Optimization of sigma amplitude threshold in sleep spindle detection

Sleep spindles are transient EEG waveforms of non-rapid eye movement sleep. There is considerable intersubject variability in spindle amplitudes. The problem in automatic spindle detection has been that, despite this fact, a fixed amplitude threshold has been used. Selection of the spindle detection threshold value is critical with respect to the sensitivity of spindle detection. In this study a method was developed to estimate the optimal recording-specific threshold value for each all-night recording without any visual scorings. The performance of the proposed method was validated using four test recordings each having a very different number of visually scored spindles. The optimal threshold values for the test recordings could be estimated well. The presented method seems very promising in providing information about sleep spindle amplitudes of individual all-night recordings.     

Diurnal preference, sleep habits, circadian sleep propensity and melatonin rhythm in healthy human subjects

We studied the in vitro effects of ethanol (25, 50 and 100 mM) on pyroglutamyl aminopeptidase activity (pGluAP), which has been reported as thyrotrophin-releasing-hormone-degrading activity. pGluAP was measured in presence or absence of calcium, under basal and K(+)-stimulated conditions, in synaptosomes and their incubation supernatant, using pyroglutamyl-beta-naphthylamide as substrate. In basal conditions, in synaptosomes, pGluAP was inhibited by ethanol in a calcium-independent way. In the supernatant, the response differed depending on the concentration of ethanol. Depolarization with K(+) modified pGluAP in synaptosomes and supernatant depending on the presence or not of calcium. In synaptosomes, in absence of calcium, the activity was inhibited at the highest concentrations of ethanol. In contrast, in the supernatant, under depolarizing conditions, ethanol increases pGluAP in absence of calcium. These changes may be in part responsible of the behavioural changes associated to alcohol intake.     

Diurnal preference, sleep habits, circadian sleep propensity and melatonin rhythm in healthy human subjects

After 24-h sleep deprivation, 33 healthy young subjects entered the 10/20 min ultra-short sleep–wake schedule for 26 h. Melatonin rhythm was hourly assessed simultaneously. Results indicated that morning preference was significantly correlated with habitual sleep onset (r=−0.41, P=0.04), habitual sleep offset (r=−0.52, P=0.002), melatonin peak time (r=−0.36, P=0.04), and sleep propensity onset time (r=−0.36, P=0.04). The intervals between habitual sleep mid-point and melatonin peak time and between habitual sleep mid-point and sleep propensity onset time were significantly longer in morning-preference subjects than in evening-preference subjects (P<0.05). These findings suggest that the variance of diurnal preference may be related to differences in phase relations between habitual sleep timing and the circadian pacemaker.     

Fast sleep spindle (13-15 hz) activity correlates with sleep-dependent improvement in visuomotor performance

STUDY OBJECTIVES: The relationship between memory enhancement and fast (13-16 Hz) versus slow (10-13 Hz) spindle activity during sleep was investigated. DESIGN: Standard polysomnographic recordings were conducted during an adaptation, control nonlearning, and learning night. Automatic spindle detection and measurement was utilized with visual confirmation. SETTING: Participants slept in individual, temperature-controlled bedrooms in a sleep laboratory. PARTICIPANTS: Twelve healthy student volunteers (9 women and 3 men, mean age: 22.3 years) participated. INTERVENTIONS: On the learning night, participants completed a presleep learning session on a modified version of mirror-tracing task followed by a postsleep test session. No learning or test sessions were performed on the adaptation and nonlearning nights. MEASUREMENTS AND RESULTS: Tracing time was reduced by 6.4 seconds (20.6% +/- 2.07%) from the presleep to the postsleep session. Mean amplitude and duration of fast spindles was greater on the learning night than on the nonlearning night (both P values < 0.05). Skill improvement and fast-spindle activity were positively correlated (density [r = 0.76, P < 0.01], amplitude [r = 0.69, P < 0.05], and duration [r = 0.67, P <0.05]). Significant correlations between fast-spindle activity and mirror-tracing performance were also evident for the nonlearning night. There was no significant relationship between mirror-tracing performance and slow-spindle activity on any night. CONCLUSIONS: The thalamocortical network underlying fast-spindle generation may contribute to or reflect plasticity during sleep.     

