EEG Delta Wave Research Articles

Integrated Biosignal Analysis to Provide Biomarkers for Recognizing Time Perception Difficulties.

Time perception refers to the capability to recognize the passage of time. The cerebellum is located at the back of the brain, underlying the occipital and temporal lobes. Dyschronometria is a cerebellar dysfunction, in which a person cannot precisely estimate the amount of time that has passed. Cardiac indicators such as heart rate (HR) variability have been associated with mental function in healthy individuals. Moreover, time perception has been previously studied concerning cardiac signs. Human time perception is influenced by various factors such as attention and drowsiness. An electroencephalogram (EEG) is a suitable modality for evaluating cortical reactions due to its affordability and usefulness. Because EEG has a high sequential outcome, it offers valuable data to explore variability in psychological situations. An electrocardiogram (ECG) records electrical signals from the heart to examine various heart conditions. The electromyography (EMG) technique detects electrical impulses produced by muscles. EEG, ECG, and EMG are integrated during time perception. This study evaluated the human body's time perception through the neurological, cardiovascular, and muscular systems using a simple neurofeedback exercise after time perception tasks. The three biosignals which are EEG, ECG, and EMG were investigated to use them as biomarkers for recognizing time perception difficulty as the main goal of the study. Five healthy college students with no health issues participated, and their EEG, ECG, and EMG were recorded while relaxing and performing a time wall estimation task and neurofeedback training. Previous research has shown the relationship between EEG frequency bands and the frontal center during time perception. Investigating the connection between ECG, EEG, and EMG under time perception conditions is significant. The results show that ECG (HR), EEG (Delta wave), and EMG (root mean square) are critical features in time perception difficulties. The ability and outcomes of multiple biomarkers might allow for improved diagnosis and monitoring of the progress of any treatment applications such as biofeedback training. Furthermore, those biomarkers could be used as useful for evaluating and treating dyschronometria.

Tripping on the edge of consciousness.

Herein the major accomplishments, trials and tribulations, and epiphanies experienced by James M. Krueger over the course of his career in sleep research are presented. They include the characterization of a) the supranormal EEG delta waves occurring during NREMS post sleep loss, b) Factor S as a muramyl peptide, c) the physiological roles of cytokines in sleep regulation, d) multiple other sleep regulatory substances, e) the dramatic changes in sleep over the course of infectious diseases, and f) sleep initiation within small neuronal/glial networks. The theory that the preservation of brain plasticity is the primordial sleep function is briefly discussed. These accomplishments resulted from collaborations with many outstanding scientists including James M. Krueger's mentors (John Pappenheimer and Manfred Karnovsky) and collaborators later in life, including Charles Dinarello, Louis Chedid, Mark Opp, Ferenc Obal jr., Dave Rector, Ping Taishi, Linda Toth, Jeannine Majde, Levente Kapas, Eva Szentirmai, Jidong Fang, Chris Davis, Sandip Roy, Tetsuya Kushikata, Fabio Garcia-Garcia, Ilia Karatsoreos, Mark Zielinski, and Alok De, plus many students, e.g. Jeremy Alt, Kathryn Jewett, Erika English, and Victor Leyva-Grado.

Correlations between cerebrospinal fluid biomarkers, neurocognitive tests, and resting-state electroencephalography (rsEEG) in patients with HIV-associated neurocognitive disorders

HIV-associated neurocognitive disorders (HAND) are highly prevalent in people living with HIV (PLWH) despite successful treatment with combination antiretroviral therapy (cART). HAND pathogenesis is complex and definitive surrogate biomarkers are not clearly defined. Brain function has been assessed through the evaluation of cortical source rhythms with delta waves associated with neurological impairment. The aim of this study was to assess the correlation between EEG cortical sources, cerebrospinal fluid (CSF) biomarkers, and neurocognitive tests in PLWH with HAND. PLWH with HAND without significant comorbidities were enrolled. Baseline rsEEG-LORETA waves, CSF biomarkers (t-tau, p-tau, β-amiloid42, neopterin, S100β), and neurocognitive tests were correlated and compared through non-parametric tests (Spearman's rho and Mann-Whitney); data are presented as medians (interquartile ranges). Fifty-four patients were enrolled. Median time of suppressed HIV-RNA and CD4+ T-lymphocyte were 10years (5.5-15) and 691/uL (477-929). Thirty-nine participants (72%) underwent CSF collection: abnormal biomarkers were found in a small percentage. Only neopterin showed a statistically significant correlation with delta activity [parietal (rho 0.579; p < 0.001), occipital (rho 0.493; p = 0.007), and global sources (rho 0.464 p = 0.011)]. Seven patients (12.9%) showed an abnormal neopterin level (> 1.5ng/mL) with significantly higher delta source activity compared to the ones with in-range concentrations. We observed a statistically significant correlation between working memory test Trail Making B with both CSF neopterin levels and delta waves (p values < 0.05). In a small sample of PLWH with HAND, we observed that higher CSF neopterin levels were associated with higher EEG delta waves and worse working memory tests.

