Sleep deprivation and Modafinil affect cortical sources of resting state electroencephalographic rhythms in healthy young adults

Objective: It has been reported that sleep deprivation affects the neurophysiological mechanisms underpinning the vigilance. Here, we tested the following hypotheses in the PharmaCog project (www.pharmacog.org): (i) sleep deprivation may alter posterior cortical delta and alpha sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms in healthy young adults; (ii) after the sleep deprivation, a vigilance enhancer may recover those rsEEG source markers. Methods: rsEEG data were recorded in 36 healthy young adults before (Pre-sleep deprivation) and after (Post-sleep deprivation) one night of sleep deprivation. In the Post-sleep deprivation, these data were collected after a single dose of PLACEBO or MODAFINIL. rsEEG cortical sources were estimated by eLORETA freeware. Results: In the PLACEBO condition, the sleep deprivation induced an increase and a decrease in posterior delta (2–4 Hz) and alpha (8–13 Hz) source activities, respectively. In the MODAFINIL condition, the vigilance enhancer partially recovered those source activities. Conclusions: The present results suggest that posterior delta and alpha source activities may be both related to the regulation of human brain arousal and vigilance in quiet wakefulness. Significance: Future research in healthy young adults may use this methodology to preselect new symptomatic drug candidates designed to normalize brain arousal and vigilance in seniors with dementia

The Emergence of Emotions

Emotion is conscious experience. It is the affective aspect of consciousness. Emotion arises from sensory stimulation and is typically accompanied by physiological and behavioral changes in the body. Hence an emotion is a complex reaction pattern consisting of three components: a physiological component, a behavioral component, and an experiential (conscious) component. The reactions making up an emotion determine what the emotion will be recognized as. Three processes are involved in generating an emotion: (1) identification of the emotional significance of a sensory stimulus, (2) production of an affective state (emotion), and (3) regulation of the affective state. Two opposing systems in the brain (the reward and punishment systems) establish an affective value or valence (stimulus-reinforcement association) for sensory stimulation. This is process (1), the first step in the generation of an emotion. Development of stimulus-reinforcement associations (affective valence) serves as the basis for emotion expression (process 2), conditioned emotion learning acquisition and expression, memory consolidation, reinforcement-expectations, decision-making, coping responses, and social behavior. The amygdala is critical for the representation of stimulus-reinforcement associations (both reward and punishment-based) for these functions. Three distinct and separate architectural and functional areas of the prefrontal cortex (dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex) are involved in the regulation of emotion (process 3). The regulation of emotion by the prefrontal cortex consists of a positive feedback interaction between the prefrontal cortex and the inferior parietal cortex resulting in the nonlinear emergence of emotion. This positive feedback and nonlinear emergence represents a type of working memory (focal attention) by which perception is reorganized and rerepresented, becoming explicit, functional, and conscious. The explicit emotion states arising may be involved in the production of voluntary new or novel intentional (adaptive) behavior, especially social behavior

Biofeedback and drug-resistant epilepsy: Back to an earlier treatment?

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Excursions dans les Alpes-Maritimes et les Basses-Alpes : livret-guide /

Illustrated cover.Bibliography: p. 49-55

Functional connectivity and cognitive changes after donepezil treatment in healthy participants

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Late Barremian–early Aptian ammonite bioevents from the Urgonian-type series of Provence, southeast France: Regional stratigraphic correlations and implications for dating the peri-Vocontian carbonate platforms

