Constant Routine Conditions Research Articles

An Improved Method for Estimating Human Circadian Phase Derived From Multichannel Ambulatory Monitoring and Artificial Neural Networks

Recently, we developed a novel method for estimating human circadian phase with noninvasive ambulatory measurements combined with subject-independent multiple regression models and a curve-fitting approach. With this, we were able to estimate circadian phase under real-life conditions with low subject burden, i.e., without need of constant routine (CR) laboratory conditions, and without measuring standard circadian markers, such as core body temperature (CBT) or pineal hormone melatonin rhythms. The precision of ambulatory-derived estimated circadian phase was within an error of 12 ± 41 min (mean ± SD) in comparison to melatonin phase during a CR protocol. The physiological measures could be reduced to a triple combination: skin temperatures, irradiance in the blue spectral band of ambient light, and motion acceleration. Here, we present a nonlinear regression model approach based on artificial neural networks for a larger data set (25 healthy young males), including both the original data and additional data collected in the same protocol and using the same equipment. Throughout our validation study, subjects wore multichannel ambulatory monitoring devices and went about their daily routine for 1 wk. The devices collected a large number of physiological, behavioral, and environmental variables, including CBT, skin temperatures, cardiovascular and respiratory functions, movement/posture, ambient temperature, spectral composition and intensity of light perceived at eye level, and sleep logs. After the ambulatory phase, study volunteers underwent a 32-h CR protocol in the laboratory for measuring unmasked circadian phase (i.e., “midpoint” of the nighttime melatonin rhythm). To overcome the complex masking effects of many different confounding variables during ambulatory measurements, neural network–based nonlinear regression techniques were applied in combination with the cross-validation approach to subject-independent prediction of circadian phase. The most accurate estimate of circadian phase with a prediction error of −3 ± 23 min (mean ± SD) was achieved using only two types of the measured variables: skin temperatures and irradiance for ambient light in the blue spectral band. Compared to our previous linear multiple regression modeling approach, motion acceleration data can be excluded and prediction accuracy, nevertheless, improved. Neural network regression showed statistically significant improvement of variance of prediction error over traditional approaches in determining circadian phase based on single predictors (CBT, motion acceleration, or sleep logs), even though none of these variables was included as predictor. We, therefore, have identified two sets of noninvasive measures that, combined with the prediction model, can provide researchers and clinicians with a precise measure of internal time, in spite of the masking effects of daily behavior. This method, here validated in healthy young men, requires testing in a clinical or shiftwork population suffering from circadian sleep-wake disorders. (Author correspondence: vitaliy.kolodyazhniy@sbg.ac.at)

Intrinsic Circadian Period of Sighted Patients with Circadian Rhythm Sleep Disorder, Free-Running Type

Circadian rhythm sleep disorder, free-running type (FRT), is an intractable sleep disorder in which sleep and wake times progressively delay each day even in normal living environments. This disorder severely affects the social functioning of patients because of periodic nighttime insomnia, excessive daytime sleepiness, and a high rate of comorbid psychiatric disorders. Although abnormal regulation of the biological clock is suspected, the pathophysiology of FRT has yet to be elucidated. In this study, the endogenous circadian period, τ, of FRT patients with normal vision was compared with that of healthy individuals whose circadian rhythms are entrained to a 24-hour cycle. Six FRT patients and 17 healthy individuals (9 intermediate chronotypes and 8 evening chronotypes) were subjected to a 7-day, 28-hour sleep-wake schedule according to the forced desynchrony protocol. Phase shifts in melatonin rhythm were measured under constant routine conditions to calculate τ. In FRT patients, τ was significantly longer than in intermediate chronotypes, whereas in evening chronotypes, it ranged widely and was not significantly different from that in FRT patients. Moreover, τ of melatonin rhythm in FRT patients showed no significant correlation with τ of sleep-wake cycles measured before the study. The findings suggest that although a prolongation of τ may be involved in the onset mechanism of FRT, a prolonged τ is not the only factor involved. It appears that several factors including abnormal entrainment of circadian rhythms are involved in the onset of FRT in a multilayered manner.