The changes in electroencephalogram parameters in patients in the somatogenic phase of acute poisoning with opioid receptor agonists

To evaluate the parameters of the electroencephalogram (EEG) using the methods of computer processing of EEG data for an approach to the analysis of possible neurophysiological mechanisms underlying the fluctuations detected in the EEG in patients in the somatogenic phase of acute poisoning with opioid receptor agonists. Thirty-one patients were examined in the somatogenic phase of acute poisoning with opioid receptor agonists with a wakefulness level 3 to 15 points on the Glasgow Coma Scale. The EEG was recorded in accordance with the recommendations of the International Federation of Clinical Neurophysiology. The indicators of electrical activity of the brain were analyzed; computer processing of EEG data, including spectral analysis, localization of equivalent dipole sources of pathological electrical activity of the brain localization of the maximum of the equivalent density of EEG oscillation currents in the neocortex, was performed. Delta-band oscillations dominated in the majority of patients (65%, 20 patients). EEG delta waves were localized mainly at the level of the thalamus; using the method of low-resolution electromagnetic tomography, the localization of the maximum of the equivalent current density of delta oscillations in the projection of the neocortex was noted. Possible neurophysiological mechanisms of «pathological» delta waves recorded in the EEG of these patients are discussed. The changes on the EEG in these patients arise as a result of a disturbance of the function of the generator mechanisms of both cortical and activating structures of the brain, while the recorded slow-wave, mainly delta activity, taking into account the recording time (somatogenic phase), may be due to the action of secondary alternating factors (hypoxia and cerebral edema).

Relaxation Effects of Essential Oils Are Explained by Their Interactions with Human Brain Neurotransmitter Receptors and Electroencephalography Rhythms.

Inhaled essential oils (EOs) are bioavailable to the brain and are consistently reported to promote relaxation effects. Their mechanisms of action are however not well understood. The aim of this investigation was to assess the neuroactivity of EOs based on their (i) binding interactions to neurotransmitter receptors and (ii) bioelectrical activities in the brain as measured by electroencephalography (EEG). These EO properties were compared to those of reference pharmaceutical compounds with effects also measured by EEG. Relative receptor binding efficacies of 10 reference compounds, 180 EOs, and 9 EO extracts with 7 different neurotransmitter receptors were calculated using in silico molecular docking procedures. Changes in brain EEG rhythms, as standardized changes in absolute power, were determined for the reference compounds and selected EOs and compared to receptor binding efficacy results. The reference compounds had diverse receptor binding patterns, with EEG responses dominated by EEG-delta wave frequencies. In contrast, the receptor binding pattern of the EOs was remarkably consistent and replicated a subclinical affinity pattern corresponding to the inhibitory glycine-α-GLRA3 and dopamine-D2 receptors, producing responses dominated by EEG-alpha wave frequencies. The results support the hypothesis that EOs stimulate neuroactivity by modulating patterns of neurotransmission affecting alpha wave EEG responses.

Circadian differences in emergence from volatile anaesthesia in mice: involvement of the locus coeruleus noradrenergic system

