Neurobiology of Sleep and Circadian Rhythms最新文献

Objectives

To investigate the acute benefits of breaking up prolonged sitting with light-intensity physical activity on (i) glucose metabolism under conditions of sleep restriction, and (ii) cognitive deficits associated with sleep restriction.

Methods

This counterbalanced, crossover trial consisted of two five-day (5 night) experimental conditions separated by a two-week washout period. On the first night, participants were given a 9-h sleep opportunity to allow the collection of steady-state baseline measures the following day. This was followed by three consecutive nights of sleep restriction (5-h sleep opportunity). In the sitting condition (SIT), participants remained seated between 1000 and 1800 h. In the physical activity condition (ACT), participants completed 3-min bouts of light-intensity walking every 30 min on a motorised treadmill between 1000 and 1800 h. At all other times, in both conditions, participants remained seated, except when walking to the dining room or to use the bathroom (max distance = 32 m). Six physically inactive, healthy males were randomised to one of two trial orders, 1) SIT then ACT, or 2) ACT then SIT. Continuous measures of interstitial glucose were measured at 5-min intervals. A cognitive and subjective test battery was administered every two hours during wake periods. Analyses were conducted using a series of linear mixed-effect ANOVAs.

Results

No differences in interstitial glucose concentration or cognitive performance were observed between the SIT condition and the ACT condition. Participants reported higher levels of sleepiness, and felt less alert in the SIT condition compared with the ACT condition.

Conclusions

There were no observable benefits of breaking up prolonged sitting on glucose metabolism under conditions of sleep restriction. These findings have implications for behaviour change interventions. Future studies will need to include larger, less homogenous study populations and appropriate control conditions (i.e., 8–9 h sleep opportunities).

Daytime light exposure has been reported to impact or have no influence on energy metabolism in humans. Further, whether inter-individual differences in wake, sleep, 24 h energy expenditure, and RQ during circadian entrainment and circadian misalignment are stable across repeated 24 h assessments is largely unknown. We present data from two studies: Study 1 of 15 participants (7 females) exposed to three light exposure conditions: continuous typical room ~100 lx warm white light, continuous ~750 lx warm white light, and alternating hourly ~750 lx warm white and blue-enriched white light on three separate days in a randomized order; and Study 2 of 14 participants (8 females) during circadian misalignment induced by a simulated night shift protocol. Participants were healthy, free of medical disorders, medications, and illicit drugs. Participants maintained a consistent 8 h per night sleep schedule for one week as an outpatient prior to the study verified by wrist actigraphy, sleep diaries, and call-ins to a time stamped recorder. Participants consumed an outpatient energy balance research diet for three days prior to the study. The inpatient protocol for both studies consisted of an initial sleep disorder screening night. For study 1, this was followed by three standard days with 16 h scheduled wakefulness and 8 h scheduled nighttime sleep. For Study 2, it was followed by 16 h scheduled wake and 8 h scheduled sleep at habitual bedtime followed by three night shifts with 8 h scheduled daytime sleep. Energy expenditure was measured using whole-room indirect calorimetry. Constant posture bedrest conditions were maintained to control for energy expenditure associated with activity and the baseline energy balance diet was continued with the same exact meals across days to control for thermic effects of food. No significant impact of light exposure was observed on metabolic outcomes in response to daytime light exposure. Inter-individual variability in energy expenditure was systematic and ranged from substantial to almost perfect consistency during both nighttime sleep and circadian misalignment. Findings show robust and stable trait-like individual differences in whole body 24 h, waking, and sleep energy expenditure, 24 h respiratory quotient—an index of a fat and carbohydrate oxidation—during repeated assessments under entrained conditions, and also in 24 h and sleep energy expenditure during repeated days of circadian misalignment.

Circadian clocks synchronize the daily functions of organisms with environmental cues like light-dark cycles and feeding rhythms. The master clock in the suprachiasmatic nucleus in the hypothalamus of the brain and the many clocks in the periphery are organized in a hierarchical manner; the master clock synchronizes the peripheral clocks, and the peripheral clocks provide feedback to the master clock in return. Not surprisingly, it has been shown that circadian rhythms and metabolism are closely linked. Metabolic disorders like obesity have a large cost to the individual and society and they are marked by adipose tissue and mitochondrial dysfunction. Mitochondria are central to energy metabolism and have key functions in processes like ATP production, oxidative phosphorylation, reactive oxygen species production and Ca²⁺ homeostasis. Mitochondria also play an important role in adipose tissue homeostasis and remodeling. Despite the extensive research investigating the link between circadian clock and metabolism, the circadian regulation of adipose tissue and mitochondria has mostly been unexplored until recently, and the emerging data in this topic are the focus of this review.

