Estimates of the Daily Phase and Amplitude of the Endogenous Component of the Circadian Rhythm of Core Temperature in Sedentary Humans Living Nychthemerally

Fifteen healthy female subjects were studied for eight days while living conventionally. Subjects were free to choose the ways they spent their time within a framework of regular times of retiring and rising; in practice, much of the waking time was spent in sedentary activities. Nine of the subjects were aware of the natural light-dark cycle, this approximating to a 12:12 L:D schedule at the time of year when the study took place. Before the study, subjects were assessed for their degree of "morningness" by questionnaire; throughout the study, they wore a rectal probe, and an activity meter on their non-dominant wrist. The timing (phase) and amplitude of the circadian rectal temperature rhythm were assessed on each day by cosinor analysis as well as by a me thod based on visual inspection of the data. These two parameters were also assessed after the temperature data for each day had been "purified" by a number of methods. From these results it was possible to investigate the effect of purification upon the amplitude of the circadian rhythm of temperature. Also, the day-by-day variability of phase, and the relationship between morningness and phase, were compared using these methods of phase estimation, and using cross-correlation between data sets from adjacent days; in all cases, raw and purified temperature data were used. There was a significantly greater amount of daily variation in phase using purified rather than raw data sets, and this difference was present with all methods of purification as well as with all methods for estimating phase. Purifi cation decreased the amplitude of the circadian temperature rhythm by about 30%. Finally, there was a significant correlation between the morningness score of the subjects and the phase of the circadian temperature rhythm, the phase becoming earlier with increasing morningness; when this relationship was re-examined using purified data, it became more marked. These results reflect the masking effects exerted upon raw temperature data by lifestyle. The extent to which the purification methods enable the endogenous component of a circadian rhythm – and, by implication, the output of the endogenous circadian oscillator – to be estimated in subjects living normally is addressed.     

The Shape of the Endogenous Circadian Rhythm of Rectal Temperature in Humans

Fourteen healthy subjects have been studied in an isolation unit while living on a 30h “day” (20h awake, 10h asleep) for 14 (solar) days but while aware of real time. Waking activities were sedentary and included reading, watching television, and so forth. Throughout, regular recordings of rectal temperature were made, and in a subgroup of 6 subjects, activity was measured by a wrist accelerometer. Temperature data have been subjected to cosinor analysis after “purification,” a method that enables the endogenous (clock-driven) and exogenous (activity-driven) components of the circadian rhythm to be assessed. Moreover, the protocol enables effects due to the circadian rhythm and time-since-waking to be separated. Results showed that activity was slightly affected by the endogenous temperature rhythm. Also, the masking effects on body temperature exerted by the exogenous factors appeared to be less than average in the hours before and just after the peak of the endogenous temperature rhythm. This has the effect of producing a temperature plateau rather than a peak during the daytime. The implications of this for mental performance and sleep initiation are discussed. (Chronobiology International, 13(4), 261-271, 1996)     

Absence of Seasonal Variation in the Phase of the Endogenous Circadian Rhythm in Humans

Humans may be subject to seasonal variations, as evidenced by the existence of seasonal affective disorder (SAD) and midwinter insomnia. However, some recent studies have shown that the seasonal variation in the phase of the circadian rhythm is relatively weak in healthy humans. In the present study, evidence is found that there is no seasonal variation in the phase of the endogenous circadian rhythm at all. Body temperature, cortisol excretion, and subjective alertness of six subjects recorded under constant routine conditions showed no systematic seasonal variation in circadian phases. This finding indicates that secondary zeitgebers blocked or counterbalanced the seasonal variation in the entrainment effect of the natural photo-period. The human being may live in an environment in which the photoperiod has lost its status of primary zeitgeber. (Chronobiology International, 15(6), 623-632, 1998)     

A Mathematical Method for Studying the Endogenous Component of the Circadian Temperature Rhythm and the Effect of Aging

A mathematical model was developed in order to study the endogenous component of the circadian rhythm in body temperature. The model describes the fluctuations in body temperature as a function of a cosine-shaped endogenous rhythm plus an exogenous component which is linearly correlated with the time spent in active wakefulness. The model was evaluated in 4 young and 4 old rats. In 7 out of 8 rats there was a significant lack of fit when the traditional cosinor method was used, as compared with only 1 out of 8 when using our model. In all 8 rats the regression was highly significant and also useful as defined by the ? m criterion. The results from the model were in agreement with literature regarding constant routine studies in humans. The mean amplitude of the endogenous rhythm was 0.24°C in young rats and 0.19°C in old rats, whereas the amplitudes of the overt rhythm were 0.38 and 0.26°C, respectively. The age-related differences in the amplitude of the overt circadian temperature rhythm could to a large extent be attributed to age-related differences in activity-induced heat production. Finally, the acrophase of the endogenous rhythm occurred 18.7 minutes later than that of the overt rhythm. If applicable to human, the proposed method may form a valuable extension to existing constant routine protocols for studying the endogenous circadian rhythm in body temperature.     