Gender differences in the circadian temperature rhythms of healthy elderly subjects: relationships to sleep quality

Body core temperature and subjective sleep quality were measured in 22 healthy elderly men and women while they lived at home and continued their normal daily activities. The acrophase of body temperature was phase-advanced by an average of 1.25 h in the older women compared to the age-matched men. Habitual bedtimes did not differ between men and women, but usual wakeup time and average sleep duration did: women awakened earlier and slept for shorter durations. Women were also less satisfied with their sleep than were the men. For the group, the acrophase of body temperature was significantly positively correlated with habitual bedtime and wakeup time. These data support the notion that age-related changes in the circadian timing system are, in large part, gender-dependent. The findings are also consistent with the hypothesis that alterations in sleep timing and quality that typically accompany aging are closely tied to age-related changes in circadian physiology.     

Temporal correlation of some endocrine circadian rhythms in elderly subjects

The aim of this chronobiological study was to investigate temporal correlations in the circadian patterns of 6 hormones, namely somatotrophic hormone (STH), prolactin (PRL), cortisol (F), aldosterone (ALD), insulin (IRI) and C-peptide (CP), assayed in systemic blood serum drawn at 07:00, 10:00, 13:00, 16:00, 19:00 and 22:00 h from an antecubital vein in 19 young subjects (aged 20-29 yr, comprising 10 males and 9 females; and 20 elderly subjects (aged 70-81 yr, comprising 10 males and 10 females). All subjects were sampled on a normal dietary sodium intake (120-140 mEq/24h) while following a social routine of diurnal activity (07:00-23:00) and nocturnal rest (23:00-07:00). Time-qualified data were analyzed by lead-lag correlation and by cosinor analysis. According to the lead-lag correlation findings, it would appear that the correlation which exists between several time-qualified series in young subjects is no longer present in elderly subjects. The circadian rhythms which were found to have lost their temporal correlations with advancing age were those between STH and IRI, STH and ALD, PRL and IRI, PRL and CP, and ALD and CP. It should be noted that the correlation between hormonal rhythms breaks down mainly on account of a peculiar age-related change in the magnitude of the circadian fluctuation. This chronological decline in amplitude led to the conclusion that the senescence of endocrine rhythmic functions is a biological phenomenon characterized by altered circadian variability.     

Age-related changes in the circadian modulation of sleep-spindle frequency during nap sleep

STUDY OBJECTIVES: Sleep spindles exhibit a clear circadian modulation in healthy younger people. During the biological night (when melatonin is secreted), spindle density and spindle amplitude are high and spindle frequency and its variability are low, as compared with the biological day. We investigated whether this circadian modulation of spindle characteristics changes with age. DESIGN: A 40-hour multiple-nap paradigm under constant-routine conditions SETTING: Chronobiology Laboratory, University Psychiatric Hospitals, Basel, Switzerland PARTICIPANTS: Seventeen younger (20-31 years) and 15 older (57-74 years) volunteers. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Whereas the circadian modulation of spindle density, amplitude, duration, and intraspindle frequency variability was not greatly affected by age, we found significant changes in the circadian modulation of spindle frequency. The pronounced circadian modulation of spindle frequency in younger, but not older, subjects was phase locked with the circadian rhythm in melatonin secretion. In the latter, circadian modulation was attenuated and tended to be advanced with respect to the timing of melatonin secretion. There was no difference between age groups in the phase of the sleep-wake cycle or that of melatonin, nor did the phase angle between them differ. Although changes in the circadian modulation of spindle frequency in older subjects were accompanied by reduced amplitude in the sleep consolidation profile, there was no significant correlation between spindle frequency and sleep consolidation. CONCLUSION: This multiple-nap protocol under constant-routine conditions revealed an age-dependent weaker coupling of the circadian rhythms of spindle frequency and sleep propensity to the circadian rhythm of melatonin secretion.     