BackgroundCircadian differences in the induction, maintenance, or emergence from volatile anaesthesia have not been well studied. MethodsThe minimal alveolar concentration (MAC) for preventing movement in response to a painful stimulus, MAC for loss of righting reflex (MACLORR), and MAC for recovery of righting reflex (MACRORR) in C57BL/6J male mice with isoflurane or sevoflurane exposure were measured during either the light or dark phase. Time to onset of loss of righting reflex (TimeLORR) and recovery of righting reflex (TimeRORR) upon exposure to 1 MAC of isoflurane or sevoflurane were determined. EEG was also monitored in the light and dark phase under isoflurane or sevoflurane exposure. The noradrenergic toxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was used to deplete noradrenergic neurones in the locus coeruleus to explore the impact of norepinephrine on these measurements. ResultsMACLORR, TimeLORR, and MAC did not show light- or dark-phase-dependent variations for either isoflurane or sevoflurane exposure. However, MACRORR was higher and TimeRORR was shorter in the dark phase than in the light phase for both isoflurane and sevoflurane exposure. The EEG delta wave power was higher but theta wave power was lower in the light phase than that in the dark phase during the rest state and emergence of anaesthesia. These light- and dark-phase-dependent changes in emergence were abolished in DSP-4-treated mice. ConclusionOur data show that circadian differences exist during emergence but not during induction or maintenance of sevoflurane or isoflurane anaesthesia. The locus coeruleus noradrenergic system may contribute to these differences.

Investigation of the effect of radiofrequency-electromagnetic field (RF-EMF) composed of mobile phone on brain EEG delta rhythms

Aim: The widespread use of mobile phones causes concern. The purpose of the study was to evaluate the effect of talking on the mobile phone for a short time on the brain EEG delta wave.Material and Methods: A total of twenty healthy medical students were included in the study. Bipolar EEG recordings of experimental and control groups were obtained in the study. For EEG delta wave, domain measurements, fast fourier transform (FFT) and power spectral density (PSD) analyzes were evaluated with the SPSS program.Results: As a result of the study, the values of the mean delta wave of all variables (value, FFT max, FFT max F, PSD Max F and PSD Max Power) were given between those using and not using mobile phones. There was a significant change in the EEG delta value (p0.05).Conclusion: Short-term cell phone exposures did not cause any significant change in frequency and power spectral densities, which may cause changes in delta value. However, long-term effects should be examined and studies are needed to monitor possible changes of the EEG recording during the phone call.

Interleukin-1 receptor accessory proteins are required for normal homeostatic responses to sleep deprivation.

Interleukin-1β (IL1) is a sleep regulatory substance. The IL1/IL1 type 1 receptor complex requires a receptor accessory protein (AcP) to signal. There are three isoforms of AcP. In the current experiments, mice lacking a neuron-specific isoform, called AcPb knockout (AcPb KO), or mice lacking AcP + AcPb isoforms (AcP KO) or wild-type (WT) mice were used. Spontaneous sleep and sleep responses to sleep deprivation (SD) between zeitgeber time (ZT) 20-ZT4 and ZT8-ZT16 were characterized. Furthermore, somatosensory cortical protein extracts were examined for phosphorylated (p) proto-oncogene tyrosine-protein kinase sarcoma (Src) and p38MAPK levels at ZT4 and ZT16 and after SD. Spontaneous sleep was similar in the three strains, except rapid eye movement sleep (REMS) duration between ZT12-ZT16 was greater in AcP KO than WT mice. After SD at ZT4, only WT mice had non-REMS (NREMS) rebounds. All mouse strains lacked an NREMS rebound after SD at ZT16. All strains after both SD periods had REMS rebounds. AcPb KO mice, but not AcP KO mice, had greater EEG delta wave (0.5-4 Hz) power during NREMS than WT mice. p-Src was very low at ZT16 but high at ZT4, whereas p-p38MAPK was low at ZT4 and high at ZT16. p-p38MAPK levels were not sensitive to SD. In contrast, p-Src levels were less after SD at the P = 0.08 level of significance in the strains lacking AcPb. We conclude that AcPb is required for NREMS responses to sleep loss, but not for SD-induced EEG delta wave or REMS responses.NEW & NOTEWORTHY Interleukin-1β (IL1), a well-characterized sleep regulatory substance, requires an IL1 receptor accessory protein (AcP); one of its isoforms is neuron-specific (called AcPb). We showed that in mice, AcPb is required for nonrapid eye movement sleep responses following 8 h of sleep loss ending 4 h after daybreak but did not affect rapid eye movement sleep rebound. Sleep loss reduced phosphorylation of proto-oncogene tyrosine-protein kinase sarcoma but not of the less sensitive p38MAPK, downstream IL1 signaling molecules.

