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Background It has been widely recognized that obstructive sleep apnea (OSA) is linked to cardiovascular disease. Yet, randomized controlled studies failed to demonstrate a clear cardiovascular benefit from OSA treatment, mainly because of poor adherence to continuous positive airway pressure (CPAP). To date, no prior study has assessed the effect of CPAP treatment on daytime resting heart rate, a strong predictor of adverse cardiovascular outcomes and mortality. Methods and Results We conducted a randomized controlled study in 39 participants with OSA and prediabetes, who received either in‐laboratory all‐night (ie, optimal) CPAP or an oral placebo for 2 weeks. During daytime, participants continued daily activities outside the laboratory. Resting heart rate was continuously assessed over 19 consecutive days and nights using an ambulatory device consisting of a single‐lead ECG and triaxis accelerometer. Compared with placebo, CPAP reduced daytime resting heart rate (treatment difference, −4.1 beats/min; 95% CI, −6.5 to −1.7 beats/min; P =0.002). The magnitude of reduction in daytime resting heart rate after treatment significantly correlated with the magnitude of decrease in plasma norepinephrine, a marker of sympathetic activity ( r =0.44; P =0.02), and the magnitude of decrease in OSA severity (ie, apnea‐hypopnea index [ r =0.48; P =0.005], oxygen desaturation index [ r =0.50; P =0.003], and microarousal index [ r =0.57; P Conclusions This proof‐of‐concept randomized controlled study demonstrates, for the first time, that CPAP treatment, when optimally used at night, reduces resting heart rate during the day, and therefore has positive cardiovascular carry over effects. These findings suggest that better identification and treatment of OSA may have important clinical implications for cardiovascular disease prevention. Registration URL: https:/// www.clini​caltr​ials.gov ; Unique identifier: NCT01156116.

Sleep curtailment is an endemic behavior in modern society. Well-controlled laboratory studies have shown that sleep loss in young adults is associated with increased desire for high-calorie food and obesity risk. However, the relevance of these laboratory findings to real life is uncertain. We conducted a 3 week, within-participant, intervention study to assess the effects of extended bedtimes on sleep duration and food desire under real life conditions in individuals who are at risk for obesity. Ten overweight young adults reporting average habitual sleep duration of less than 6.5 h were studied in the home environment. Habitual bedtimes for 1-week (baseline) were followed by bedtimes extended to 8.5 h for 2-weeks (intervention). Participants were unaware of the intervention until after the baseline period. Participants received individualized behavioral counseling on sleep hygiene on the first day of the intervention period. Sleep duration was recorded by wrist actigraphy throughout the study. Participants rated their sleepiness, vigor and desire for various foods using visual analog scales at the end of baseline and intervention periods. On average, participants obtained 1.6 h more sleep with extended bedtimes (5.6 vs. 7.1; P 0.001) and reported being less sleepy (P = 0.004) and more vigorous (P = 0.034). Additional sleep was associated with a 14% decrease in overall appetite (P = 0.030) and a 62% decrease in desire for sweet and salty foods (P = 0.017). Desire for fruits, vegetables and protein-rich nutrients was not affected by added sleep. Sleep duration can be successfully increased in real life settings and obtaining adequate sleep is associated with less desire for high calorie foods in overweight young adults who habitually curtail their sleep.

OBJECTIVES Sleep is regulated by circadian and homeostatic processes and is highly organized temporally. Our study was designed to determine whether this organization is preserved in patients receiving mechanical ventilation (MV) and intravenous sedation. DESIGN Observational study. SETTING Academic medical intensive care unit. PATIENTS Critically ill patients receiving MV and intravenous sedation. METHODS Continuous polysomnography (PSG) was initiated an average of 2.0 (1.0, 3.0) days after ICU admission and continued ≥ 36 h or until the patient was extubated. Sleep staging and power spectral analysis were performed using standard approaches. We also calculated the electroencephalography spectral edge frequency 95% SEF₉₅, a parameter that is normally higher during wakefulness than during sleep. Circadian rhythmicity was assessed in 16 subjects through the measurement of aMT6s in urine samples collected hourly for 24-48 hours. Light intensity at the head of the bed was measured continuously. MEASUREMENTS AND RESULTS We analyzed 819.7 h of PSG recordings from 21 subjects. REM sleep was identified in only 2/21 subjects. Slow wave activity lacked the normal diurnal and ultradian periodicity and homeostatic decline found in healthy adults. In nearly all patients, SEF₉₅ was consistently low without evidence of diurnal rhythmicity (median 6.3 [5.3, 7.8] Hz, n = 18). A circadian rhythm of aMT6s excretion was present in most (13/16, 81.3%) patients, but only 4 subjects had normal timing. Comparison of the SEF₉₅ during the melatonin-based biological night and day revealed no difference between the 2 periods (P = 0.64). CONCLUSIONS The circadian rhythms and PSG of patients receiving mechanical ventilation and intravenous sedation exhibit pronounced temporal disorganization. The finding that most subjects exhibited preserved, but phase delayed, excretion of aMT6s suggests that the circadian pacemaker of such patients may be free-running.