The 3111 Clock gene polymorphism is not associated with sleep and circadian rhythmicity in phenotypically characterized human subjects

Mutations in clock genes are associated with abnormal circadian parameters, including sleep. An association has been reported previously between a polymorphism (3111C), situated in the 3'-untranslated region (3'-UTR) of the circadian gene Clock and evening preference. In the present study, this polymorphism was assessed in: (1) 105 control subjects with defined diurnal preference, (2) 26 blind subjects with free-running circadian rhythms and characterized with regard to circadian period (tau) and (3) 16 delayed sleep phase syndrome patients. The control group was chosen from a larger population (n = 484) by Horne-Ostberg questionnaire analysis, from which three subgroups were selected (evening, intermediate and morning preference). Data from sleep diaries completed by 90% of these subjects showed a strong correlation between preferred and estimated timings of sleep and wake. The mean timings of activities for the evening group were at least 2 h later than the morning group. Genetic analysis showed that, in contrast with the previously published finding, there was no association between 3111C and eveningness. Neither was there an association between 3111C and tau, nor a significant difference in 3111C frequency between the normal and delayed sleep phase syndrome groups. To assess the effect of this polymorphism on messenger RNA (mRNA) translatability, luciferase reporter gene constructs containing the two Clock polymorphic variants in their 3'-UTR were transfected into COS-1 cells and luciferase activity measured. No significant difference was observed between the two variants. These results do not support Clock 3111C as a marker for diurnal preference, tau, or delayed sleep phase syndrome in humans.     

Word recall correlates with sleep cycles in elderly subjects

Morning recall of words presented before sleep was studied in relation to intervening night sleep measures in elderly subjects. Night sleep of 30 elderly subjects aged 61-75 years was recorded. Before sleep, subjects were presented with a list of paired non-related words and cued recall was asked immediately after the morning awakening. Recall positively correlated with average duration of NREM/REM cycles, and with the proportion of time spent in cycles (TCT) over total sleep time (TST). No significant correlations were found with other sleep or wake measures. These results suggest the importance of sleep structure for sleep-related memory processes in elderly adults.     

A new quantitative automatic method for the measurement of non-rapid eye movement sleep electroencephalographic amplitude variability

The aim of this study was to arrange an automatic quantitative measure of the electroencephalographic (EEG) signal amplitude variability during non‐rapid eye movement (NREM) sleep, correlated with the visually extracted cyclic alternating pattern (CAP) parameters. Ninety‐eight polysomnographic EEG recordings of normal controls were used. A new algorithm based on the analysis of the EEG amplitude variability during NREM sleep was designed and applied to all recordings, which were also scored visually for CAP. All measurements obtained with the new algorithm correlated positively with corresponding CAP parameters. In particular, total CAP time correlated with total NREM variability time (r = 0.596; P < 1E‐07), light sleep CAP time with light sleep variability time (r = 0.597; P < 1E‐07) and slow wave sleep CAP time with slow wave sleep variability time (r = 0.809; P < 1E‐07). Only the duration of CAP A phases showed a low correlation with the duration of variability events. Finally, the age‐related modifications of CAP time and of NREM variability time were found to be very similar. The new method for the automatic analysis of NREM sleep amplitude variability presented here correlates significantly with visual CAP parameters; its application requires a minimum work time, compared to CAP analysis, and might be used in large studies involving numerous recordings in which NREM sleep EEG amplitude variability needs to be assessed.     

The alteration of human sleep and circadian rhythms during spaceflight

Numerous anecdotes in the past suggest the concept that sleep disturbances in astronauts occur more frequently during spaceflight than on ground. Such disturbances may be caused in part by exogenous factors, but also an altered physiological state under microgravity may add to reducing sleep quality in a spacecraft. The present investigation aims at a better understanding of possible sleep disturbances under microgravity. For the first time, experiments were conducted in which sleep and circadian regulation could be simultaneously assessed in space. Four astronauts took part in this study aboard the Russian MIR station. Sleep was recorded polygraphically on tape together with body temperature. For a comparison, the same parameters were measured during baseline periods preceding the flights. The circadian phase of body temperature was found to be delayed by about 2 h in space compared with baseline data. A free-run was not observed during the first 30 d in space. Sleep was shorter and more disturbed than on earth. In addition, the structure of sleep was significantly altered. In space, the latency to the first REM episode was shorter, and slow-wave sleep was redistributed from the first to the second sleep cycle. Several mechanisms may be responsible for these alterations in sleep regulation and circadian phase. Most likely, altered circadian zeitgebers on MIR and a deficiency in the process S of Borbély's sleep model cause the observed findings. The change in process S may be related to changes in physical activity as a result of weightlessness.     

