FES ARAGON

Cortical oscillations in the range of alpha activity (8-13 Hz) are one of the fundamental electrophysiological phenomena of the human electroencephalogram (EEG). Evidence from quantitative EEG data has shown that their electrophysiological features, cortical generation mechanisms, and therefore, their functional correlates vary along the sleep-wake continuum. Specifically, spectral microstructure and EEG coherence levels between anterior and posterior cortical regions permit to differentiate among alpha activity spontaneously appearing in relaxed wakefulness with eyes closed, drowsiness period, and REM sleep, by reflecting distinct properties of neural networks involved in its cortical generation as well as a different interplay between cortical generators, respectively. Besides, the dissimilar spatiotemporal features of brain electrical microstates within the alpha range reveals a different geometry of active neural structures underlying each alpha variant or, simply, changes in the stability level of neural networks during each brain state. Studies reviewed in this paper support the hypothesis that two different alpha variants occur during human REM sleep: 'background responsive alpha activity', blocked over occipital regions when rapid eye movements are present, and 'REM-alpha bursts', non modulated by the alternation of tonic and phasic periods. Altogether, evidence suggests that electrophysiological features of human cortical oscillations in the alpha frequency range vary across different behavioural states, as well as within state, reflecting different cerebral phenomena with probably dissimilar functional meaning. © 2002 Éditions scientifiques et médicales Elsevier SAS alpha rhythm / alpha activity / wakefulness / drowsiness / REM / quantitative EEG techniques / spectral analysis / coherence / brain microstates / humans Résumé -Oscillations alpha au cours de l'éveil, de la somnolence et du sommeil paradoxal : différents phénomènes EEG au sein de la bande alpha. Les oscillations corticales dans la bande alpha (8-13 Hz) sont un des phénomènes électrophysiologiques fondamentaux de l'electroencephalogramme humain (EEG). L'EEG quantifié a montré que les caractéristiques electrophysiologiques, les mécanismes de genèse corticale et les corrélats fonctionnels de cette activité varient le long du continuum veille-sommeil. En particulier, la microstructure spectrale et les FLA www.elsevier.fr/direct/nc-cn niveaux de cohérence entre régions corticales antérieures et postérieures permettent de différencier l'activité alpha qui apparaît au cours de la veille calme, yeux fermés, de celle observée en stade de somnolence ou en sommeil paradoxal (REM). Ceci reflète probablement les propriétés différentes des réseaux neuronaux impliqués dans leur genèse respective, ainsi que les rapports différents entre générateurs corticaux. En dehors de cela, les aspects spatio-temporels dissimilaires des micro-états EEG dans la bande alpha mettent en évidence, soit des géométries neurales différentes sous-jacentes à chaque variante de l'alpha, soit tout simplement des changements dans la stabilité des réseaux neuronaux dans chacun des niveaux révélées par la technique des 'micro-états'. Les études revues dans cet article étayent l'hypothèse de deux variantes différentes de l'alpha au cours du sommeil paradoxal (SP) : d'une part 'l'alpha réactif de base', bloqué sur les régions occipitales dès que les mouvements rapides des yeux sont présents, d'autre part les 'bouffées alpha du SP', indifférentes à l'alternance de périodes toniques ou phasiques. Au total, l'évidence accumulée suggère une variation de l'activité dans la bande alpha non seulement au cours de différents états comportementaux, mais également au sein de chaque état, reflétant différents phénomènes cérébraux de signification fonctionnelle dissimilaire. © 2002 Éditions scientifiques et médicales Elsevier SAS rythme alpha / activité alpha / veille / somnolence / sommeil / REM / sommeil paradoxal / EEG quantifié / analyse spectrale / coherence / micro-états cérébraux / homme