Human African trypanosomiasis staging follows human African trypanosomiasis diagnosis (trypanosomes in blood and/or lymph glands, trypanosome-positive). Staging determines treatment, as stage 2 medications are toxic and/or difficult to administer. It relies on cerebrospinal fluid examination: stage 1 (no cerebrospinal fluid trypanosome, trypanosome-negative; white blood cell count ≤5/µl); stage 2 (trypanosome-positive and/or white blood cell count ≥20/µl); intermediate stage (6–19 white blood cell/µl; trypanosome-negative). Lumbar puncture is repeated biannually during the 24-month post-treatment follow-up to confirm cure or detect relapse. Sleep disorders are major at stage 2, with a two-symptom polysomnographic syndrome: sleep–wake circadian disruptions; and sleep-onset rapid eye movement sleep periods. Polysomnography (PSG) was proposed as a noninvasive diagnostic tool, and 24-h PSG recordings were performed throughout a 5-year survey in Congo. Before treatment, 76 patients were included and recorded. Normal sleep–wake patterns occurred in 45 out of 47 stage 1 patients and in 16 out of 19 intermediate-stage patients. PSG syndrome was observed in seven out of ten stage 2 patients. During post-treatment follow-up, PSG syndrome occurrence indicated relapse at stage 2. Thus, noninvasive PSG may represent a valuable alternative for human African trypanosomiasis staging, especially in the post-therapeutic follow-up. The detection of a PSG syndrome would then provoke examination of the patient’s cerebrospinal fluid.

Context: Women with polycystic ovary syndrome (PCOS) are insulin resistant and have a high risk of early-onset diabetes and cardiovascular disease. Obstructive sleep apnea (OSA) has adverse cardiometabolic consequences and is highly prevalent in women with PCOS. We sought to determine whether continuous positive airway pressure (CPAP) treatment of OSA has beneficial effects on cardiometabolic function in PCOS. Methods: Laboratory polysomnography and cardiometabolic measurements including insulin sensitivity and secretion (iv glucose tolerance test); 24-h profiles of plasma catecholamines, cortisol, and leptin; and daytime profiles of blood pressure and cardiac autonomic activity (heart rate variability) were obtained at baseline and again after 8 wk of home CPAP treatment with daily usage monitoring. Results: CPAP treatment modestly improved insulin sensitivity after controlling for body mass index (P = 0.013). The change in insulin sensitivity correlated positively with CPAP use (adjusted P = 0.027) and negatively with body mass index (adjusted P = 0.003). Daytime and nighttime norepinephrine levels were decreased after CPAP (P = 0.002), and the reductions were greater with increased CPAP use (P = 0.03). Epinephrine, cortisol, and leptin levels were not changed significantly. Daytime diastolic blood pressure decreased by an average of 2.3 mm Hg after CPAP (P = 0.035). Cardiac sympathovagal balance was 44% lower (P = 0.007) after CPAP, reflecting a shift toward lower sympathetic activity. Conclusions: In young obese women with PCOS, successful treatment of OSA improves insulin sensitivity, decreases sympathetic output, and reduces diastolic blood pressure. The magnitude of these beneficial effects is modulated by the hours of CPAP use and the degree of obesity.

This paper focuses on the development of an automatic system for sleep analysis. The system proposed in this paper combines two phases needed in sleep analysis. In a first step, an artefact detection system selects the polysomnographic signals (EEG, EOG, EMG) that are not corrupted by artefacts. In a second step, relevant features are extracted from the selected signals and classified using a neural network chosen among a bank of four neural networks. The four classifiers differ one from the others by the signals used for the classification. They were learnt using information provided by different combination of signals (EEG, EEG+EOG, EEG+EMG, EEG+EOG+EMG). Thus, the complete system enables the classification to be performed using relevant features computed from artefact-free signals, without losing too many data. The performance reached by the two-steps system is 85% of accuracy, calculated on 47 night sleep recordings.

This paper describes the process of sleep/wake stage classification. It mainly focuses on the problem of selection of relevant features extracted from the polysomnographic recordings. Iterative features selection methods were applied on a large database composed of several night recordings from different healthy adults. The results showed that the use of relative power of EEG in five frequency bands enables to correctly classify 71% of the whole data base. The addition of features extracted from EOG enables to reach 75% of agreement with the expert classification, but no significant improvement was obtained when adding features extracted from EMG.

Arousal (AR) from sleep is associated with an autonomic reflex activation raising blood pressure and heart rate (HR). Recent studies indicate that sleep deprivation may affect the autonomic system, contributing to high vascular risk. Since in sleep disorders a sleep fragmentation and a partial sleep deprivation occurs, it could be suggested that the cardiovascular effects observed at AR from sleep might be physiologically affected when associated with sleep deprivation. The aim of the study was to examine the effect of sleep deprivation on cardiac arousal response in healthy subjects.Seven healthy male subjects participated in a 64 h sleep deprivation protocol. Arousals were classified into four groups, i.e.36 s,610 s,1015 s and15 s, according to their duration. Pre-AR HR values were measured during 10 beats preceding the AR onset, and the event-related HR fluctuations were calculated during the 20 beats following AR onset. As an index of cardiac activation, the ratio of highest HR in the post-AR period over the lowest recorded before AR (HR ratio) was calculated.For AR lasting less than 10 s, the occurrence of AR induces typical HR oscillations in a bimodal pattern, tachycardia followed by bradycardia. For AR lasting more than 10 s, i.e. awakenings, the pattern was unimodal with a more marked and sustained HR rise. The HR response was consistently similar across nights, during NREM and REM sleep, without difference between conditions.Overall, total sleep deprivation appeared to have no substantial effect on cardiac response to spontaneous arousals and awakenings from sleep in healthy subjects. Further studies are needed to clarify the role of chronic sleep deprivation on cardiovascular risk in patients with sleep disorders.In healthy subjects acute prolonged sleep deprivation does not affect the cardiac response to arousal.