The Variability in Circadian Phase and Amplitude Estimates Derived from Sequential Constant Routines

Both the constant routine (CR) and the dim light melatonin onset have been suggested as reliable methods to determine circadian phase from a single circadian cycle. However, both techniques lack published studies quantifying the intercycle variability in their phase resolution. To address this question eight healthy male subjects participated in two CRs, 7 days apart. Circadian phase was determined using 3-min samples of core body temperature and two hourly urinary sulphatoxy melatonin excretion rates. Phase and amplitude were estimated using simple (24 h) and complex (24 + 12 h) cosinor models of temperature data and the onset, offset, and a distance-weighted-least-squares (DWLS) fitted acrophase for the melatonin metabolite. The variability in phase estimates was measured using the mean absolute difference between successive CRs. Using the simple 24 h model of temperature data, the mean absolute phase difference was 51 min (SD = 35 min). Using the complex model, the mean absolute phase difference was 62 min (SD = 35 min). Using the DWLS fitted acrophase for the melatonin metabolite, the mean absolute phase difference between CR1 and CR2 was 40 min (SD = 26 min). The results indicate that for CRs a week apart, the mean absolute difference in an individual's phase estimate can vary by 40-60 min depending on the choice of dependent measure and analytic technique. In contrast to the intraindi-vidual variability, the group results showed considerably less variability. The mean algebraic difference between CRs, using temperature- or melatonin-derived estimates, was less than 5 min, and well within the range of normal measurement error.     

Phase Shifting the ERG Amplitude Circadian Rhythm of Juvenile Crayfish by Caudal Monochromatic Illumination

The objective of the present work was to determine the physiological mechanisms underlying the synchronization of the ERG amplitude rhythm. Chronic ERG recordings were obtained from juvenile instars of crayfish. Changes on the ERG amplitude rhythm produced when 30 min blue light illuminated the telson were determined. The PRC obtained with these data showed advances in the early subjective night and delays in the late subjective night. These phase shiftings resemble the features of curves obtained by dark pulses in other species. The relation of this curve with PRCs generated in the crayfish and other animals species are discussed.     

Phase Shifting the ERG Amplitude Circadian Rhythm of Juvenile Crayfish by Caudal Monochromatic Illumination

The objective of the present work was to determine the physiological mechanisms underlying the synchronization of the ERG amplitude rhythm. Chronic ERG recordings were obtained from juvenile instars of crayfish. Changes on the ERG amplitude rhythm produced when 30 min blue light illuminated the telson were determined. The PRC obtained with these data showed advances in the early subjective night and delays in the late subjective night. These phase shiftings resemble the features of curves obtained by dark pulses in other species. The relation of this curve with PRCs generated in the crayfish and other animals species are discussed.     

The Circadian Body Temperature Rhythm in the Elderly: Effect of Single Daily Melatonin Dosing