The effect of extended wake on postural control in young adults

The sleep-wake cycle is a major determinant of locomotor activity in humans, and the neural and physiological processes necessary for optimum postural control may be impaired by an extension of the wake period into habitual sleep time. There is growing evidence for such a contribution from sleep-related factors, but great inconsistency in the methods used to assess this contribution, particularly in control for circadian phase position. Postural control was assessed at hourly intervals across 14h of extended wake in nine young adult participants. Force plate parameters of medio-lateral and anterior-posterior sway, centre of pressure (CoP) trace length, area, and velocity were assessed with eyes open and eyes closed over 3-min periods. A standard measure of psychomotor vigilance was assessed concurrently under constant routine conditions. After controlling for individual differences in circadian phase position, a significant effect of extended wake was found for anterior-posterior sway and for psychomotor vigilance. These data suggest that extended wake may increase the risk of a fall or other consequences of impaired postural control.

Challenging the sleep homeostat: Sleep in depression is not premature aging

The close relationship between major depression and sleep disturbances led to the hypothesis of a deficiency in homeostatic sleep pressure in depression (S-deficiency hypothesis). Many observed changes of sleep characteristics in depression are also present in healthy aging, leading to the premise that sleep in depression resembles premature aging. In this study, we aimed at quantifying the homeostatic sleep-wake regulation in young women with major depression and healthy young and older controls under high sleep pressure conditions. After an 8-h baseline night nine depressed women, eight healthy young, and eight healthy older women underwent a 40-h sustained wakefulness protocol followed by a recovery night under constant routine conditions. Polysomnographic recordings were carried out continuously. Sleep parameters as well as the time course of EEG slow-wave activity (SWA) (EEG spectra range: 0.75-4.5 Hz), as a marker of homeostatic sleep pressure, were analyzed during the recovery night. Young depressed women exhibited higher absolute mean SWA levels and a stronger response to sleep deprivation, particularly in frontal brain regions. In contrast, healthy older women exhibited not only attenuated SWA values compared to the other two groups, but also an absence of the frontal SWA predominance. Homeostatic sleep regulation and sleep architecture in young depressed women are not equal to premature aging. Moreover, our findings demonstrate that young moderately depressed women exhibit no deficiency in the sleep homeostatic process S as predicted by the S-deficiency hypothesis, but, rather, live on an elevated level of homeostatic sleep pressure.

Young Women With Major Depression Live on Higher Homeostatic Sleep Pressure Than Healthy Controls

There is mounting evidence for the involvement of the sleep-wake cycle and the circadian system in the pathogenesis of major depression. However, only a few studies so far focused on sleep and circadian rhythms under controlled experimental conditions. Thus, it remains unclear whether homeostatic sleep pressure or circadian rhythms, or both, are altered in depression. Here, the authors aimed at quantifying homeostatic and circadian sleep-wake regulatory mechanisms in young women suffering from major depressive disorder and healthy controls during a multiple nap paradigm under constant routine conditions. After an 8-h baseline night, 9 depressed women, 8 healthy young women, and 8 healthy older women underwent a 40-h multiple nap protocol (10 short sleep-wake cycles) followed by an 8-h recovery night. Polysomnographic recordings were done continuously, and subjective sleepiness was assessed. In order to measure circadian output, salivary melatonin samples were collected during scheduled wakefulness, and the circadian modulation of sleep spindles was analyzed with reference to the timing of melatonin secretion. Sleep parameters as well as non-rapid eye movement (NREM) sleep electroencephalographic (EEG) spectra were determined for collapsed left, central, and right frontal, central, parietal, and occipital derivations for the night and nap-sleep episodes in the frequency range .75–25 Hz. Young depressed women showed higher frontal EEG delta activity, as a marker of homeostatic sleep pressure, compared to healthy young and older women across both night sleep episodes together with significantly higher subjective sleepiness. Higher delta sleep EEG activity in the naps during the biological day were observed in young depressed women along with reduced nighttime melatonin secretion as compared to healthy young volunteers. The circadian modulation of sleep spindles between the biological night and day was virtually absent in healthy older women and partially impaired in young depressed women. These data provide strong evidence for higher homeostatic sleep pressure in young moderately depressed women, along with some indications for impairment of the strength of the endogenous circadian output signal involved in sleep-wake regulation. This finding may have important repercussions on the treatment of the illness as such that a selective suppression of EEG slow-wave activity could promote acute mood improvement. (Author correspondence: Christian.cajochen@upkbs.ch)