Long term impairment of cognitive functions and alterations of NMDAR subunits after continuous microwave exposure

ObjectiveThe long term effects of continuous microwave exposure cannot be ignored for the simulation of the real environment and increasing concerns about the negative cognitive effects of microwave exposure. MethodsIn this study, 220 male Wistar rats were exposed by a 2.856GHz radiation source with the average power density of 0, 2.5, 5 and 10mW/cm2 for 6min/day, 5days/week and up to 6weeks. The MWM task, the EEG analysis, the hippocampus structure observation and the western blot were applied until the 12months after microwave exposure to detect the spatial learning and memory abilities, the cortical electrical activity, changes of hippocampal structure and the NMDAR subunits expressions. ResultsResults found that the rats in the 10mW/cm2 group showed the decline of spatial learning and memory abilities and EEG disorders (the decrease of EEG frequencies, and increase of EEG amplitudes and delta wave powers). Moreover, changes of basic structure and ultrastructure of hippocampus also found in the 10 and 5mW/cm2 groups. The decrease of NR 2A, 2B and p-NR2B might contribute to the impairment of cognitive functions. ConclusionsOur findings suggested that the continuous microwave exposure could cause the dose-dependent long term impairment of spatial learning and memory, the abnormalities of EEG and the hippocampal structure injuries. The decrease of NMDAR key subunits and phosphorylation of NR 2B might contribute to the cognitive impairment.

Temporal Organization of the Sleep-Wake Cycle under Food Entrainment in the Rat.

To analyze the temporal organization of the sleep-wake cycle under food entrainment in the rat. Eighteen male Sprague-Dawley rats were chronically implanted for polysomnographic recording. During the baseline (BL) protocol, rats were recorded under a 12:12 light-dark (LD) schedule in individual isolation chambers with food and water ad libitum. Food entrainment was performed by means of a 4-h food restriction (FR) protocol starting at photic zeitgeber time 5. Eight animals underwent a 3-h phase advance of the FR protocol (A-FR). We compared the mean curves and acrophases of wakefulness, NREM sleep, and REM sleep under photic and food entrainment and after a phase advance in scheduled food delivery. We further evaluated the dynamics of REM sleep homeostasis and the NREM sleep EEG delta wave profile. A prominent food-anticipatory arousal interval was observed after nine or more days of FR, characterized by increased wakefulness and suppression of REM sleep propensity and dampening of NREM sleep EEG delta activity. REM sleep exhibited a robust nocturnal phase preference under FR that was not explained by a nocturnal REM sleep rebound. The mean curve of sleep-wake states and NREM sleep EEG delta activity remained phase-locked to the timing of meals during the A-FR protocol. Our results support the hypothesis that under food entrainment, the sleep-wake cycle is coupled to a food-entrainable oscillator (FEO). Our findings suggest an unexpected interaction between FEO output and NREM sleep EEG delta activity generators.

Photoperiod Alters Duration and Intensity of Non–Rapid Eye Movement Sleep Following Immune Challenge in Siberian Hamsters (Phodopus sungorus)

Sleep is regulated by circadian and homeostatic processes, but can be altered by infectious disease. During infection or exposure to inflammatory stimuli, such as bacterial lipopolysaccharide (LPS), the duration and intensity of non–rapid eye movement sleep (NREMS), as measured by electoencephalogram (EEG) delta waves (.5–4 Hz), increase. These sleep alterations are hypothesized to conserve or redirect energy for immune system activation. Many vertebrates exhibit seasonal changes in immune function and sleep-wake cycle, and photoperiod (day length) serves as a reliable environmental cue. For example, winter is energetically demanding for most animals, and Siberian hamsters (Phodopus sungorus) adapted to short winter day lengths display reduced fever after LPS administration to presumably conserve energy. We hypothesized that short days increase the duration and intensity of NREMS after LPS challenge to create additional energy savings, despite evidence to the contrary that high fever is associated with increased NREMS. Male hamsters were housed under long (16 h light (L):8 h dark (D)) or short (8L:16D) day lengths, and chronically implanted with transmitters that recorded EEG and electromyogram (EMG) biopotentials simultaneously or core body temperature. After >10 wks in photoperiod conditions, hamsters received an i.p. injection of LPS or saline (control), and vigilance states (duration and distribution of NREMS, rapid eye movement sleep (REMS), and wakefulness) and EEG delta power spectra (NREMS intensity) were assessed. As expected, LPS treatment increased the duration and intensity of NREMS compared to controls. Hamsters adapted to short photoperiods exhibited cumulatively larger increases in NREMS duration and EEG delta wave amplitude 0–8 h after LPS injection compared to long-day LPS-treated hamsters despite short-day attenuation of fever. These results suggest a seasonal decoupling of LPS-induced fever with sleep to promote energy conservation during predictable energy shortages. Ultimately, the combination of increased sleep and reduced fever could represent a suite of physiological adaptations that increase the probability of surviving winter. (Author correspondence: Noah.Ashley@osumc.edu)