Study objectives The hierarchical definition of arousals from sleep includes a range of physiologic responses including microarousals, delta and K-complex bursts, and variations in autonomic system. Whether patterns in slow-wave electroencephalographic activity and autonomic activation are primary forms of arousal response can be addressed by studying effects of total sleep deprivation. We therefore examined changes in arousal density during recovery sleep in healthy subjects. Design Participants spent 6 consecutive 24-hour periods in the laboratory. Nights 1 and 2 were baseline nights followed by 64-hour total sleep deprivation, then 2 consecutive recovery nights. Setting Sleep-deprivation protocol was conducted under laboratory conditions with continuous behavioral and electrophysiologic monitoring. Participants Twelve drug-free men aged 27.4 +/- 7.9 years were studied. None reported sleepiness or altered sleep-wake cycle, and none had neurologic, psychiatric or sleep disorders. Intervention N/A. Measurements and results Arousals were classified into 4 levels: microarousals, phases of transitory activation, and delta and K-complex bursts. Sleep deprivation induced changes in the density of considered arousals except phases of transitory activation, with a distinct pattern among the different types. The greatest change was found for microarousals, which showed a significant decrease in the first recovery night (P = .01), with return to baseline thereafter. A fall in K-complex and delta-burst density was noted in the first recovery night, not, however, reaching statistical significance. The phases of transitory activation rate were virtually unaffected throughout the experimental nights. Conclusions We conclude that homeostatic sleep processes exert an inhibitory effect on arousal response from sleep with a significant effect only on the microarousal density. Decreased delta and K-complex burst rates, though not significant, support the hypothesis that they may be activating processes, probably modulated by factors independent from those implicated in cortical arousal.

Study Objectives: Patients with human African trypanosomiasis (sleeping sickness) due to the inoculation of Trypanosoma brucei gambiense or rhodesiense show a major disruption of the 24-hour sleep-wake distribution, accompanied by the occurrence of sleep-onset rapid-eye-movement (REM) sleep episodes, proportional to the severity of the illness. Although animal models of human African trypanosomiasis have been developed to understand the pathogenic mechanisms leading to immune alterations, the development of an animal model featuring the alterations of endogenous biologic rhythms remains a necessity. Animals: Sprague-Dawley rats (N = 10) entrained to a 12:12-hour dark-light regimen. Interventions: Rats were infected with Trypanosoma brucei brucei AnTat 1.1E and instrumented with electrocorticographic and electromyographic electrodes. Polysomnography was recorded continuously from 2 days before infection until the animal's death. Measurements and Results: The analysis of the spontaneous sleep-wake architecture revealed an increased proportion of slow-wave sleep (SWS) and a decreased amount of wakefulness 2 days before death. Considerable sleep fragmentation was observed in the infected rats, with numerous changes in sleep-wake stages and an increased number of episodes of wakefulness and SWS. Infected rats presented a fragmented pattern of SWS and a marked reduction in the mean paradoxical-sleep (PS) latency, resulting in a considerable disruption of the PS-SWS sequences. Abnormal transitions, particularly the appearance of sleep-onset REM episodes, marked the disruption of the internal sleep structure. The electrocorticogram traces were modified during SWS, with the occurrence of abnormal hypersynchronic slow waves and a disappearance of spindles. Conclusion: The Trypanosoma brucei brucei-infected rat is a good model of the syndrome seen in human African trypanosomiasis, ie, the 24-hour disruption of the sleep-wake cycle and the occurrence of sleep-onset REM-like sleep episodes.

During the lunar month of Ramadan, Muslims abstain from eating, drinking and smoking from sunrise to sunset. We reported previously that Ramadan provokes a shortening in nocturnal total sleep time by 40 min, an increase in sleep latency, and a decrease in slow-wave sleep (SWS) and rapid eye movement (REM) sleep duration during Ramadan. During the same study, the effects of Ramadan intermittent fasting on daytime sleepiness were also investigated in eight healthy young male subjects using a quantitative waking electroencephalograph (EEG) analysis following the multiple sleep latency test (MSLT) procedure. This procedure was combined with subjective alertness and mood ratings and was conducted during four successive experimental sessions: (1) baseline (BL) 15 days before Ramadan, (2) beginning of Ramadan (R11) on the 11th day of Ramadan, (3) end of Ramadan (R25) on the 25th day of Ramadan, (4) recovery 2 weeks after Ramadan (AR). During each session, four 20-min nap opportunities (MSLTs) were given at 10:00, 12:00, 14:00 and 16:00 h and were preceded by rectal temperature readings. Nocturnal sleep was recorded before each daytime session. Subjective daytime alertness did not change in R25 but decreased in R11 at 12:00 h, and subjective mood decreased at 16:00 h, both in R11 and R25. During the MSLT, mean sleep latency decreased by an average of 2 min in R11 (especially at 10:00 and 16:00 h) and 6 min in R25 (especially at 10:00 and 12:00 h) compared with BL. There was an increase in the daily mean of waking EEG absolute power in the theta (5.5-8.5 Hz) frequency band. Significant correlations were found between sleep latency during the MSLT and the waking EEG absolute power of the fast alpha (10.5-12.5 Hz), sigma (11.5-15.5 Hz) and beta (12.5-30 Hz) frequency bands. Sleep latency was also related to rectal temperature. In conclusion, Ramadan diurnal fasting induced an increase in subjective and objective daytime sleepiness associated with changes in diurnal rectal temperature.