The present study is part of a more extensive investigation dedicated to the study and treatment of age‐dependent changes/disturbances in the circadian system in humans. It was performed in the Tyumen Elderly Veteran House and included 97 subjects of both genders, ranging from 63 to 91 yrs of age. They lived a self‐chosen sleep‐wake regimen to suit their personal convenience. The experiment lasted 3 wks. After 1 control week, part of the group (n=63) received 1.5 mg melatonin (Melaxen?) daily at 22:30 h for 2 wks. The other 34 subjects were given placebo. Axillary temperature was measured using calibrated mercury thermometers at 03:00, 08:00, 11:00, 14:00, 17:00, and 23:00 h each of the first and third week. Specially trained personnel took the measurements, avoiding disturbing the sleep of the subjects. To evaluate age‐dependent changes, data obtained under similar conditions on 58 young adults (both genders, 17 to 39 yrs of age) were used. Rhythm characteristics were estimated by means of cosinor analyses, and intra‐ and inter‐individual variability by analysis of variance (ANOVA). In both age groups, the body temperature underwent daily changes. The MESOR (36.38±0.19°C vs. 36.17±0.21°C) and circadian amplitude (0.33±0.01°C vs. 0.26±0.01°C) were slightly decreased in the elderly compared to the young adult subjects (p<0.001). The mean circadian acrophase was similar in both age groups (17.19±1.66 vs. 16.93±3.08 h). However, the inter‐individual differences were higher in the older group, with individual values varying between 10:00 and 23:00 h. It was mainly this phase variability that caused a decrease in the inter‐daily rhythm stability and lower group amplitude. With melatonin treatment, the MESOR was lower by 0.1°C and the amplitude increased to 0.34±0.01°C, a similar value to that found in young adults. This was probably due to the increase of the inter‐daily rhythm stability. The mean acrophase did not change (16.93 vs. 16.75 h), although the inter‐individual variability decreased considerably. The corresponding standard deviations (SD) of the group acrophases were 3.08 and 1.51 h (p<0.01). A highly significant correlation between the acrophase before treatment and the phase change under melatonin treatment indicates that this is due to a synchronizing effect of melatonin. Apart from the difference in MESOR, the body temperature rhythm in the elderly subjects undergoing melatonin treatment was not significantly different from that of young adults. The data clearly show that age‐dependent changes mainly concern rhythm stability and synchronization with the 24 h day. A single daily melatonin dose stabilizes/synchronizes the body temperature rhythm, most probably via hypothermic and sleep‐improving effects.     

The Circadian Rhythm of Core Temperature: Origin and some Implications for Exercise Performance

This review first examines reliable and convenient ways of measuring core temperature for studying the circadian rhythm, concluding that measurements of rectal and gut temperature fulfil these requirements, but that insulated axilla temperature does not. The origin of the circadian rhythm of core temperature is mainly due to circadian changes in the rate of loss of heat through the extremities, mediated by vasodilatation of the cutaneous vasculature. Difficulties arise when the rhythm of core temperature is used as a marker of the body clock, since it is also affected by the sleep‐wake cycle. This masking effect can be overcome directly by constant routines and indirectly by “purification” methods, several of which are described. Evidence supports the value of purification methods to act as a substitute when constant routines cannot be performed. Since many of the mechanisms that rise to the circadian rhythm of core temperature are the same as those that occur during thermoregulation in exercise, there is an interaction between the two. This interaction is manifest in the initial response to spontaneous activity and to mild exercise, body temperature rising more quickly and thermoregulatory reflexes being recruited less quickly around the trough and rising phase of the resting temperature rhythm, in comparison with the peak and falling phase. There are also implications for athletes, who need to exercise maximally and with minimal risk of muscle injury or heat exhaustion in a variety of ambient temperatures and at different times of the day. Understanding the circadian rhythm of core temperature may reduce potential hazards due to the time of day when exercise is performed.     

A psychometric assessment of the Circadian Amplitude and Phase Scale

The Circadian Amplitude and Phase Scale (CAPS) is a new self-report tool that aims to assess amplitude and phase. The CAPS consists of three factors made up of 38 items. Amplitude is posited to be assessed via two of these factors: time awareness (TA) and/or strength of preference (SOP). The remaining factor, phase, is assessed via the existing Preferences Scale (PS). Given there is no published research using this measure, the authors undertook two studies to examine its psychometric properties and construct validity. In a sample of 351 North American students, the authors identified a three-factor 34-item model using principal components analysis. The components explained 39% of the variance, and scale reliability ranged from 0.73 (SOP) to 0.88 (PS). The correlations between the components were small, suggesting they are each assessing different constructs. Thus, it is unlikely TA and SOP may both be indicators of amplitude. The distributions for each scale were divided into two groups (≤ 25th and ≥ 75th percentiles), and these groups were used to assess construct validity using alertness ratings by time-of-day. The results from a multivariate general linear model indicated a significant difference (p?相似文献   

The Effects of Thoracic and Cervical Spinal Cord Lesions on the Circadian Rhythm of Core Body Temperature