Phase‐amplitude coupling of sleep slow oscillatory and spindle activity correlates with overnight memory consolidation

Initially independent lines of research suggest that sleep‐specific brain activity patterns, observed as electroencephalographic slow oscillatory and sleep spindle activity, promote memory consolidation and underlying synaptic refinements. Here, we further tested the emerging concept that specifically the coordinated interplay of slow oscillations and spindle activity (phase‐amplitude coupling) support memory consolidation. Particularly, we associated indices of the interplay between slow oscillatory (0.16–1.25 Hz) and spindle activity (12–16 Hz) during non‐rapid eye movement sleep (strength [modulation index] and phase degree of coupling) in 20 healthy adults with parameters of overnight declarative (word‐list task) and procedural (mirror‐tracing task) memory consolidation. The pattern of results supports the notion that the interplay between oscillations facilitates memory consolidation. The coincidence of the spindle amplitude maximum with the up‐state of the slow oscillation (phase degree) was significantly associated with declarative memory consolidation (r = .65, p = .013), whereas the overall strength of coupling (modulation index) correlated with procedural memory consolidation (r = .45, p = .04). Future studies are needed to test for potential causal effects of the observed association between neural oscillations during sleep and memory consolidation, and to elucidate ways of modulating these processes, for instance through non‐invasive brain‐stimulation techniques.     

Changes of motor cortical excitability in human subjects from wakefulness to early stages of sleep: a combined transcranial magnetic stimulation and electroencephalographic study

The effect of sleep on human motor cortical excitability was investigated by evaluating the latency and amplitude of motor evoked potentials in ten subjects using transcranial magnetic stimulation. Motor evoked potentials and electroencephalographic data were recorded simultaneously and analyzed. Recordings were performed before, during and after a sleep period. A significant decrease in motor evoked potentials amplitude and a slight change in motor evoked potentials latency were noted in the recordings during the different sleep stages with a return to baseline values on awakening. A decrease in motor cortical excitability is suggested as explaining the effect of sleep.     

Time estimation during nocturnal sleep in human subjects

It has been postulated that time estimation during nocturnal sleep in humans can be explained by an interval timing clock inside the brain. However, no systematic investigations have been carried out with respect to how the human brain perceives the passage of time during sleep. The brain mechanisms of over- or underestimation of time spent in sleep have not yet been clarified. Here, we carried out an experimental study in which 11 healthy volunteers participated in time estimation trials scheduled six times during 9 h nocturnal sleep periods, under carefully controlled conditions. The time estimation ratio (TER: a ratio of subjective passage of time to actual time interval) decreased significantly from the first to the sixth trial. Individual TER was positively correlated with slow wave sleep prior to the trial, while it was negatively correlated with REM sleep. Our results indicate that the human brain has an ability to estimate the passage of time during nocturnal sleep without referring to time cues, and that the accuracy of this function fluctuates from overestimation in the early hours of sleep to underestimation in the last hours of sleep.     