Evidence suggests that sleep homeostasis is not only dependent on duration of previous wakefulness but also on experience-and/or use-dependent processes. Such homeostatic mechanisms are reflected by selective increases in the duration of a sleep stage, modifications to electrophysiological-metabolic brain patterns in specific sleep states, and/or reactivation to neuronal ensembles in subsequent sleep periods. Use-dependent sleep changes, apparently different from those changes caused by memory consolidation processes, are thought to reflect neuronal restoration processes after the sustained exposure to stimulation during the preceding wakefulness. In the present study, we investigated changes in the brain electrical activity pattern during human sleep after 6 hr of continuous auditory stimulation during previous wakefulness. Poststimulation nights showed a widespread increase of spectral power within the ␣ (8-12 Hz) and sleep spindle (12-15 Hz) frequency range during slow-wave sleep (SWS) compared with the baseline night. This effect was mainly attributable to an enhanced EEG amplitude rather than an increase of oscillations, except for temporal (within ␣ and sleep spindles) and parietal regions (within sleep spindles) in which both parameters contributed equally to the increase of spectral energy. Power increments were accompanied by a strengthening of the coherence between fronto-temporal cortical regions within a broad frequency range during SWS but to the detriment of the coherence between temporal and parieto-occipital areas, suggesting underlying compensatory mechanisms between temporal and other cortical regions. In both cases, coherence was built up progressively across the night, although no changes were observed within each SWS period. No electrophysiological changes were found in rapid eye movement sleep.

Spontaneous alpha activity clearly present in relaxed wakefulness with closed eyes, drowsiness period at sleep onset, and REM sleep was studied with spatial segmentation methods in order to determine if the brain activation state would be modulating the alpha spatial microstates composition and duration. These methods of spatial segmentation show some advantages: i) they extract topographic descriptors independent of the chosen reference (reference-free methods), and ii) they achieve spatial data reduction that are more data-driven than dipole source analysis. The results obtained with this study revealed that alpha activity presented a different spatio-temporal pattern of brain electric fields in each arousal state used in this study. These differences were reflected in a) the mean duration of alpha microstates (longer in relaxed wakefulness than in drowsy period and REM sleep), b) the number of brain microstates contained in one second (drowsiness showed more different microstates than did relaxed wakefulness and REM state), and c) the number of different classes (more abundant in drowsiness than in the rest of brain states). If we assume that longer segments of stable brain activity imply a lesser amount of different information to process (as reflected by a higher stability of the brain generator), whereas shorter segments imply a higher number of brain microstates caused by more different steps of information processing, it is possible that the alpha activity appearing in the sleep onset period could be indexing the hypnagogic imagery self-generated by the sleeping brain, and a phasic event in the case of REM sleep. Probably, REM-alpha bursts are associated with a brain microstate change (such as sleep spindles), as demonstrated by its phasic intrusion in a desynchronized background of brain activity. On the other hand, alpha rhythm could be the “baseline” of brain activity when the sensory inputs are minimum and the state is relaxed wakefulness.

Normal electroencephalographic (EEG) alpha variants appear during relaxed wakefulness with closed eyes, drowsiness period at sleep onset, and rapid eye movement (REM) sleep in bursts without arousal signals. Previous results revealed that fronto-occipital and frontofrontal alpha coherences became weaker from wakefulness to drowsiness, and finally to REM sleep. The present work was aimed at determining whether a generalized or a unidirectional deactivation of the long fronto-occipital fasciculi, previously proposed to be involved in the alpha rhythm generation, could explain the above-mentioned results. Polynomial regression analyses, applied to the change of alpha coherence with distance along the antero-posterior axis, suggested that the anterior and posterior local circuits show a similar level of activation in all brain states. Bivariate partial correlation analyses between local alpha coherences revealed that such local circuits maintain a reciprocal dependency during wakefulness, but unidirectional during drowsiness (anterior-to-posterior, A ± P) and REM sleep (posterior-toanterior, P ± A). From these findings, both anterior and posterior cortical structures are suggested as being involved in the generation of the three alpha variants. If the implication of a double cortical generation source (anterior and posterior) of alpha variants is assumed, these two generators seem to maintain a mutual inter-dependency during wakefulness, whereas during the transition to human sleep, the anterior areas work quite independently of the posterior regions. Finally, the occipital structures may be the driving force for the REM-alpha bursts generation, since involvement of frontal regions demonstrated a high dependence on the posterior neural circuits in the genesis of this sleep event. D

