreted in terms of a simultaneous activation of both excitatory and inhibitory circuits consequent to the paired associative stimulation at 25 ms

On the relation between complex brain activity and consciousness

Why does it feel like something to be awake? I.e. how is consciousness generated by the body, the brain in particular? Seeking to map phenomenological properties of any first person experience to neural activity patterns, theories of consciousness suggest a correlation between a specific type of neural dynamical complexity and the level of consciousness: When awake and aware, all brain regions are to a certain extent connected and there is diversity in the interactions. In support of this, Casali et al. (2013) have used EEG and transcranial magnetic stimulation to show extensively that brain response activity to direct perturbation is the more diverse across regions and time, the higher the level of consciousness. The spatio-temporal diversity of the response signal is quantified by a single index, the perturbational complexity index (PCI), using a Lempel-Ziv compression algorithm. Motivated by this result, and given that spontaneous neural signals are easier to obtain than response signals to perturbation, this thesis proposes measures - based on Lempel-Ziv compression and entropy - to quantify spontaneous neural signal diversity across channels and observations. Our measures’ sensitivity and specificity to conscious level is demonstrated by re-analysing resting state scalp EEG during propofol-induced anaesthesia and depth electrode recordings during sleep stages, resulting in consistently higher scores for subjects that are awake than being in propofol-induced anaesthesia or non-rapid eye movement sleep. In addition we demonstrate that our measures score higher for states induced by psychedelic substances by re-analysing resting state magnetoencephalography (MEG) data. We further explore in computer simulation how our measures and PCI behave as a function of connectivity of coupled oscillators, informing models of brain mechanisms associated with the loss of consciousness. While our measures may be weaker than PCI in terms of specificity and sensitivity to conscious level, they are quick and easy to compute and applicable to readily available resting state data. This thesis provides strong evidence that cortical signal diversity is a hallmark of consciousness, as predicted by integrated information and complexity theories of consciousness. i

Effects of sleep deprivation on neural functioning: an integrative review

Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research