O-13 - Challenging the sleep homeostat in young depressed and healthy older women: sleep in depression is not premature aging

Major depression and sleep disturbances are closely related and often occur concomitantly. Many of the observed changes of sleep characteristics in depression are also present in healthy aging, which led to the premise that sleep in depression resembles premature aging. Here, we aimed at quantifying the homeostatic and circadian sleep-wake regulatory components in young women suffering from major depression disorder and healthy young and older control women during 40 hours of sustained wakefulness. After an 8-h baseline night 9 depressed women, 8 healthy young and 8 healthy older women underwent a 40-hour sustained wakefulness protocol followed by a recovery night under constant routine conditions. Polysomnographic recordings were carried out continuously. Sleep parameters as well as the time course of EEG slow-wave activity (SWA) (EEG spectra range: 0.75-4.5 Hz), as a marker of homeostatic sleep pressure, was analyzed during the recovery night. Young depressed women exhibited higher absolute mean SWA levels and a stronger response to sleep deprivation compared to healthy young and healthy older women, particularly in frontal brain regions. In contrast, healthy older women exhibited attenuated SWA values compared to the other two groups and an absence of the frontal predominance of mean SWA during the recovery night. Our data clearly show that homeostatic sleep regulation as well as sleep architecture in young depressed women is not equal to premature aging. Moreover, our findings demonstrate that young depressed women live on an elevated level of homeostatic sleep pressure.

Higher frontal EEG synchronization in young women with major depression: a marker for increased homeostatic sleep pressure?

Major depressive disorder (MDD) is often associated with disturbances in circadian and/or sleep-wake dependent processes, which both regulate daytime energy and sleepiness levels. Analysis of continuous electroencephalographic (EEG) recordings during 40 h of extended wakefulness under constant routine conditions. Artifact-free EEG samples derived from 12 locations were subjected to spectral analysis. Additionally, half-hourly ratings of subjective tension and sleepiness levels and salivary melatonin measurements were collected. Centre for Chronobiology, Psychiatric Hospitals of the University of Basel, Switzerland. Eight young healthy women and 8 young untreated women with MDD. N/A. MDD women exhibited higher frontal low-frequency (FLA) EEG activity (0.5-5.0 Hz) during extended wakefulness than controls, particularly during the night. Enhanced FLA was paralleled by higher levels of subjective sleepiness and tension. In MDD women, overall FLA levels correlated positively with depression scores. The timing of melatonin onset did not significantly differ between the two groups, but the nocturnal secretion of salivary melatonin was significantly attenuated in MDD women. Our data imply that young women with MDD live on a higher homeostatic sleep pressure level, as indexed by enhanced FLA during wakefulness. Its positive correlation with depression scores indicates a possible functional relationship. High FLA could reflect a use-dependent phenomenon in depression (enhanced cognitive rumination or tension) and/or an attenuated circadian arousal signal.

Cortical activation patterns herald successful dream recall after NREM and REM sleep

Dreaming pertains to both REM and NREM sleep. However, frequency and regional specific differences in EEG activity remains controversial. We investigated NREM and REM sleep EEG power density associated with and without dream recall in 17 young subjects during a 40-h multiple nap protocol under constant routine conditions. NREM sleep was associated with lower EEG power density for dream recall in the delta range, particularly in frontal derivations, and in the spindle range in centro-parietal derivations. REM sleep was associated with low frontal alpha activity and with high alpha and beta activity in occipital derivations. Our data indicate that specific EEG frequency- and topography changes underlie differences between dream recall and no recall after both NREM and REM sleep awakening. This dual NREM-REM sleep modulation holds strong implications for the mechanistic understanding of this complex ongoing cognitive process.