The functional relationships between the brain areas supposedly involved in the generation of the alpha activity were quanti®ed by means of INTRA-and INTER-hemispheric coherences during different arousal states (relaxed wakefulness, drowsiness at sleep onset, and rapid eye movement sleep) where such an activity can be clearly detectable in the human EEG. A signi®cant decrease in the fronto-occipital as well as in the inter-frontal coherence values in the alpha range was observed with the falling of the vigilance level, which suggests that the brain mechanisms underlying these coherences are state dependent. Making fronto-frontal coherence values in the alpha frequency band useful indexes to discern between brain functional states characterized by a different arousal level. q Alpha activity (7.5±12.5 Hz) is the electrophysiological correlate of a relaxed wakefulness state with closed eyes. Its brain generation sources have been proposed to be located in the occipital [10,16] and anterior regions . This brain activity is also clearly observed in the human drowsiness period at sleep onset and in the rapid eye movement (REM) stage in a burst manner . Few studies have explored the generation processes of human alpha activities appearing in other arousal states different from wakefulness. Hasan and Broughton [7] found that both the occipital and fronto-central areas played an independent role in the drowsiness-alpha generation. To our knowledge, there is no information available in the literature on the generation mechanisms of the REM-alpha bursts. However, this activity has shown different properties of brain microstates [4] and seems to be functionally different from the alpha activity contained in the REM-EEG background .

Evidence suggests that sleep architecture is affected by endogenous homeostatic mechanisms as well as by behavioral and sensory demands during the prior wakefulness. Regarding the auditory system, sensory deprivation has shown to drastically modify the sleep structure, stressing the relevance of such sensory system for sleep organization. Changes in sleep architecture following prolonged auditory stimulation during prior wakefulness would provide additional support to this hypothesis. In the present study, auditory stimulation was administered over a 6 h period prior to sleep. Sleep parameters obtained from visual scoring were quantified across the total sleep period, for each sleep cycle, and for the two halves of the night, separately. Results showed that 6 h of waking-auditory stimulation were followed by an increase in the duration of slow wave sleep, a shortening of the latency between slow wave sleep periods, and a longer sleep onset latency as compared with the baseline night. In contrast, REM sleep parameters were unaffected by the pre-sleep auditory stimulation. These results indicate that sleep architecture depends on auditory demands during the prior wakefulness, suggesting that the local neural activation underlying auditory stimulation may trigger brain control mechanisms selectively involved in both the slow wave sleep maintenance and organization.

Epidemiological and clinical data are presented on 165 cases of Venezuelan hemorrhagic fever (VHF), a newly emerging viral zoonosis caused by Guanarito virus (of the family Arenaviridae). The disease is endemic in a relatively circumscribed area of central Venezuela. Since its first recognition in 1989, the incidence of VHF has peaked each year between November and January, during the period of major agricultural activity in the region of endemicity. The majority of cases have involved male agricultural workers. Principal symptoms among the patients with VHF included fever, malaise, headache, arthralgia, sore throat, vomiting, abdominal pain, diarrhea, convulsions, and a variety of hemorrhagic manifestations. The majority of patients also had leukopenia and thrombocytopenia. The overall fatality rate among the 165 cases was 33.3%, despite hospitalization and vigorous supportive care.

Rodents collected from the Venezuelan llanos (plains) during field studies of viral hemorrhagic fever were tested for evidence of hantavirus infection. Hantavirus antibody was found in one (7.7%) of 13 Oryzomys bicolor, one (3.4%) of 29 Rattus rattus, 10 (6.0%) of 166 Sigmodon alstoni and one (2.2%) of 45 Zygodontomys brevicauda. Hantavirusspecific RNA was detected in lung tissues from four antibody-positive rodents: two S. alstoni from Portuguesa State and one S. alstoni each from Cojedes and Barinas States. A hantavirus isolate (herein identified as VHV-574) was recovered from lung tissue from a hantavirus RNA-positive S. alstoni collected from Portuguesa State. The results of serological tests and analyses of small and medium RNA segment nucleotide sequence data indicated that VHV-574 represents a novel hantavirus (proposed name 'Carlo Delgadito') that is distinct from all previously characterized hantaviruses. The results of analyses of nucleotide sequence data from the four hantavirus RNA-positive S. alstoni suggested that Carlo Delgadito virus is widely distributed in the Venezuelan llanos. © 1997 Elsevier Science B.V.