Shift work is a risk factor for chronic diseases such as Type 2 diabetes. Food choice may play a role, however simply eating at night when the body is primed for sleep may have implications for health. This study examined the impact of consuming a big versus small snack at night on glucose metabolism. N = 31 healthy subjects (21–35 y; 18 F) participated in a simulated nightshift laboratory study that included one baseline night of sleep (22:00 h-07:00 h) and one night awake with allocation to either a big snack (2100 kJ) or small snack (840 kJ) group. The snack was consumed between 00:00–00:30 h and consisted of low fat milk, a sandwich, chips and fruit (big snack) or half sandwich and fruit (small snack). Subjects ate an identical mixed meal breakfast (2100 kJ) at 08:30 h after one full night of sleep and a simulated nightshift. Interstitial glucose was measured continuously during the entire study using Medtronic Continual Glucose Monitors. Only subjects with identical breakfast consumption and complete datasets were analysed (N = 20). Glucose data were averaged into 5-minute bins and area under the curve (AUC) was calculated for 90 min post-breakfast. Pre-breakfast, glucose levels were not significantly different between Day1 and Day2, nor were they different between snack groups (p > 0.05). A snack group by day interaction effect was found (F_1,16 = 5.36, p = 0.034) and post-hocs revealed that in the big snack group, AUC response to breakfast was significantly higher following nightshift (Day2) compared to Day1 (p = 0.001). This translated to a 20.8% (SEM 5.6) increase. AUC was not significantly different between days in the small snack group. Consuming a big snack at 00:00 h impaired the glucose response to breakfast at 08:30 h, compared to a smaller snack. Further research in this area will inform dietary advice for shift workers, which could include recommendations on how much to eat as well as content.

Objective

Melatonin, a neurohormone secreted by the pineal gland, controls circadian rhythmicity, modulates sleep and plays a role in glucose metabolism. Low secretion of nocturnal urinary 6-sulfatoxymelatonin (aMT6S) was associated with incident diabetes. Sleep disturbances have also been shown to be risk factors for diabetes. In this study, we explored the relationship between nocturnal urinary aMT6s and markers of glucose metabolism in prediabetes patients, considering sleep related factors.

Methods

Sixty two non-shift working patients with prediabetes [hemoglobin A1c (HbA1c) 5.7–6.49%] who were not on beta-blockers participated. Sleep duration and efficiency was recorded using 7-day actigraphy. Obstructive sleep apnea was evaluated using an overnight in-home monitoring device. Nocturnal urinary aMT6s/creatinine ratio was measured from an overnight urine sample. Oral glucose tolerance test (OGTT, 75-grams glucose) was performed, with measurements of insulin and glucose levels.

Results

Mean (SD) age was 55.3 (8.2) years and mean HbA1c level was 6.01 (0.2)%. Mean (SD) sleep duration 6.0 (0.9) h, sleep efficiency was 83.4 (6.6)% and a median (interquartile rage) apnea hypopnea index was 10.3 (3.6, 16.4). Median nocturnal urinary aMT6s was 17.4 (9.4, 28.2) ng/mg creatinine. Higher nocturnal urinary aMT6s significantly correlated with lower fasting insulin (p = 0.004), lower insulin response to OGTT (p = 0.027), and lower fasting and whole body insulin resistance as indicated by lower HOMA-IR and higher Matsuda insulin sensitivity index (p = 0.006 and p = 0.011, respectively), but it was not correlated with fasting glucose, glucose response to OGTT, or HbA1c. Sleep duration inversely correlated with HbA1c but no other correlations were found between other sleep variables and markers of glucose metabolism or nocturnal urinary aMT6s. After adjusting for body mass index, higher nocturnal urinary aMT6s significantly correlated with lower HOMA-IR (p = 0.025) and fasting insulin levels (p = 0.014).

Conclusion

Nocturnal urinary aMT6s inversely correlated with fasting insulin resistance and insulin levels in patients with prediabetes. These results support the role of melatonin in glucose metabolism.