Individuals with a spinal cord injury (SCI) have compromised afferent and efferent information below the lesion. Intact afferent information regarding skin temperature and the ability to regulate skin blood flow lead to an altered heat balance, which may impact the circadian variation in core body temperature (Tcore) and sleep-wake cycle. The authors assessed the circadian variation of Tcore in SCI individuals and able-bodied controls matched for the timing of the sleep-wake cycle. The authors examined subjects who had a high (cervical) or a low (thoracic) lesion. Intestinal Tcore (telemetry system) and physical activity (ambulatory activity monitor) levels were measured continuously and simultaneously in 8 tetraplegics, 7 paraplegics, and 8 able-bodied controls during one 24-h period of “normal” living. The regression slope between activity and Tcore was also calculated for each 2-h bin. Circadian rhythm parameters were estimated with partial Fourier time-series analysis, and groups were compared with general linear models, adjusted for the influence of individual wake-time. The (mean?±?SD) dominant period length for controls, paraplegics, and tetraplegics were 24.4?±?5.4?h, 22.5?±?5.0?h, and 16.5?±?5.1?h, respectively (p?=?.02). A significantly more pronounced 8-h harmonic was found for the variation in Tcore of SCI individuals (p = .05). Tetraplegics showed the highest nocturnal mean Tcore (p = .005), a 5-h phase-advanced circadian trough time (p = .04), and more variable relationships between physical activity and Tcore (p = .03). Taken together, tetraplegics demonstrate a pronounced disturbance of the circadian variation of Tcore, whereas the variation of Tcore in paraplegics was comparable to able-bodied controls. (Author correspondence: D.Thijssen@fysiol.umcn.nl)     

The Circadian Rhythm of Body Temperature of the Horse

Rectal temperature of 10 female adult horses was recorded every 2 h for 10 consecutive days under a natural winter photoperiod (9 h of light and 15 h of darkness per day). A robust daily rhythm of body temperature was observed in all animals. The rhythm had a mean level of 38.3°C and a range of excursion of 1.0°C. Temperature started its daily ascent at dawn each day and reached a maximum 14 hours later. Body temperature of 5 of the horses was studied for 10 more days under constant illumination. The rhythm persisted under this condition, although with a slightly longer period of 24.2 h, which confirms the endogenous nature of the rhythm. Despite the fact that the body size of the horse is several orders of magnitude greater than that of rodents, the various parameters of the body temperature rhythm of the horse are similar to those of several species of rodents previously studied.     

The Circadian Rhythm of Body Temperature of the Horse

Rectal temperature of 10 female adult horses was recorded every 2 h for 10 consecutive days under a natural winter photoperiod (9 h of light and 15 h of darkness per day). A robust daily rhythm of body temperature was observed in all animals. The rhythm had a mean level of 38.3°C and a range of excursion of 1.0°C. Temperature started its daily ascent at dawn each day and reached a maximum 14 hours later. Body temperature of 5 of the horses was studied for 10 more days under constant illumination. The rhythm persisted under this condition, although with a slightly longer period of 24.2 h, which confirms the endogenous nature of the rhythm. Despite the fact that the body size of the horse is several orders of magnitude greater than that of rodents, the various parameters of the body temperature rhythm of the horse are similar to those of several species of rodents previously studied.     

The Effect of Activity on the Waking Temperature Rhythm in Humans

Nine healthy female subjects were studied when exposed to the natural light-dark cycle, but living for 17 “days” on a 27h day (9h sleep, 18h wake). Since the circadian endogenous oscillator cannot entrain to this imposed period, forced desynchronization between the sleep/activity cycle and the endogenous circadian temperature rhythm took place. This enabled the effects of activity on core temperature to be assessed at different endogenous circadian phases and at different stages of the sleep/activity cycle. Rectal temperature was measured at 6-minute intervals, and the activity of the nondominant wrist was summed at 1-minute intervals. Each waking span was divided into overlapping 3h sections, and each section was submitted to linear regression analysis between the rectal temperatures and the total activity in the previous 30 minutes. From this analysis were obtained the gradient (of the change in rectal temperature produced by a unit change in activity) and the intercept (the rectal temperature predicted when activity was zero). The gradients were subjected to a two-factor analysis of variance (ANOVA) (circadian phase/ time awake). There was no significant effect of time awake, but circadian phase was highly significant statistically. Post hoc tests (Newman-Keuls) indicated that gradients around the temperature peak were significantly less than those around its trough. The intercepts formed a sinusoid that, for the group, showed a mesor (±SE) of 36.97 (±0.12) and amplitude (95% confidence interval) of 0.22°C (0.12°C, 0.32°C). We conclude that this is a further method for removing masking effects from circadian temperature rhythm data in order to assess its endogenous component, a method that can be used when subjects are able to live normally. We suggest also that the decreased effect of activity on temperature when the endogenous circadian rhythm and activity are at their peak will reduce the possibility of hyperthermia.     