During the month of Ramadan intermittent fasting, Muslims eat exclusively between sunset and sunrise, which may affect nocturnal sleep. The effects of Ramadan on sleep and rectal temperature (Tre) were examined in eight healthy young male subjects who reported at the laboratory on four occasions: (i) baseline 15 days before Ramadan (BL); (ii) on the eleventh day of Ramadan (beginning of Ramadan, BR); (iii) on the twenty-fifth day of Ramadan (end of Ramadan, ER); and (iv) 2 weeks after Ramadan (AR). Although each session was preceded by an adaptation night, data from the first night were discarded. Polysomnography was taken on ambulatory 8-channel Oxford Medilog MR-9000 II recorders. Standard electroencephalogram (EEG), electro-oculogram (EOG) and electromyogram (EMG) recordings were scored visually with the PhiTools ERA. The main finding of the study was that during Ramadan sleep latency is increased and sleep architecture modified. Sleep period time and total sleep time decreased in BR and ER. The proportion of non-rapid eye movement (NREM) sleep increased during Ramadan and its structure changed, with an increase in stage 2 proportion and a decrease in slow wave sleep (SWS) duration. Rapid eye movement (REM) sleep duration and proportion decreased during Ramadan. These changes in sleep parameters were associated with a delay in the occurrence of the acrophase of Tre and an increase in nocturnal Tre during Ramadan. However, the 24-h mean value (mesor) of Tre did not vary. The nocturnal elevation of Tre was related to a 2-3-h delay in the acrophase of the circadian rhythm. The amplitude of the circadian rhythm of Tre was decreased during Ramadan. The effects of Ramadan fasting on nocturnal sleep, with an increase in sleep latency and a decrease in SWS and REM sleep, and changes in Tre, were attributed to the inversion of drinking and meal schedule, rather than to an altered energy intake which was preserved in this study.

The temporal and quantitative interrelationships between the hypothalamo-pituitary-adrenal (HPA) axis activity and the level of central arousal were studied in 10 healthy young men during daytime wakefulness. Two experimental sessions were conducted randomly between 09.00 and 18.00 h, once after nocturnal sleep and once after a night of total sleep deprivation. Spectral analysis of serial waking electroencephalography (EEG) from a short target fixation task repeated every 10 min was undertaken, along with an estimation of cortisol secretory profiles by deconvolution of plasma radioimmunoassay measures obtained from continuous blood withdrawal with regular sampling at a 10-min interval. Following nocturnal sleep, a temporal association between the HPA axis activity and the waking EEG activity was found, cortisol secretory rate following changes in frontal gamma (20–45 Hz) band power by 10 min (average R = 0.458, p < 0.001). Although it remained significant (average R = 0.276, p < 0.05), the association strength decreased significantly following total sleep deprivation (p < 0.05, Wilcoxon test). Cortisol plasma level, secretory rate and pulse amplitude were increased as well as waking EEG power in the delta (0.5–5.5 Hz), theta (5.5–8.5 Hz) and gamma frequency bands (all p values

The ultradian dynamics of the human waking EEG was studied using a short visual fixation task repeated every 10 min throughout the daytime. The EEG spectra obtained from the tasks were assessed for time effect and ultradian periodicity. Fronto-central EEG high frequency powers (22.5‐44.5 Hz) decreased at the time of the midafternoon vigilance dip (14.00‐17.00 h) along with slight concomitant increases in parietal alpha (7.5‐13.5 Hz) and delta (1‐3 Hz) powers. A slow ultradian rhythm with a 3‐4 h periodicity strongly modulated EEG power in all frequency bands between 1 and 44.5 Hz. The high frequency waking EEG may well reflect the activity of a brain arousal process underlying maintenance of the waking state probably throughout the 24 h cycle. NeuroReport 11:1‐5 & 2000 Lippincott Williams & Wilkins.

To determine whether human hypothalamo-pituitary-adrenal axis activity is related to the alertness level during wakefulness, 10 healthy young men were studied under resting conditions in the daytime (0900–1800 h) after an 8-h nighttime sleep (2300–0700 h). A serial 70-sec gaze fixation task was required every 10 min throughout the daytime experimental session. The corresponding waking electroencephalographic (EEG) segments were submitted to quantitative spectral analysis, from which EEG β activity (absolute power density in the 13–35 Hz frequency band), an index of central alertness, was computed. Blood was collected continuously through an indwelling venous catheter and sampled at 10-min intervals. Plasma cortisol concentrations were measured by RIA, and the corresponding secretory rates were determined by a deconvolution procedure. Analysis of individual profiles demonstrated a declining tendency for EEG β activity and cortisol secretory rate, with an overall temporal relationship indicated by positive and significant cross-correlation coefficients between the two variables in all subjects (average r= 0.565, P < 0.001). Changes in cortisol secretion lagged behind fluctuations in EEG β activity, with an average delay of 10 min for all the subjects. On the average, 4.6 ± 0.4 cortisol secretory pulses and 4.9 ± 0.5 peaks in EEG β activity were identified by a detection algorithm. A significant, although not systematic, association between the episodes in the two variables was found: 44% of the peaks in EEG β activity (relative amplitude, near 125%; P < 0.001) occurred during an ascending phase of cortisol secretion, cortisol secretory rates increasing by 40% (P < 0.01) 10-min after peaks in EEG β activity. However, no significant change in EEG β activity was observed during the period from 50 min before to 50 min after pulses in cortisol secretion. In conclusion, the present study describes a temporal coupling between cortisol release and central alertness, as reflected in the waking EEGβ activity. These findings suggest the existence of connections between the mechanisms involved in the control of hypothalamo-pituitary-adrenal activity and the activation processes of the brain, which undergoes varying degrees of alertness throughout daytime wakefulness.