Estimation of Human Circadian Phase via a Multi-Channel Ambulatory Monitoring System and a Multiple Regression Model

Reliable detection of circadian phase in humans using noninvasive ambulatory measurements in real-life conditions is challenging and still an unsolved problem. The masking effects of everyday behavior and environmental input such as physical activity and light on the measured variables need to be considered critically. Here, we aimed at developing techniques for estimating circadian phase with the lowest subject burden possible, that is, without the need of constant routine (CR) laboratory conditions or without measuring the standard circadian markers, (rectal) core body temperature (CBT), and melatonin levels. In this validation study, subjects (N = 16) wore multi-channel ambulatory monitoring devices and went about their daily routine for 1 week. The devices measured a large number of physiological, behavioral, and environmental variables, including CBT, skin temperatures, cardiovascular and respiratory function, movement/posture, ambient temperature, and the spectral composition and intensity of light received at eye level. Sleep diaries were logged electronically. After the ambulatory phase, subjects underwent a 32-h CR procedure in the laboratory for measuring unmasked circadian phase based on the "midpoint" of the salivary melatonin profile. To overcome the complex masking effects of confounding variables during ambulatory measurements, multiple regression techniques were applied in combination with the cross-validation approach to subject-independent prediction of circadian phase. The most accurate estimate of circadian phase was achieved using skin temperatures, irradiance for ambient light in the blue spectral band, and motion acceleration as predictors with lags of up to 24 h. Multiple regression showed statistically significant improvement of variance of prediction error over the traditional approaches to determining circadian phase based on single predictors (motion acceleration or sleep log), although CBT was intentionally not included as the predictor. Compared to CBT alone, our method resulted in a 40% smaller range of prediction errors and a nonsignificant reduction of error variance. The proposed noninvasive measurement method could find applications in sleep medicine or in other domains where knowing the exact endogenous circadian phase is important (e.g., for the timing of light therapy).

Circadian rhythms in handwriting kinematics and legibility

The aim of the present study was to analyze the circadian rhythmicity in handwriting kinematics and legibility and to compare the performance between Dutch and German writers. Two subject groups underwent a 40 h sleep deprivation protocol under Constant Routine conditions either in Groningen (10 Dutch subjects) or in Berlin (9 German subjects). Both groups wrote every 3 h a test sentence of similar structure in their native language. Kinematic handwriting performance was assessed with a digitizing tablet and evaluated by writing speed, writing fluency, and script size. Writing speed (frequency of strokes and average velocity) revealed a clear circadian rhythm, with a parallel decline during night and a minimum around 3:00 h in the morning for both groups. Script size and movement fluency did not vary with time of day in neither group. Legibility of handwriting was evaluated by intra-individually ranking handwriting specimens of the 13 sessions by 10 German and 10 Dutch raters. Whereas legibility ratings of the German handwriting specimens deteriorated during night in parallel with slower writing speed, legibility of the Dutch handwriting deteriorated not until the next morning. In conclusion, the circadian rhythm of handwriting kinematics seems to be independent of script language at least among the two tested western countries. Moreover, handwriting legibility is also subject to a circadian rhythm which, however, seems to be influenced by variations in the assessment protocol.

Does the circadian modulation of dream recall modify with age?

The ultradian NREM-REM sleep cycle and the circadian modulation of REM sleep sum to generate dreaming. Here we investigated age-related changes in dream recall, number of dreams, and emotional domain characteristics of dreaming during both NREM and REM sleep. Analysis of dream recall and sleep EEG (NREM/REM sleep) during a 40-h multiple nap protocol (150 min of wakefulness and 75 min of sleep) under constant routine conditions. Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland. Seventeen young (20-31 years) and 15 older (57-74 years) healthy volunteers N/A. Dream recall and number of dreams varied significantly across the circadian cycle and between age groups, with older subjects exhibiting fewer dreams (P < 0.05), particularly after naps scheduled during the biological day, closely associated with the circadian rhythm of REM sleep. No significant age differences were observed for the emotional domain of dream content. Since aging was associated with attenuated amplitude in the circadian modulation of REM sleep, our data suggest that the age-related decrease in dream recall can result from an attenuated circadian modulation of REM sleep.