This work provides a new ammonite age-calibration of the rudistid limestones of the Urgonian-type Provence carbonate platform (Southeast France) based on sampling along three ~200 km-long platform to-basin transects and re-examination of historical collections. Ammonite key findings indicate that the first rudistid platform stage (including the Agriopleura and requieniidemonopleurid beds) develops and spreads northward through the Toxancyloceras vandenheckii-Gerhardtia sartousiana zones interval (lower upper Barremian). This stage is interrupted by the tectonically-induced deepening of the southern Provence domain during the Imerites giraudi Zone while the northern regions records the massive deposition of PalorbitolinaeHeteraster beds. Recovery of the rudistid carbonate system is illustrated by the development of caprinid-bearing rudistid limestones in the North Provence domain through the Martelites sarasini Subzone (lower Martelites sarasini Zone, uppermost Barremian), which shows a bidirectional progradation toward the South Provence and Vocontian basins. The caprinid-bearing limestones terminate at a shortterm exposure and are overlain by chertyeoobioclastic deposits spanning the Pseudocrioceras waagenoides Subzone (upper M. sarasini Zone) to the lower Deshayesites forbesi Zone. A regional-wide flooding of the study area is illustrated by the abrupt change to a marl-dominated regime occurring in the upper D. forbesi Zone. Compared to the previous datings, the Barremian/Aptian boundary should be relocated in the lower part of the post-caprinid, chertyeoobioclastic deposits although its precise level cannot be fixed due to the lack of a continuous ammonite record. Ammonite age-calibration of the surrounding Urgonian rudistid platform series is discussed and gives evidence of a comparable twofold demise of the peri-Vocontian rudistid biota during the uppermost Barremian. Accordingly, the link between the final demise of the peri-Vocontian rudistid biota and the onset and/or culmination of the mid-early Aptian Oceanic Anoxic Event (OAE) 1a should be reconsidered

Evaluation of symptomatic drug effects in Alzheimer's disease: strategies for prediction of efficacy in humans

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Evaluation of symptomatic drug effects in Alzheimer’s disease: strategies for prediction of efficacy in humans

In chronic diseases such as Alzheimer's disease (AD), the arsenal of biomarkers available to determine the effectiveness of symptomatic treatment is very limited. Interpretation of the results provided in literature is cumbersome and it becomes difficult to predict their standardization to a larger patient population. Indeed, cognitive assessment alone does not appear to have sufficient predictive value of drug efficacy in early clinical development of AD treatment. In recent years, research has contributed to the emergence of new tools to assess brain activity relying on innovative technologies of imaging and electrophysiology. However, the relevance of the use of these newer markers in treatment response assessment is waiting for validation. This review shows how the early clinical assessment of symptomatic drugs could benefit from the inclusion of suitable pharmacodynamic markers. This review also emphasizes the importance of re-evaluating a step-by-step strategy in drug development

Evaluation of symptomatic drug effects in Alzheimer's disease: strategies for prediction of efficacy in humans.

In chronic diseases such as Alzheimer's disease (AD), the arsenal of biomarkers available to determine the effectiveness of symptomatic treatment is very limited. Interpretation of the results provided in literature is cumbersome and it becomes difficult to predict their standardization to a larger patient population. Indeed, cognitive assessment alone does not appear to have sufficient predictive value of drug efficacy in early clinical development of AD treatment. In recent years, research has contributed to the emergence of new tools to assess brain activity relying on innovative technologies of imaging and electrophysiology. However, the relevance of the use of these newer markers in treatment response assessment is waiting for validation. This review shows how the early clinical assessment of symptomatic drugs could benefit from the inclusion of suitable pharmacodynamic markers. This review also emphasizes the importance of re-evaluating a step-by-step strategy in drug development

A 15-day course of donepezil modulates spectral EEG dynamics related to target auditory stimuli in young, healthy adult volunteers

To identify possible electroencephalographic (EEG) markers of donepezil's effect on cortical activity in young, healthy adult volunteers at the group level. METHODS: Thirty subjects were administered a daily dose of either 5mg donepezil or placebo for 15days in a double-blind, randomized, cross-over trial. The electroencephalogram during an auditory oddball paradigm was recorded from 58 scalp electrodes. Current source density (CSD) transformations were applied to EEG epochs. The event-related potential (ERP), inter-trial coherence (ITC: the phase consistency of the EEG spectrum) and event-related spectral perturbation (ERSP: the EEG power spectrum relative to the baseline) were calculated for the target (oddball) stimuli. RESULTS: The donepezil and placebo conditions differed in terms of the changes in delta/theta/alpha/beta ITC and ERSP in various regions of the scalp (especially the frontal electrodes) but not in terms of latency and amplitude of the P300-ERP component. CONCLUSION: Our results suggest that ITC and ERSP analyses can provide EEG markers of donepezil's effects in young, healthy, adult volunteers at a group level. SIGNIFICANCE: Novel EEG markers could be useful to assess the therapeutic potential of drug candidates in Alzheimer's disease in healthy volunteers prior to the initiation of Phase II/III clinical studies in patients