The benefit of retraining for heart transplant recipients (HTR) is now well established. The rehabilitation of these patients can be compromised by osteopenia and bone fractures. The resting levels of parathyroid hormone (PTH) and exercise-induced increases are higher in HTR than in healthy controls. To evaluate the effect of a moderate endurance training programme on parathyroid activity, six HTR, an average of 18 months after transplant, and seven healthy sedentary controls have been studied. None of the subjects had a history of bone disease. Two exercise tests (square wave endurance exercise tests, SWEET) with identical work rates were performed before and after training. Intact PTH, ionized calcium (Ca2+), phosphorus (Pi) and pH were measured at rest, during exercise and in the recovery periods. Training consisted of a 45-min SWEET three times a week for 6 weeks. Levels of Ca2+, Pi and PTH showed a significant increase during the exercise session in both groups. Ca2+ and Pi levels decreased rapidly after the cessation of exercise whereas PTH reached a peak at the 10th min of the recovery in both groups. This increase in PTH was significantly higher in HTR than in controls. However, despite a significant improvement of total endurance work (+ 28% in HTR, +29% in controls) this endurance training had no effect on resting levels of PTH, plasma Ca2+ or Pi, nor on their exercise-induced variations. The exercise-induced decrease in pH was less pronounced after training which is evidence of training. We conclude that a short endurance training programme does not alter the moderate hyperparathyroidism of HTR. The effect of such a training programme on bone mass and bone mineral density needs now to be evaluated.

In this paper, an original method to detect sleep slow waves (SSW) in electroencephalogram (EEG) recordings is proposed. This method takes advantage of a Matching Pursuit algorithm using a dictionary reduced to Gabor functions reproducing the main targeted waveform characteristics. By describing the EEG signals in terms of SSW properties, the corresponding algorithm is able to identify waveforms based on the largest matching coefficients. The implemented algorithm was tested on a database of whole night sleep EEG recordings collected in 9 young healthy subjects where SSW have been visually scored by an expert. Besides being fully automated and much faster than visual scoring analysis, the results obtained to the proposed method were in excellent agreement with the expert with 98% of correct detections and a 77% concordance in event time position and duration. These results were superior from those of the classical method both in terms of sensibility and precision.

International audience; An automatic sleep/wake stages classifier that deals with the presence of artifacts and that provides a confidence index with each decision is proposed. The decision system is composed of two stages: the first stage checks the 20 seconds epoch of polysomnographic signals (EEG, EOG and EMG) for the presence of artifacts and selects the artifact-free signals. The second stage classifies the epoch using one classifier selected out of four, using feature inputs extracted from the artifact-free signals only. A confidence index is associated with each decision made, depending on the classifier used and on the class assigned, so that the user's confidence in the automatic decision is increased. The two-stage system was tested on a large database of 46 night recordings. It reached 85.5% of overall accuracy with improved ability to discern NREM I stage from REM sleep. It was shown that only 7% of the database was classified with a low confidence index, and thus should be re-evaluated by a physiologist expert, which makes the system an efficient decision-support tool.

This paper presents application of an automatic classification system on 53 animal polysomnographic recordings. A two-step automatic system is used to score the recordings into three traditional stages: wake, NREM sleep and REM sleep. In the first step of the analysis, monitored signals are analyzed using artifact identification strategy and artifact-free signals are selected. Then, 30sec epochs are classified according to relevant features extracted from available signals using artificial neural networks. The overall classification accuracy reached by the presented classification system exceeded 95%, when analyzed 53 polysomnographic recordings.

The classification of sleep–wake stages suffers from poor standardization in scoring criteria and heterogeneous conditioning of polysomnographic signals. To improve applicability of fully automated sleep staging, we have designed a formal classification framework to rigorously (1) select robust candidate features, (2) emulate artificial neural network classifiers, and (3) assign sleep–wake stages using flexible decision rules. An extensive database of 48 PSG records scored in 20 s epochs by two independent clinicians was used. A small subset of 2 s elementary epochs representative of each stages with unequivocal expert scores was selected to form a limited set of learning exemplars. From 16 statistical, spectral and non-linear candidate features extracted in 2 s epochs from EEG and EMG signals, a sequential forward search selected an optimal set of five features with a 22% error rate. Multiple layer perceptrons were trained from this optimal feature set while classification accuracy was assessed using the unequivocal instance subset. A simple majority vote among 10 consecutive classifier outputs ensured a final scoring resolution comparable to that of the experts. Poor classification performance was obtained for movement time, wakefulness, and intermediate sleep stages with a 36±15% error rate (Cohen's kappa 0.48±0.18). In contrast, deep and paradoxical sleep was classified with an 82% accuracy not far from inter-expert expert agreement (83±3%). Significant improvements should be expected using a larger learning set compensating for a high inter-individual variability, and decision rules incorporating more domain-knowledge. Copyright © 2009 John Wiley & Sons, Ltd.