Subjective Well-Being Is Modulated by Circadian Phase, Sleep Pressure, Age, and Gender

Subjective well-being largely depends on mood, which shows circadian rhythmicity and can be linked to rhythms in many physiological circadian markers, such as melatonin and cortisol. In healthy young volunteers mood is influenced by an interaction of circadian phase and the duration of time awake. The authors analyzed this interaction under differential sleep pressure conditions to investigate age and gender effects on subjective well-being. Sixteen healthy young (8 women, 8 men; 20-35 years) and 16 older volunteers (8 women, 8 men; 55-75 years) underwent a 40-h sleep deprivation (high sleep pressure) and a 40-h nap protocol (low sleep pressure) in a balanced crossover design under constant routine conditions. Mood, tension, and physical comfort were assessed by visual analogue scales during scheduled wakefulness, and their average formed a composite score of well-being. Significant variations in well-being were determined by the factors "age," "sleep pressure," and "circadian phase." Well-being was generally worse under high than low sleep pressure. Older volunteers felt significantly worse than the young under both experimental conditions. Significant interactions were found between "sleep pressure" and "age," and between "sleep pressure" and "gender." This indicated that older volunteers and women responded with a greater impairment in well-being under high compared with low sleep pressure. The time course of well-being displayed a significant circadian modulation, particularly in women under high sleep pressure conditions. The results demonstrate age- and/or gender-related modifications of well-being related to sleep deprivation and circadian phase and thus point to specific biological components of mood vulnerability.

Circadian rhythm in handwriting

The aim of the present study was to determine whether the motor process of handwriting is influenced by a circadian rhythm. Nine healthy young male subjects underwent a 40-h sleep deprivation protocol under constant routine conditions. Starting at 09:00 hours, subjects performed every 3 h two handwriting tasks of different complexity. Handwriting performance was evaluated by writing speed, writing fluency and script size. The frequency of handwriting, as a measure of movement speed, revealed a circadian rhythm, validated by harmonic regression, with a slowing at the time of the onset of melatonin secretion (22:17 hours) and a trough in the very early morning at around 03:30 hours. In the temporal variability of handwriting an effect of task complexity was suggested in the direction of circadian variations in parallel with speed only for the sentence. Despite deficits of speed and temporal variability, writing fluency did not change significantly across sessions indicating that the basic automation of handwriting was preserved at any time. On the second day, daytime levels of the kinematics of handwriting did not reflect impaired performance after sleep deprivation. Our results show for the first time a clear circadian rhythm for the production of handwriting.

Impact of age, sleep pressure and circadian phase on time-of-day estimates

Orientation and self-location within the temporal fabric of the environment involves multiple organismic systems. While temporal self-location on the physiological level has been known for some time to be based on a ‘biological clock’ located within the hypothalamus, the mechanisms that participate in temporal position finding on the cognitive level are not yet fully understood. In order to probe the mechanisms that underlie this faculty, verbal estimates on time-of-day were collected at 3.75-h intervals from 16 young (7 males, 8 females; 20–31 years) and 16 older (8 males, 8 females; 57–74 years) subjects in a balanced crossover design during 40-h epochs of prolonged wakefulness and 40-h epochs of sleep satiation spent under constant routine conditions. An overestimation of clock time during prolonged wakefulness was found in both age-groups, with significantly larger errors for the older group (young: 0.5 ± 0.2 h; older: 1.5 ± 0.2 h, p < 0.05). In both age-groups, estimation errors ran roughly parallel to the time course of core body temperature. However a significant interaction between time-of-day and age-group was observed (rANOVA, p < 0.05): younger subjects exhibited similar estimation errors as the older subjects after 16 h of prior wakefulness, whereas the latter did not manifest decrements under high sleep pressure. Data collected under conditions of sleep satiation also displayed a diurnal oscillation in estimation errors and a general overestimation (young: 0.8 ± 0.2 h; older: 1.3 ± 0.3 h, p < 0.05). Here however, the age-groups did not differ significantly nor was there an interactive effect between time-of-day and age-group. The effects of age, duration of wake time and circadian phase on temporal position finding are in line with predictions based on the idea that awareness about current position in time is derived from interval timing processes.