Despite intensive surveillance, Venezuelan hemorrhagic fever (VHF), caused by Guanarito (GTO) virus, has been detected in only a small region of western Venezuela. To determine whether VHF is associated with a particular regional GTO virus strain(s), 29 isolates from rodents and humans throughout the surrounding regions were analyzed by partial sequencing of the nucleocapsid protein gene. Phylogenetic trees delineated nine distinct GTO genotypes that differ by 4-17% in nucleotides and up to 9% in amino acid sequences; most appeared to be restricted to discrete geographic regions, although a few genotypes were isolated in several locations. Each genotype included at least one strain recovered from a rodent, but only two genotypes were isolated from VHF cases. The presence outside of the endemic/epidemic region of two genotypes isolated also from VHF cases suggests that human pathogenic viruses occur outside of the endemic zone, but do not frequently infect people and/or cause apparent disease there. VHF does not appear to be associated with a GTO virus genotype that is restricted to a certain rodent species. When quasispecies diversity was examined, rodent isolates had higher sequence variation than human isolates. One rodent isolate included a mixture of two phylogenetically distinct genotypes, suggesting a dual infection.

Venezuelan equine encephalitis viruses (VEEV) belonging to subtype IC have caused three (1962-1964, 1992-1993 and 1995) major equine epizootics and epidemics. Previous sequence analyses of a portion of the envelope glycoprotein gene demonstrated a high degree of conservation among isolates from the 1962-1964 and the 1995 outbreaks, as well as a 1983 interepizootic mosquito isolate from Panaquire, Venezuela. However, unlike subtype IAB VEEV that were used to prepare inactivated vaccines that probably initiated several outbreaks, subtype IC viruses have not been used for vaccine production and their conservation cannot be explained in this way. To characterize further subtype IC VEEV conservation and to evaluate potential sources of the 1995 outbreak, we sequenced the complete genomes of three isolates from the 1962-1964 outbreak, the 1983 Panaquire interepizootic isolate, and two isolates from 1995. The sequence of the Panaquire isolate, and that of virus isolated from a mouse brain antigen prepared from subtype IC strain P676 and used in the same laboratory, suggested that the Panaquire isolate represents a laboratory contaminant. Some authentic epizootic IC strains isolated 32 years apart showed a greater degree of sequence identity than did isolates from the same (1962-1964 or 1995) outbreak. If these viruses were circulating and replicating between 1964 and 1995, their rate of sequence evolution was at least 10-fold lower than that estimated during outbreaks or that of closely related enzootic VEEV strains that circulate continuously. Current understanding of alphavirus evolution is inconsistent with this conservation. This subtype IC VEEV conservation, combined with phylogenetic relationships, suggests the possibility that the 1995 outbreak was initiated by a laboratory strain.

The objective of this study was to elucidate the natural rodent host relationships of Guanarito and Pirital viruses (family Arenaviridae) in the plains of central Venezuela. Ninety-two arenavirus isolates from 607 animals, representing 10 different rodent species, were characterized to the level of serotype. The 92 isolates comprised 19 Guanarito virus strains and 73 Pirital virus strains. The 19 Guanarito virus isolates were from Zygodontomys brevicauda; 72 (98.6%) of the 73 Pirital virus isolates were from Sigmodon alstoni. These results indicate that the natural rodent associations of these 2 sympatric arenaviruses are highly specific and that Z. brevicauda and S. alstoni are the principal rodent hosts of Guanarito and Pirital viruses, respectively.