To detail clinical and polysomnographic characteristics in patients affected with Trypanosoma brucei gambiense (Tb.g.) human African trypanosomiasis (HAT) at different stages of evolution and to measure and compare cerebrospinal fluid (CSF) levels of hypocretin-1 with narcoleptic patients and neurologic controls.Twenty-five untreated patients affected with T.b.g. HAT were included. The patients were evaluated using a standardized clinical evaluation and a specific interview on sleep complaints. Diagnosis of stages I and II and intermediate stage was performed by CSF cell count and/or presence of trypanosomes: 4 patients were classified as stage II, 13 stage I, and 8 "intermediate" stage. Seventeen untreated patients completed continuous 24-hour polysomnography. We measured CSF levels of hypocretin-1 in all patients at different stages and evolutions, and we compared the results with 26 patients with narcolepsy-cataplexy and 53 neurologic controls.CSF hypocretin-1 levels were significantly higher in T.b.g. HAT (423.2 +/- 119.7 pg/mL) than in narcoleptic patients (40.16 +/- 60.18 pg/ mL) but lower than in neurologic controls (517.32 +/- 194.5 pg/mL). One stage I patient had undetectable hypocretin levels and 1 stage II patient showed intermediate levels, both patients (out of three patients) reporting excessive daytime sleepiness but without evidence for an association with narcolepsy. No differences were found in CSF hypocretin levels between patients with HAT stages; however, the presence of major sleep-wake cycle disruptions was significantly associated with lower CSF hypocretin-1 level with a same tendency for the number of sleep-onset rapid eye movement periods.The present investigation is not in favor of a unique implication of the hypocretin system in T.b.g. HAT. However, we propose that dysfunction of the hypothalamic hypocretin region may participate in sleep disturbances observed in African trypanosomiasis.

Objective: Several factors, such as homeostatic and circadian influences, may affect the density of cortical and subcortical arousals (AR). The purpose of this study was to examine the time-of-night and the first night effect on AR response. Methods: AR were classified into microarousals (MA), phases of transitory activation (PAT), delta (D-burst) and K-complex burst (Kburst). The AR density and duration was analyzed during two consecutive nights with the analysis of sleep stage and sleep cycle in thirtysix healthy subjects. Results: D- and K-burst showed a trend toward progressive decline across sleep cycles (p < 0.0001). While MA rate was unaffected throughout sleep cycles, PAT index increased across the night (p = 0.002). The density and duration of each group of AR exhibited reproducibility without significant differences between nights. An individual inter-night variability in AR density was found independently of night and sleep structure. Conclusions: While homeostatic and circadian influences affect nighttime subcortical and MA responses, a wakefulness drive modulates the occurrence of AR with movements. Although the pattern of AR responses was highly reliable from the first to second night, the substantial inter-individual variability suggests the existence of an individual susceptibility. Significance: The first night effect on arousal response is affected by individual susceptibility and circadian and homeostatic influences. 2008 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

This open study evaluates the effect of agomelatine, a melatonergic receptor agonist and 5-HT2C antagonist antidepressant, on sleep architecture in patients suffering from major depressive disorder. Fifteen outpatients with a baseline HAMD scoreor = 20 were treated with 25 mg/d agomelatine for 42 d. Polysomographic studies were performed at baseline, day 7, day 14, and day 42. Sleep efficiency, time awake after sleep onset and the total amount of slow-wave sleep (SWS) increased at week 6. The increase of SWS was predominant during the first sleep cycle. The amount of SWS decreased throughout the first four sleep cycles from day 7 and delta ratio increased from day 14 onwards. No change in rapid eye movement (REM) latency, amount of REM or REM density was observed and agomelatine was well tolerated. In conclusion agomelatine improved sleep continuity and quality. It normalized the distribution of SWS sleep and delta power throughout the night.

International audience; This paper focuses on the problem of selecting relevant features extracted from human polysomnographic (PSG) signals to perform accurate sleep/wake stages classification. Extraction of various features from the electroencephalogram (EEG), the electro-oculogram (EOG) and the electromyogram (EMG) processed in the frequency and time domains was achieved using a database of 47 night sleep recordings obtained from healthy adults in laboratory settings. Multiple iterative feature selection and supervised classification methods were applied together with a systematic statistical assessment of the classification performances. Our results show that using a simple set of features such as relative EEG powers in five frequency bands yields an agreement of 71% with the whole database classification of two human experts. These performances are within the range of existing classification systems. The addition of features extracted from the EOG and EMG signals makes it possible to reach about 80% of agreement with the expert classification. The most significant improvement on classification accuracy is obtained on NREM sleep stage I, a stage of transition between sleep and wakefulness.