Circadian Variations in the Kinematics of Handwriting and Grip Strength

The present study determined whether the motor process of handwriting is influenced by a circadian rhythm during writing tasks of high everyday relevance and analyzed the relationship to the circadian rhythm of grip strength. Ten healthy young male subjects underwent a 40 h sleep‐deprivation protocol under constant routine conditions. Starting at 09:00 h, subjects performed three handwriting tasks of increasing perceptual‐motor complexity (writing a sentence, writing one's signature, and copying a text for 3 min) and assessed grip strength of both hands every 3 h. Handwriting performance was analyzed by writing speed, writing fluency, script size, break times, and pen pressure. The handwriting tasks revealed a coincident circadian rhythm for the frequency of handwriting as a measure of movement speed, with slowest writing speed at 03:16 h. A weak effect of task complexity was evident for the non‐writing episodes: while copying a text, break times were influenced by a circadian rhythm, whereas during sentence writing, the non‐writing episodes remained constant. The circadian rhythm of grip strength paralleled the time course of motivation ratings, with least motivation and weakest grip strength around 06:00 h concurrently for both hands. The rate of force production also displayed circadian rhythmicity and sharply decreased with the onset of melatonin secretion. Neither grip strength nor the kinematics of handwriting was influenced by sleep deprivation; only the level of the force rate was decreased the second day. The results show a clear circadian rhythm in the speed of handwriting and grip strength.

BLUE LIGHT Exposure Reduces Objective Measures of Sleepiness during Prolonged Nighttime Performance Testing

This study examined the effects of nocturnal exposure to dim, narrowband blue light (460 nm, ∼1 lux, 2 µW/cm2), compared to dim broad spectrum (white) ambient light (∼0.2 lux, 0.5 µW/cm2), on subjective and objective indices of sleepiness during prolonged nighttime performance testing. Participants were also exposed to a red light (640 nm, ∼1 lux, 0.7µW/cm2) placebo condition. Outcome measures were driving simulator and psychomotor vigilance task (PVT) performance, subjective sleepiness, salivary melatonin, and electroencephalographic (EEG) activity. The study had a repeated-measures design, with three counterbalanced light conditions and a four-week washout period between each condition. Participants (n = 8) maintained a regular sleep-wake schedule for 14 days prior to the ∼14 h laboratory study, which consisted of habituation to light conditions followed by neurobehavioral performance testing from 21:00 to 08:30 h under modified constant-routine conditions. A neurobehavioral test battery (2.5 h) was presented four times between 21:00 and 08:30 h, with a 30 min break between each. From 23:30 to 05:30 h, participants were exposed to blue or red light, or remained in ambient conditions. Compared to ambient light exposure, blue light exposure suppressed EEG slow wave delta (1.0–4.5 Hz) and theta (4.5–8 Hz) activity and reduced the incidence of slow eye movements. PVT reaction times were significantly faster in the blue light condition, but driving simulator measures, subjective sleepiness, and salivary melatonin levels were not significantly affected by blue light. Red light exposure, as compared to ambient light exposure, reduced the incidence of slow eye movements. The results demonstrate that low-intensity, blue light exposure can promote alertness, as measured by some of the objective indices used in this study, during prolonged nighttime performance testing. Low intensity, blue light exposure has the potential to be applied to situations where it is desirable to increase alertness but not practical or appropriate to use bright light, such as certain occupational settings.