, we investigated the possible continuous circulation of epizootic Venezuelan equine encephalitis (VEE) virus suggested by a 1983 subtype IC interepizootic mosquito isolate made in Panaquire, Miranda State, Venezuela. The study area was originally covered by lowland tropical rainforest but has been converted into cacao plantations. Sentinel hamsters, small mammal trapping, mosquito collections, and human serosurveys were used to detect active or recent virus circulation. Six strains of subtype ID VEE virus were isolated from hamsters that displayed no apparent disease. Four other arboviruses belonging to group A (Togaviridae: Alphavirus), two Bunyamwera group (Bunyaviridae), and three Gamboa group (Bunyaviridae) arboviruses were also isolated from hamsters, as well as 8 unidentified viruses. Venezuelan equine encephalitis-specific antibodies were detected in 5 small mammal species: Proechimys guairae, Marmosa spp., and Didelphis marsupialis. Mosquito collections comprised of 38 different species, including 8 members of the subgenus Culex (Melanoconion), did not yield any virus isolates. Sera from 195 humans, either workers in the cacao plantation or nearby residents, were all negative for VEE virus antibodies. Sequences of 1,677 nucleotides from the P62 gene of 2 virus isolates indicated that they represent a subtype ID lineage that is distinct from all others characterized previously, and are unrelated to epizootic VEE emergence.

The genetic diversity and phylogenetic relationships of a collection of strains of dengue virus type 1 (DV-1), isolated from different parts of the world, were investigated. Phylogenetic trees derived from the complete sequence of the E gene of 44 strains suggested the existence of five genetic types defined by a maximum nucleotide divergence within each group of 6%. The 22 strains from America were classified into a single genetic type that included strains associated either with classical dengue or hemorrhagic dengue episodes. Using a maximum likelihood procedure based on a single rate with dated tips model and substitution rates calculated at the third codon position, evolution of the five DV-1 genotypes was shown to conform to a molecular clock. The average rate of evolution was estimated to be approximately 16.2 ϫ 10 Ϫ4 substitutions/ third codon position site/year. Using this estimate, divergence among the DV-1 genotypes was calculated to have occurred approximately 100 years ago. Very low average value of the ratio of nonsynonymous-to-synonymous nucleotide substitutions, relative to the respective sites (0.046), indicated that the evolution of the E gene of the DV-1 is subject mostly to purifying selection. © 2002 Elsevier Science (USA)

Pirital-like virus isolates from rodents collected in a variety of habitats within a six-state area of central Venezuela were analyzed genetically by amplifying a portion of the nucleocapsid protein gene using RT-PCR. Comparisons of the sequences from 30 selected Pirital-like virus isolates demonstrated up to 26% divergence in nucleotide sequences and up to 16% divergence in deduced amino acid sequences. Within the Pirital monophyletic group, 14 distinct lineages or genotypes, differing by at least 6% in nucleotide sequences, were identified. Although sample sizes were small for some lineages, many of the different genotypes were sampled in only one region or locality, suggesting allopatric divergence. Complement fixation tests with representatives of the most divergent Pirital virus lineages failed to delineate multiple species or subtypes within the Pirital clade. These results indicate that the previously proposed 12% nucleocapsid protein amino acid sequence divergence cutoff value for delineating arenavirus species is not appropriate for the entire family. When individual clones were examined from PCR amplicons, a mean of 0.17% sequence diversity vs the consensus sequences was detected, suggesting diverse quasispecies populations within infected rodent hosts. Possible explanations for the extreme genetic diversity within and among Pirital virus populations in infected rodents are discussed.

One of the most important questions in arbovirology concerns the origin of epidemic Venezuelan equine encephalitis (VEE) viruses; these viruses caused periodic, extensive epidemics/epizootics in the Americas from 1938-1973 (reaching the United States in 1971) but had recently been presumed extinct. We have documented the 1992 emergence of a new epidemic/epizootic VEE virus in Venezuela. Phylogenetic analysis of strains isolated during two outbreaks indicated that the new epidemic/epizootic virus(es)