The circadian and homeostatic modulation of sleep pressure during wakefulness differs between morning and evening chronotypes

The purpose of this study was to evaluate homeostatic and circadian sleep process in 'larks' and 'owls' under daily life conditions. Core body temperature, subjective sleepiness and waking electroencephalogram (EEG) theta-alpha activity (6.25-9 Hz) were assessed in 18 healthy men (nine morning and nine evening chronotypes, 21.4 +/- 1.9 years) during a 36-h constant routine that followed a week of a normal 'working' sleep-wake schedule (bedtime: 23.30 h, wake time: 07.30 h). The phase of the circadian rhythm of temperature and sleepiness occurred respectively, 1.5 h (P = 0.01) and 2 h (P = 0.009) later in evening- than in morning-type subjects. Only morning-type subjects showed a bimodal rhythm of sleep-wake propensity. The buildup of subjective sleepiness, as quantified by linear regression, was slower in evening than in morning types (P = 0.04). The time course of EEG theta-alpha activity of both chronotypes could be closely fitted by an exponential curve. The time constant of evening types was longer than that of morning types (P = 0.03), indicating a slower increase in sleep pressure during extended wakefulness. These results suggest that both the circadian signal and the kinetics of sleep pressure buildup differ between the two chronotypes even under prior naturalistic conditions mimicking the usual working day.     

Perception of pain coincides with the spatial expansion of electroencephalographic dynamics in human subjects

The dynamics of cortex driven by painful median nerve stimulation were investigated in event-related oscillation (ERO). We applied a wavelet time-frequency analysis to differentiate the brain dynamics between painful and non-painful somatosensory stimulation. The observed pattern to pain-induced effects exhibited a stepwise decrease of frequencies over time, starting around 26 ms over somatosensory cortex at 80 Hz, intermediate oscillations at 40 and 20 Hz around 40 ms, and reaching down to 10 Hz after 160 ms. This step-wise frequency decrease of ERO, coincident with spatial shift from the contralateral somatosensory area at 80 Hz to the centro-frontal brain at 40/20 Hz and final spatial expansion to the large region of centro-parietal areas at 10 Hz, may represent the cortical processes necessary to transfer sensory information from perceptual stages to subsequent cognitive stages in consciousness.     

A study comparing circadian rhythm and sleep quality of athletes and sedentary subjects engaged in night work.]

The aim of this study was to show the resistance and persistence of the circadian rhythm of temperature (T degree) and the sleep quality of athletic subjects and sedentary subjects engaged in night work, and attempt to explain the mechanisms that influence these differences. The effects of night work on biological rhythms have been studied extensively in the past few years. The contradictory situations for the night workers irrefutably affect their biological systems. Individuals with high amplitudes in their circadian rhythms have been found to be more tolerant to shift work and this results in a greater stability of circadian rhythms. This seems beneficial in coping with frequent rhythm disturbances. The physical training program seems to improve several mechanisms of the human biological system: amplitudes of circadian rhythms were increased and the circadian rhythm period was more resistant to an environment extreme (night work, shift work, sleep deprivation, or jet lag). To test this hypothesis, athletes and sedentary subjects who were engaged in regular night work were selected in the PSA Peugeot Citro?n Automobiles Group in French Normandy country. The circadian rhythm of the T degree for both groups was studied with a specific methodology and with extensive spectral analysis, especially the spectral elliptic inverse method. Study models of the rhythm of the T degree were determined and the characteristic parameters were exposed. A complementary actigraphic study showed the physical training program's effects on the sleep quality. The results revealed a large stability in the rhythm of circadian variation of T degree for the athletes: the amplitude was still large but for the sedentary subjects the amplitude of the T degree decreased and it was difficult to adjust a period on the rhythm of T degree. The stability and persistent quality of the athletes' circadian rhythm was confirmed. We observed that the actigraphic sleep was greater for athletes than for sedentary subjects, and the acrophase time for the athletes was later than for the sedentary subjects during the night shift.     

Impact of a circadian clock on the timing of human sleep

This paper redescribes some recordings of human sleep and waking made in several laboratories during the past decade under conditions of temporal isolation. Since 1972 it has been noticed that sleep duration depends mainly on the timing of prior sleep onset relative to a rhythm of 24- to 25-h duration. The present paper emphasizes four additional points: 1) that the dependence sometimes includes a remarkable discontinuity, 2) that such dependence is characteristic of a rhythmically modulated threshold process; 3) that the rhythm's period gradually changes in some experiments; and 4) that no comparable regularity has been detected in the timing of sleep onset. This last impugns the reliability of models that treat sleep onset and wake onset as complementary but comparable processes.