Partial Recovery of Alcohol Dependence-Related Deficits in Sleep Evoked Potentials Following 12 Months of Abstinence

Stimuli presented during sleep can produce an evoked EEG delta wave referred to as a K-complex. These responses occur when large numbers of cortical cells burst fire in a synchronized manner. Large amplitude synchronized scalp responses require that the CNS contain large numbers of healthy neurons that are interconnected with highly functional white matter pathways. The P2, N550, and P900 components of the evoked K-complex are sensitive measures of normal healthy brain aging, showing a decrease in amplitude with age. N550 and P900 amplitudes are also reduced in recently detoxified alcoholics, most dramatically over frontal scalp regions. The present study tested the hypothesis that the amplitude of K-complex related evoked potential components would increase with prolonged abstinence. Fifteen alcoholics (12 men) were studied twice, separated by a 12 month period, during which time they were followed with monthly phone calls. Subjects were aged between 38 and 60 years at their first study. They had on average a 29.3 ± 6.7 year drinking history and had been abstinent for between 54 and 405 days at initial testing. Evoked K-complexes were identified in the EEG and averaged to enable measurement of the P2, N550 and P900 peaks. Data were collected from seven scalp sites (FP1, FP2, Fz, FCz, Cz, CPz, and Pz). N550 and P900 amplitudes were significantly higher after 12 months of abstinence and an improvement of at least 5 μV occurred in 12 of the 15 subjects. N550 and P900 also showed highly significant site by night interactions with the largest increases occurring over prefrontal and frontal sites. The data indicate that the sleep evoked response may provide a sensitive marker of brain recovery with abstinence from alcohol.

Editorial [Hot Topic: Local Use-Dependent Sleep ( Guest Editors: J.M. Krueger &amp; J.P. Wisor)

A new view of the brain organization of sleep has initiated a paradigm shift in sleep research. The new paradigm views sleep as an emergent property of the collective output of smaller functional units within the brain [1-4]. State oscillations between two or more patterns of neuronal activity, one exhibiting properties of sleep and another properties of wakefulness, occur within small neuronal networks (also called neuronal assemblies or neuronal groups) such as cortical columns [5]. The sleep-like state of neuronal networks shares many properties of whole organism sleep, including homeostasis, activity-dependence, and altered or impaired functioning in pathological conditions. State oscillations also occur within individual neurons, e.g. up- and down-states, and may contribute to network oscillations [6]. This view of sleep being initiated at a local level in response to local brain activity stands in contrast to the prevailing view that sleep is imposed on the brain by sleep regulatory networks. There are multiple reviews and books devoted to the latter idea [7-11]. In contrast, the local use-dependent view of sleep has yet to be the subject of an integrated journal issue. The new local sleep paradigm is derived from many disciplines and research approaches. Clinical observations by neurologists indicated that patients behaved at times as if they were partially awake and partially asleep [12]. The developmental literature demonstrated use-dependency of the regional development of EEG patterns [13] and sleep-dependency of local plastic events [14, 15]. The learning and memory literature showed that specific learning-associated neuronal firing patterns are repeated during subsequent sleep in neural structures necessary for learning [16]; these data provide evidence for both use-dependence and local tuning of sleep-related neuronal activity. The comparative animal literature described EEG patterns indicative of half of the brain being asleep and half being awake in marine mammals [17, 18]. Human studies involving either multiple electrode EEG techniques or various imaging methods concluded that within the brain sleep unfolds regionally [19, 20]. Experimental imaging studies suggested that metabolism in specific brain regions during sleep varies in proportion to their metabolic load during prior waking activity [21, 22]. Clinical imaging studies of patients with insomnia indicated parts of the brain were activated while other parts had lower metabolic rates characteristic of sleep [23]. Electrophysiological studies suggested a local source for EEG slow wave activity [24]. Those working on the biochemistry of sleep regulation provided evidence that cellular production of substances involved in sleep regulation (e.g., adenosine, tumor necrosis factor) are use-dependent, and that they act to induce regional state-specific EEG patterns in proportion to regionally-driven sleep need [2, 25-28]. Excessive activation of discrete locations within the cerebral cortex during waking results in higher EEG delta wave amplitudes during subsequent sleep in these locations relative to nearby areas [29-31]. Characterization of individual cortical columns using evoked response potentials directly demonstrated that the columns oscillate between states resembling sleep and wakefulness in parallel with changes in blood flow [5]. At the theoretical level, state instability and poor performance associated with sleep deprivation can be viewed as a result of an increasing number of neuronal assemblies switching to sleep-like states and thereby reducing the performance fidelity of multiple assemblies needed for the task at hand [32]. Mathematical modeling efforts have contributed to the idea that whole animal sleep is a self-organizing, emergent property of the collective actions of small units in brain [33] – thereby suggesting that sleep is indeed self-organizing and a property of any viable neuronal network. The model in which sleep is imposed on the brain by subcortical sleep regulatory centers is of limited utility in explaining many sleep-related phenomena, including homeo-static regulation of sleep slow-wave activity, sleep inertia, parasomnias, sleep loss-induced performance decrements and sleep reorganization after brain lesions. The paradigm represented by the articles in this issue offers testable hypotheses for the mechanisms underlying these phenomena Despite the significant potential of and the extensive experimental support for the new paradigm, and the fact that almost all of those responsible for these developments remain professionally active, there has not been a collection of essays focused on the new paradigm and its clinical and neuro-biological manifestations. In this issue, many of those who contributed to the foundations of change review their observations within the context of the current literature and reflect on the consequences of their work for clinical and experimental biomedical science.