Human African trypanosomiasis (HAT), due to the transmission of Trypanosoma brucei (T. b.) gambiense and T. b. rhodesiense by tsetse flies, is re-emerging in inter-tropical Africa. It evolves from the hemolymphatic Stage I to the meningo-encephalitic Stage II. The latter is generally treated with melarsoprol, an arseniate provoking often a deadly encephalopathy. A precise determination of the HAT evolution stage is therefore crucial. Stage II patients show: (i) a deregulation of the 24-h distribution of the sleep-wake alternation; (ii) an alteration of the sleep structure, with frequent sleep onset rapid eye movement (REM) periods (SOREMPs). Gambian HAT was diagnosed in eight patients (four, Stage II; three, Stage I; one, "intermediate" case) at the trypanosomiasis clinic at Viana (Angola). Continuous 48-h polysomnography was recorded on Oxford Medilog 9000-II portable systems before and after treatment with melarsoprol (Stage II) or pentamidine (Stage I and "intermediate" stage). Sleep traces were visually analyzed in 20-s epochs using the PRANA software. Stage II patients showed the complete sleep-wake syndrome, partly reversed by melarsoprol 1 month later. Two Stage I patients did not experience any of these alterations. However, the "intermediate" and one Stage I patients exhibited sleep disruptions and/or SOREMPs, persistent after pentamidine treatment. Polysomnography may represent a diagnostic tool to distinguish the two stages of HAT. Especially, SOREMPs appear shortly after the central nervous system invasion by trypanosomes. The reversibility of the sleep-wake cycle and sleep structure alterations after appropriate treatment constitutes the basis of an evaluation of the healing process.

Modafinil is a wake-promoting agent that affects hypothalamic structures involved in the homeostatic and circadian regulation of vigilance. Administered during sleep deprivation, it reduces the need for prolonged recovery sleep and decreases the rebound in EEG slow-wave activity. These diachronic effects suggest an action of modafinil on a homeostatic sleep regulatory process.The aim of this study was to determine whether modafinil, in comparison to the d-amphetamine reference psychostimulant and to placebo, interferes with the vigilance regulatory processes reflected in the EEG during waking.Thirty-three healthy subjects were investigated during 60 h of sustained wakefulness in a double-blind placebo-controlled parallel-design study. A 4-min maintenance-of-wakefulness test administered hourly allowed the concomitant assessment of alertness and waking EEG activity. The effects of equipotent psychostimulant dosages (modafinil 300 mg and d-amphetamine 20 mg) were evaluated at the beginning of the first sleep deprivation night, at the end of the second sleep deprivation night and in the afternoon preceding the first recovery night.One hour following ingestion, both psychostimulants increased alertness during 10-12 h, independently of the time of administration. At the level of the waking EEG, d-amphetamine attenuated the natural circadian rhythm of the different frequency bands and suppressed the sleep deprivation-related increase in low frequency (0.5-7 Hz) powers. In contrast, modafinil, which exhibited a transient amphetamine-like effect, had slight effect on circadian rhythms. Its selective action was characterized by maintenance of the alpha(1) (8.5-11.5 Hz) EEG power, which under placebo exhibited a homeostatic decrease paralleling that of alertness with a circadian trough at night.These findings demonstrate that the alertness-promoting effects of modafinil and d-amphetamine involve distinct EEG activities and do not reside on the same vigilance regulatory processes. While d-amphetamine inhibits the expression of a sleep-related process, probably through a direct cortical activation masking EEG circadian rhythms, modafinil, through a synchronic effect, preferentially disrupts the homeostatic down-regulation of a waking drive.

The aim of this study was to determine the effect of sleep deprivation on the 24-h profile of aldosterone and its consequences on renal function. Aldosterone and its main hormonal regulatory factors, ACTH (evaluated by cortisol measurement) and the renin-angiotensin system [RAS, evaluated by plasma renin activity (PRA) measurement] were determined every 10 min for 24 h in eight healthy subjects in the supine position, once with nocturnal sleep and once during total 24-h sleep deprivation. Plasma Na(+) and K(+) were measured every 10 min in four of these subjects. In an additional group of 13 subjects under enteral nutrition, diuresis, natriuresis and kaliuresis were measured once during the sleep period (23.00--07.00 h) and once during a 23.00--07.00 hours sleep deprivation period. During sleep deprivation, aldosterone displayed lower plasma levels and pulse amplitude in the 23.00--07.00-hour period than during sleep. Similarly, PRA showed reduced levels and lower pulse frequency and amplitude. Plasma cortisol levels were slightly enhanced during sleep deprivation. Overnight profiles of plasma K(+) and Na(+) were not affected. Diuresis and kaliuresis were not influenced by sleep deprivation. In contrast, natriuresis significantly increased during sleep deprivation. This study demonstrates that sleep deprivation modifies the 24-h aldosterone profile by preventing the nocturnal increase in aldosterone release and leads to altered overnight hydromineral balance.

Paradoxical sleep (PS), in which periods with (phasic) and without (tonic) rapid eye movements are intermingled, is hypothesized to be related to cognitive processing and dreaming. Based on polysomnographic data from 12 healthy subjects, this study focuses on the spectral differentiation between phasic and tonic periods. Phasic PS periods exhibited decreased theta and alpha power in the posterior brain areas suggesting the interference of visual processing related to dream imagery. Phasic PS periods were also characterized by a shift from beta to gamma activity in frontal, central and occipital areas reflecting specific phasic related activation. Together, these findings bring new evidence for the existence of visual imagery and cognitive processing during phasic PS.