The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults

Inflammatory cytokines are released in response to stress, tissue damage, and infection. Acutely, this response is adaptive; however, chronic elevation of inflammatory proteins can contribute to health problems including cardiovascular, endocrine, mood, and sleep disorders. Few studies have examined how sleep deprivation acutely affects inflammatory markers, which was the aim of the current study. Nineteen healthy men and women aged 28.05 ± 8.56 (mean ± SD) were totally sleep deprived for 40 h under constant routine conditions. Pro-inflammatory markers: intracellular adhesion molecule-1 (ICAM-1), E-selectin, vascular adhesion molecule-1 (VCAM-1), c-reactive protein (CRP), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra) were assayed in plasma. Daytime levels during baseline (hours 1–15 of scheduled wakefulness) were compared to daytime levels during sleep deprivation (hours 25–39 of scheduled wakefulness), thus controlling for circadian phase within an individual. Repeated measures ANOVA with planned comparisons showed that 40 h of total sleep deprivation induced a significant increase in E-selectin, ICAM-1, IL-1β, and IL-1ra, a significant decrease in CRP and IL-6, and no significant change in VCAM-1. Alterations in circulating levels of pro- and anti-inflammatory cytokines and cell adhesion molecules during sleep deprivation were consistent with both increased and decreased inflammation. These findings suggest that one night of sleep loss triggers a stress response that includes stimulation of both pro- and anti-inflammatory proteins in the healthy young subjects tested under our experimental conditions.

Circadian variation in endothelial function is attenuated in postmenopausal women

Objective The present study was undertaken to investigate the possible existence of an endogenously generated circadian rhythm in endothelial function in women and whether this rhythm is altered after the menopause. Methods Healthy non smoking women (11 pre-menopausal and 13 postmenopausal women) were studied during a 22 h period under constant routine conditions; endothelium-dependent (flow-mediated dilation (%FMD)) and -independent (glyceryl-trintrate (GTN)-mediated) function was assessed every 2 and 4 h, respectively, by high-resolution ultrasound of the brachial artery. Results %FMD and %GTN was significantly higher in pre-menopausal women (9.9 ± 1.0%FMD (mean ± S.E.M.); 18.2 ± 1.8%GTN; P < 0.01) compared with postmenopausal women (6.5 ± 0.5%FMD; 11.5 ± 1.6%GTN). A significant day–night variation in %FMD was observed pre-menopausal women (day 9.2 ± 0.8%; night 10.4 ± 1%; P < 0.05) with an attenuated rhythm in postmenopausal women (day 6.8 ± 0.6%; night 6.0 ± 0.4%). Conclusions The findings show a circadian rhythm in %FMD in pre-menopausal women, which disappears after the menopause. The reduction in %FMD and an absence of a day–night variation in %FMD in postmenopausal women may have important implications for the incidence of coronary heart disease in women after the menopause.

Sleep loss‐related decrements in planning performance in healthy elderly depend on task difficulty

Prefrontal cortex (PFC)-related functions are particularly sensitive to sleep loss. However, their repeated examination is intricate because of methodological constraints such as practice effects and loss of novelty. We investigated to what extent the circadian timing system and the sleep homeostat influence PFC-related performance in differently difficult versions of a single task. Parallel versions of a planning task combined with a control group investigation were used to control for practice effects. Thirteen healthy volunteers (five women and eight men, range 57-74 years) completed a 40-h sleep deprivation (SD) and a 40-h multiple nap protocol (NAP) under constant routine conditions. Each participant performed 11 easy and 11 difficult task versions under either SD or NAP conditions. The cognitive and motor components of performance could be distinguished and analysed separately. Only by thoroughly controlling for superimposed secondary factors such as practice or sequence effects, could a significant influence of circadian timing and sleep pressure be clearly detected in planning performance in the more difficult, but not easier maze tasks. These results indicate that sleep loss-related decrements in planning performance depend on difficulty level, and that apparently insensitive tasks can turn out to be sensitive to sleep loss and circadian variation.

Age-Related Changes in the Circadian Modulation of Sleep-Spindle Frequency During Nap Sleep

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. A 40-hour multiple-nap paradigm under constant-routine conditions Chronobiology Laboratory, University Psychiatric Hospitals, Basel, Switzerland Seventeen younger (20-31 years) and 15 older (57-74 years) volunteers. N/A. 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. 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.