Localized Suppression of Cortical Growth Hormone-Releasing Hormone Receptors State-Specifically Attenuates Electroencephalographic Delta Waves

Growth hormone-releasing hormone (GHRH) promotes non-rapid eye movement sleep (NREMS), in part via a well characterized hypothalamic sleep-promoting site. However, GHRH may also act in the cortex to influence sleep. Application of GHRH to the surface of the cortex changes electroencephalographic (EEG) delta power. GHRH and the GHRH receptor (GHRHR) mRNAs are detectable in the rat cortex, and the expression of cortical GHRHR is activity dependent. Here, we microinjected a GHRH antagonist or GHRHR small interfering RNA (siGHRHR) onto the somatosensory cortex surface in rats. The unilateral application of the GHRH antagonist ipsilaterally decreased EEG delta wave power during NREMS, but not wakefulness, during the initial 40 min after injection. Similarly, the injection of siGHRHR reduced cortical expression of GHRHR and suppressed NREMS EEG delta wave power during 20-24 h after injection. Using the fura-2 calcium imaging technique, cultured cortical cells responded to GHRH by increasing intracellular calcium. Approximately 18% of the GHRH-responsive cells were GABAergic as illustrated by glutamic acid decarboxylase-67 (GAD67) immunostaining. Double labeling for GAD67 and GHRHR in vitro and in vivo indicated that only a minority of cortical GHRHR-containing cells were GABAergic. Our data suggest that endogenous cortical GHRH activates local cortical cells to affect EEG delta wave power state-specifically. Results are also consistent with the hypothesis that GHRH contributes to local network state regulation.

P.1.b.003 Is diurnal variation in plasma brain-derived neurotrophic factor level sex-related?

A 24 h polysomnographic recording was performed in a patient with sleeping sickness presenting an atypical neurological syndrome. Trypanosoma gambiense was found in a lymph gland puncture and the CSF, and a serologic immunofluorescence test was positive. The scoring technique of the polygraphic traces had to be adapted because of the presence of a permanent EEG delta wave activity during the NREM sleep stages, and the method used by Schwartz and Escande (1970) was applied. REM sleep and wakefulness presented normal polygraphic characteristics. The patient had 8 sleep episodes throughout the recording period, occurring during the daytime and at night, forming the classical diurnal sleepiness and nocturnal restlessness of sleeping sickness. All but one episode represented 1–3 complete REM-NREM sleep cycles. On all occasions, REM latency was short and 2 SOREM episodes were observed. The nychthemeral organization of the stages of vigilance differed from one state to another. Wakefulness and REM sleep had a circadian rhythmicity, while NREM sleep, total sleep time and deep sleep (corresponding to stages 3 and 4) had an ultradian periodicity. The concordance between the higher pressure for wakefulness and lower pressure for sleep around 20.00 h defined the time of occurence of a ‘forbidden zone⌉ for sleep.