Emotional processing is particularly sensitive to sleep deprivation, but research on the topic has been limited and prior studies have generally evaluated only a circumscribed subset of emotion categories. Here, we evaluated the effects of one night of sleep deprivation and a night of subsequent recovery sleep on the ability to identify the six most widely agreed upon basic emotion categories (happiness, surprise, fear, sadness, disgust, anger). Healthy adults (29 males; 25 females) classified a series of 120 standard facial expressions that were computer morphed with their most highly confusable expression counterparts to create continua of expressions that differed in discriminability between emotion categories (e.g., combining 70% happiness+30% surprise; 90% surprise+10% fear). Accuracy at identifying the dominant emotion for each morph was assessed after a normal night of sleep, again following a night of total sleep deprivation, and finally after a night of recovery sleep. Sleep deprivation was associated with significantly reduced accuracy for identifying the expressions of happiness and sadness in the morphed faces. Gender differences in accuracy were not observed and none of the other emotions showed significant changes as a function of sleep loss. Accuracy returned to baseline after recovery sleep. Findings suggest that sleep deprivation adversely affects the recognition of subtle facial cues of happiness and sadness, the two emotions that are most relevant to highly evolved prosocial interpersonal interactions involving affiliation and empathy, while the recognition of other more primitive survival-oriented emotional face cues may be relatively robust against sleep loss.

Previous studies have demonstrated that mean activity levels in the hippocampus oscillate on a circadian timescale, both at the single neuron and EEG level. This oscillation is also entrained by the availability of food, suggesting that the circadian modulation of hippocampal activity might comprise part of the recently discovered food-entrainable circadian oscillator (FEO). In order to determine whether the circadian oscillation in hippocampal activity is linked to activity in other brain regions, we recorded field-potential EEG from hippocampus and two cortical regions known to connect to hippocampus; the anterior cingulate cortex and the agranular insular cortex. These latter regions are involved in executive control (cingulate) and gustatory feedback (insula) and so are in a position where they could usefully contribute to, or benefit from, hippocampal memorial information in order to undertake task-related processing. We recorded EEG from these three regions for 20 m every hour for 58 consecutive hours in one continuous exposure to the recording environment. We found that there are regular and distinct increases in magnitude coherence between hippocampus and both cortical regions for EEG in both theta (6–12 Hz) and gamma (30–48 Hz) bands. These periods of increased coherence are spaced approximately one solar day apart, appear not to be specifically light-entrained, and are most apparent for gamma frequency activity. The gamma association between the two cortical regions shows the same temporal pattern of coherence peaks as the hippocampal-cortical coherences. We propose that these peaks in coherence represent the transient synchronization of temporally tagged memorial information between the hippocampus and other brain regions for which this information may be relevant. These findings suggest that the FEO involves coordinated activity across a number of brain regions and may underlie a mechanism via which an organism can store and recall salient gustatory events on a circadian timescale.

Self-imposed short sleep durations are increasingly commonplace in society, and have considerable health and performance implications for individuals. Reduced sleep duration over multiple nights has similar behavioural effects to those observed following acute total sleep deprivation, suggesting that lack of sleep affects brain function cumulatively. A link between habitual sleep patterns and functional connectivity has previously been observed, and the effect of sleep duration on the brain's intrinsic functional architecture may provide a link between sleep status and cognition. However, it is currently not known whether differences in habitual sleep patterns across individuals are related to changes in the brain's white matter, which underlies structural connectivity. In the present study we use diffusion–weighted imaging and a group comparison application of tract based spatial statistics (TBSS) to investigate changes to fractional anisotropy (FA) and mean diffusivity (MD) in relation to sleep duration and quality, hypothesising that white matter metrics would be positively associated with sleep duration and quality. Diffusion weighted imaging data was acquired from a final cohort of 33 (23–29 years, 10 female, mean 25.4 years) participants. Sleep patterns were assessed for a 14 day period using wrist actigraphs and sleep diaries, and subjective sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Median splits based on total sleep time and PSQI were used to create groups of shorter/longer and poorer/better sleepers, whose imaging data was compared using TBSS followed by post-hoc correlation analysis in regions identified as significantly different between the groups. There were significant positive correlations between sleep duration and FA in the left orbito-frontal region and the right superior corona radiata, and significant negative correlations between sleep duration and MD in right orbito-frontal white matter and the right inferior longitudinal fasciculus. Improved sleep quality was positively correlated with FA in left caudate nucleus, white matter tracts to the left orbito-frontal region, the left anterior cingulum bundle and the white matter tracts associated with the right operculum and insula, and negatively correlated with MD in left orbito-frontal white matter and the left anterior cingulum bundle. Our findings suggest that reduced cumulative total sleep time (cTST) and poorer subjective sleep quality are associated with subtle white matter micro-architectural changes. The regions we identified as being related to habitual sleep patterns were restricted to the frontal and temporal lobes, and the functions they support are consistent with those which have previously been demonstrated as being affected by short sleep durations (e.g., attention, cognitive control, memory). Examining how inter-individual differences in brain structure are related to habitual sleep patterns could help to she