To determine whether the 24-h intact PTH (iPTH) profile is influenced by the sleep-wake cycle, and whether iPTH pulses show a temporal relationship with internal sleep structure, eight normal young men were studied during 24 h under basal conditions, once with normal nighttime sleep from 2300-0700 h and once after a night of sleep deprivation followed by an 8-h period of daytime sleep from 0700-1500 h. During the 8-h nighttime sleep period, mean iPTH levels were significantly increased by +13% and mean iPTH pulse amplitudes by +31% as compared with the 8-h subsequent waking periods. During the 8 h of total sleep deprivation, mean iPTH levels were not significantly different from the corresponding period in nighttime sleep condition, but mean iPTH pulse amplitudes were significantly lower (P0.01). The 8-h daytime sleep period was associated with increased mean iPTH levels and mean iPTH pulse amplitudes (+15% and +57%, respectively, as compared with the corresponding period in nighttime sleep condition). The number of pulses was similar in both experimental series and was not influenced by sleep or by time of day. Analysis of coincidence between iPTH pulses, plasma ionized calcium and plasma phosphate pulses, and slow wave sleep, as well as with rapid eye movement sleep episodes, did not reveal any significant association. Cross-correlation analysis between iPTH, plasma ionized calcium, and plasma phosphate fluctuations during sleep also showed no systematic association. Seven other subjects were studied during a nighttime sleep period in which temporal relationships between iPTH and internal sleep structure were reevaluated using spectral analysis of the sleep electroencephalogram. Cross-correlation analysis between iPTH levels and delta-relative power fluctuations showed nonsignificant results, which confirms the lack of relationship with slow wave sleep. This study demonstrates that the iPTH 24-h profile is influenced by sleep processes with a weak circadian component. However, iPTH pulses are not temporally linked with sleep electroencephalographic activity nor with calcemia and phosphatemia fluctuations. This evidence raises questions about the origin of iPTH pulses.

After sleep deprivation, the blunting of the normal sleep-related growth-hormone (GH) pulse is compensated during the day. Consequently, the amount of GH secreted during a 24 h period is similar whether or not a person has slept during the night. These results argue against the belief that sleep disorders in children can inhibit growth through a daily GH deficit.

To determine the effect of a phase shift in sleep on the circadian clock, thyroid-stimulating hormone (TSH), cortisol, and melatonin, three robust markers of the circadian clock, were analyzed using a 10-min blood sampling procedure. In an initial experiment eight subjects were studied during two experimental sessions: once under baseline conditions with normal nighttime sleep from 2300 to 0700 (baseline) and once after a night of sleep deprivation followed by daytime sleep from 0700 to 1500 ( day 1). In a second experiment, carried out on seven subjects, the 24-h hormone profiles of the first day ( day 1) were compared with those of the second day ( day 2) of the sleep shift. During the night of sleep deprivation ( day 1) the TSH surge was higher than during baseline conditions, whereas melatonin and cortisol rhythms remained unaffected. On day 2 the amplitude of the nocturnal TSH surge was reduced in comparison to day 1, whereas the amplitudes of melatonin and cortisol rhythms were unchanged. There was a clear phase shift in the three endocrine rhythms. Triiodothyronine levels were slightly higher in the morning after the first night of sleep deprivation. These results demonstrate that 2 consecutive days of sleep shift are sufficient to affect the timing of the commonly accepted circadian markers, suggesting the existence of a rapid resetting effect on the circadian clock. TSH reacts in a distinctive manner to the sleep-wake cycle manipulation by modulating the amplitude of the nocturnal surge. This amplitude modulation is probably an integral part of the phase-shifting mechanisms controlled by the circadian clock.

We have previously described a temporal relationship between plasma cortisol pulses and slow-wave sleep and, more recently, an inverse significant cross-correlation between cortisol secretory rates and delta wave activity of the sleep electroencephalogram (EEG). The aim of this study was to observe ACTH, cortisol, and sleep delta wave activity variations throughout 24 h to get a better insight into their initiating mechanisms. Two groups of 10 subjects participated in a 24-h study, one group with a night sleep (2300–0700) and the other with a day sleep (0700–1500). Cortisol secretory rates were calculated by a deconvolution procedure from plasma levels measured at 10-min intervals. Delta wave activity was computed during sleep by spectral analysis of the sleep EEG. When delta waves and cortisol were present at the same time at the end of the night sleep as well as during the daytime sleep, they were negatively correlated, cortisol changes preceding variations in delta wave activity by ∼10 min. Increases in delta wave activity occurred in the absence of cortisol pulses, as observed at the beginning of the night. Cortisol pulses occurred without any concomitant variations of sleep delta wave activity, as observed during wakefulness and intrasleep awakenings. In no case did delta wave activity increase together with an increase in cortisol secretory rates. In conclusion, cortisol secretion and delta wave activity have independent generators. They can oscillate independently from each other, but when they are present at the same time, they are oscillating in phase opposition.

Studies have shown that both nicotine and sleep spindles are associated with enhanced memorisation. Further, a few recent studies have shown how cholinergic input through nicotinic and muscarinic receptors can trigger or modulate sleep processes in general, and sleep spindles in particular. To better understand the interaction between nicotine and sleep spindles, we compared in a single blind randomised study the characteristics of sleep spindles in 10 healthy participants recorded for 2 nights, one with a nicotine patch and one with a sham patch. We investigated differences in sleep spindle duration, amplitude, intra-spindle oscillation frequency and density (i.e. spindles per min). We found that under nicotine, spindles are more numerous (average increase: 0.057 spindles per min; 95% confidence interval: [0.025-0.089]; p = .0004), have higher amplitude (average amplification: 0.260 mu V; confidence interval: [0.119-0.402]; p = .0032) and last longer (average lengthening: 0.025 s; confidence interval: [0.017-0.032]; p = 2.7e-11). These results suggest that nicotine can increase spindle activity by acting on nicotinic acetylcholine receptors, and offer an attractive hypothesis for common mechanisms that may support memorisation improvements previously reported to be associated with nicotine and sleep spindles.