Spontaneous and influenza virus-induced sleep are altered in TNF-α double-receptor deficient mice

Tumor necrosis factor-alpha (TNF-alpha) is associated with sleep regulation in health and disease. Previous studies assessed sleep in mice genetically deficient in the TNF-alpha 55-kDa receptor. In this study, spontaneous and influenza virus-induced sleep profiles were assessed in mice deficient in both the 55-kDa and 75-kDa TNF-alpha receptors [TNF-2R knockouts (KO)] and wild-type (WT) strain controls. Under baseline conditions the TNF-2R KO mice had less non-rapid eye movement sleep (NREMS) than WTs during the nighttime and more rapid eye movement sleep (REMS) than controls during the daytime. The differences between nighttime maximum and daytime minimum values of electroencephalogram (EEG) delta power during NREMS were greater in the TNF-2R KO mice than in WTs. Viral challenge (mouse-adapted influenza X-31) enhanced NREMS and decreased REMS in both strains roughly to the same extent. EEG delta power responses to viral challenge differed substantially between strains; the WT animals increased, whereas the TNF-2R KO mice decreased their EEG delta wave power during NREMS. There were no differences between strains in body temperatures or locomotor activity in uninfected mice or after viral challenge. Analyses of cortical mRNAs confirmed that the TNF-2R KO mice lacked both TNF-alpha receptors; these mice also had higher levels of orexin mRNA and reduced levels of the purine P2X7 receptor compared with WTs. Results reinforce the hypothesis that TNF-alpha is involved in physiological sleep regulation but plays a limited role in the acute-phase response induced by influenza virus.

Growth hormone-releasing hormone: cerebral cortical sleep-related EEG actions and expression

Growth hormone-releasing hormone (GHRH), its receptor (GHRHR), and other members of the somatotropic axis are involved in non-rapid eye movement sleep (NREMS) regulation. Previously, studies established the involvement of hypothalamic GHRHergic mechanisms in NREMS regulation, but cerebral cortical GHRH mechanisms in sleep regulation remained uninvestigated. Here, we show that unilateral application of low doses of GHRH to the surface of the rat somatosensory cortex ipsilaterally decreased EEG delta wave power, while higher doses enhanced delta power. These actions of GHRH on EEG delta wave power occurred during NREMS but not during rapid eye movement sleep. Further, the cortical forms of GHRH and GHRHR were identical to those found in the hypothalamus and pituitary, respectively. Cortical GHRHR mRNA and protein levels did not vary across the day-night cycle, whereas cortical GHRH mRNA increased with sleep deprivation. These results suggest that cortical GHRH and GHRHR have a role in the regulation of localized EEG delta power that is state dependent, as well as in their more classic hypothalamic role in NREMS regulation.

The correlation between neurological evaluations and neurological outcome in acute encephalitis: A hospital-based study

Acute encephalitis is a common CNS infectious disease in children. However, there are limited studies concerning about the correlation between the clinical evaluations and neurological outcome. To investigate the value of neurological evaluations, and the correlation between these evaluations and neurological outcomes of acute encephalitis, in the present study we retrospectively evaluated the neurological outcome of 0- to 16-year-old children with encephalitis or meningoencephalitis between 1999 and 2000. Of 101 children enrolled, 4 died and 25 had other neurological sequelae, including epilepsy, headache, developmental delay, and emotional or behavioral changes during the 5 years of follow-up. The causative organisms in patients with neurological sequelae were herpes virus (HSV) 2/2 (100%), influenza 2/3 (67%), mycoplasma 5/12 (42%), and enterovirus 71 2/7 (29%). The important predictors for adverse outcomes were focal neurological signs, multiple seizures or status epilepticus on admission, leukopenia, focal slow waves or continuous generalized delta waves in electroencephalography (EEG), and focal cortical parenchymal hyperintensity in the magnetic resonance imaging (MRI) ( p<0.05). Patients with initial presentations of focal neurological signs, papilledema, myoclonic jerks, and status epilepticus tended to have higher incidence of abnormal findings in brain MRI, although not achieving statistic significances. In addition, children with focal spikes or continuous generalized delta waves in EEG also had higher incidence of MRI abnormalities. We conclude that brain MRI studies may be indicated in patients with focal neurological signs, intractable seizure, and focal spikes, focal delta waves, or continuous generalized delta waves in EEG. For those with MRI examinations, focal cortical hyperintensity suggests poorer neurological outcomes.