Evening Alcohol Consumption Alters the Circadian Rhythm of Body Temperature

To the Editor: Recordings of body temperature rhythms are used as a marker of the circadian system in many fields of study, including shift work, jet lag, affective disorders, gerontology, and sleep disorders. In our studies of circadian rhythms, we routinely prohibit subjects from drinking alcohol because of findings published in 1933 (1). That study found that after alcohol consumption the nocturnal temperature minimum during sleep occurred earlier, and was higher, than on control nights. In the years since that report, there have been no other studies of how alcohol changes the temperature waveform during sleep, despite other studies of the dose- and time-dependent effects of ethanol in humans (2). We decided to investigate whether the results of the 1933 report would generalize to other subjects and to women.     

Circadian Rhythm of Temperature Preference and Its Neural Control in Drosophila

1. Download : Download high-res image (232KB)
2. Download : Download full-size image

Highlights? We identify a novel circadian behavior in flies, temperature preference rhythm (TPR) ? Drosophila TPR follows a similar pattern as body temperature rhythm in humans ? Drosophila TPR is regulated independently from circadian locomotor activity ? TPR is controlled by a newly identified DN2-based pacemaker circuit in the brain     

Light Synchronization of an Endogenous Circadian Rhythm of Cell Division in Tetrahymena*

SYNOPSIS. Synchronization of cell division in axenic cultures of the free-living ciliated eukaryote Tetrahymena pyriformis (W) may be achieved equally as well by a sudden increase in irradiance, DD→LL (switch-up), or by a sudden decrease in irradiance, LL→DD (switch-down), provided that the irradiance transition occurs after a critical time in the late ultradian exponential growth phase. Circadian division indices (～24 hrs) are associated with infradian generation times (GT>>24 hrs).     

Design and Analysis of Temperature Preference Behavior and its Circadian Rhythm in Drosophila

The circadian clock regulates many aspects of life, including sleep, locomotor activity, and body temperature (BTR) rhythms^1,2. We recently identified a novel Drosophila circadian output, called the temperature preference rhythm (TPR), in which the preferred temperature in flies rises during the day and falls during the night ³. Surprisingly, the TPR and locomotor activity are controlled through distinct circadian neurons³. Drosophila locomotor activity is a well known circadian behavioral output and has provided strong contributions to the discovery of many conserved mammalian circadian clock genes and mechanisms⁴. Therefore, understanding TPR will lead to the identification of hitherto unknown molecular and cellular circadian mechanisms. Here, we describe how to perform and analyze the TPR assay. This technique not only allows for dissecting the molecular and neural mechanisms of TPR, but also provides new insights into the fundamental mechanisms of the brain functions that integrate different environmental signals and regulate animal behaviors. Furthermore, our recently published data suggest that the fly TPR shares features with the mammalian BTR³. Drosophila are ectotherms, in which the body temperature is typically behaviorally regulated. Therefore, TPR is a strategy used to generate a rhythmic body temperature in these flies^5-8. We believe that further exploration of Drosophila TPR will facilitate the characterization of the mechanisms underlying body temperature control in animals.     

The use of Constant Routines in Unmasking the Endogenous Component of Human Circadian Rhythms

A major problem in the study of the internal clock(s) that drives human circadian rhythms is that due to the effect produced by rhythmicity of habits and external influences ('masking'). A particularly potent factor in this respect is the sleep-wake cycle. It is anomalous that, even though this masking influence is widely accepted, most studies of circadian rhythmicity have been performed in the presence of such interferences.

A protocol is described, the constant routine, by which these exogenous influences can be minimized, thereby enabling a closer scrutiny of the internal clock(s) to be made. An account is given of the different circumstances in which the constant routines have been used together with the results derived from such studies. Briefly, they indicate that nychthemeral studies can give misleading information about the rate of adjustment of the internal clock to various manipulations, e.g. time-zone transition, shift work.

In addition, future studies making use of constant routines are described, in particular those which might enable the presence of more than one internal clock to be established.     

The use of Constant Routines in Unmasking the Endogenous Component of Human Circadian Rhythms

A major problem in the study of the internal clock(s) that drives human circadian rhythms is that due to the effect produced by rhythmicity of habits and external influences (‘masking’). A particularly potent factor in this respect is the sleep-wake cycle. It is anomalous that, even though this masking influence is widely accepted, most studies of circadian rhythmicity have been performed in the presence of such interferences.

A protocol is described, the constant routine, by which these exogenous influences can be minimized, thereby enabling a closer scrutiny of the internal clock(s) to be made. An account is given of the different circumstances in which the constant routines have been used together with the results derived from such studies. Briefly, they indicate that nychthemeral studies can give misleading information about the rate of adjustment of the internal clock to various manipulations, e.g. time-zone transition, shift work.

In addition, future studies making use of constant routines are described, in particular those which might enable the presence of more than one internal clock to be established.