A Case Of Hyperammonemic Encephalopathy Due To Valproate And Topiramate Combination At High Doses

A 35 years old male patient was admitted for a mental and behavioral disorder during the last two months. He had been treated for intractable epilepsy with valproate for many years. Topiramate was added in the previous year without any adverse reactions. Due to increased seizure frequency, the dosages of both drugs were increased gradually. Following the adjustment of drug regimen as 2000 mgs valproate and 400 mgs topiramate daily, the patient presented an encephalopaty with prominent delta and theta waves in EEG. Either serum liver enzymes or serum valproate levels showed no abnormality, but ammonia level had had rised up to 2 folds of normal. After withdrawal of topiramate and then valproate the symptoms resolved and ammonia level fell into the normal limits. The diagnosis of hyperammonemic encephalopathy due to treatment with the combination of valproate and topiramate was supposed. In our patient, the halopathic features had extraordinarily appeared after elevation of both antiepileptic drugs to high levels, while no adverse reactions had observed with moderately low doses. While treating patients with intractable epilepsy, complications of combinations should be carefully considered in desicion making not only for initiation but also for follow-up of drug adjustments.

CDG: a new case of a combined defect in the biosynthesis of N- and O-glycans

We report on a 5.5-year-old boy with a multiple malformation syndrome and biochemical abnormalities suggesting a combined defect in the biosynthesis of Nand O-glycans. The patient was followed prenatally for intrauterine growth retardation and a finding of intestinal obstruction (double bubble sign). Born full term as the first child of healthy, non-related Czech parents without remarkable family history, his Apgar scores were 6, 6, and 7; birth weight 2,310 g; body length 45 cm; and head circumference 32.5 cm. He presented with dysmorphic features, including dolichocephaly, low hairline, high nasal bridge, thin lips, small chin, gothic palate, blepharophimosis and epicanthus, in addition to other malformations, such as arachnodactyly, unusual palmar creases, sinus sacralis, pes equinovarus, hypospadias, inguinal hernia, cryptorchidism, vesicoureteral reflux, peripheral pulmonary stenosis, and patent foramen ovale. Shortly after birth a surgical correction of intestinal malrotation and duodenal stenosis (Ladd’s syndrome) was done. Neonatal brain ultrasonography, ophthalmologic examination, a skeletal survey and an electrocardiogram were normal. Chromosome analysis was normal. Laboratory tests including serum lactate, ammonia, and immunological investigations were within normal limits. Serum biotinidase, plasma and urinary amino acids, organic acids, purines and pyrimidines, sugars, oligoand mucopolysaccharides did not reveal any pathological changes. At age 4 months, the brain ultrasonography showed hypogenesis of the posterior part of the corpus callosum (later confirmed by MRI), and abnormal EEG delta waves were noted occipitally, without epilepsy. In addition to anemia (90 g/l, normal 105–135), elevated LDH (12.7 μkat/l, normal< 4.4) and elevated transaminases (1.1–2.2 μmol/l, normal<0.8), prolonged values of APTT (39.3–45.6, normal range 31.8–35.0) and PT (13.3, normal 11.7) were found; antithrombin III and CK were within the physiological range. At 3.5 years, the boy was admitted to hospital with severe laryngopharyngitis, and at that time a screening for congenital disorders of glycosylation (CDG) was performed. Isoelectric focusing (IEF) and HPLC of serum transferrin (Tf) showed a slight increase in asialo-Tf (4.0%; reference interval, 0.0–3.0%), a marked increase in disialoTf (18.7%; reference interval, 2.5–9.8%), increased trisialo-Tf (17.8%; reference interval, 3.4–13.7%) and decreased tetrasialo-Tf (38.8%; reference interval, 43.7– 68.1%). Abnormalities of alpha1-antitrypsin (aAT) and thyroxin-binding globulin pointed to a generalised defect Z. Albahri . E. Marklova . P. Dědek Department of Pediatrics, Faculty of Medicine, Charles University, Hradec Kralove, Czech Republic