Heart rate variability rebound following exposure to persistent and repetitive sleep restriction.

While it is well established that slow-wave sleep electroencephalography (EEG) rebounds following sleep deprivation, very little research has investigated autonomic nervous system recovery. We examined heart rate variability (HRV) and cardiovagal baroreflex sensitivity (BRS) during four blocks of repetitive sleep restriction and sequential nights of recovery sleep. Twenty-one healthy participants completed the 22-day in-hospital protocol. Following three nights of 8-hr sleep, they were assigned to a repetitive sleep restriction condition. Participants had two additional 8-hr recovery sleep periods at the end of the protocol. Sleep EEG, HRV, and BRS were compared for the baseline, the four blocks of sleep restriction, and the second (R2) and third (R3) nocturnal recovery sleep periods following the last sleep restriction block. Within the first hour of each sleep period, vagal activation, as indexed by increase in high frequency (HF; HRV spectrum analysis), showed a rapid increase, reaching its 24-hr peak. HF was more pronounced (rebound) in R2 than during baseline (p < 0.001). The BRS increased within the first hour of sleep and was higher across all sleep restriction blocks and recovery nights (p = 0.039). Rebound rapid eye movement sleep was observed during both R2 and R3 (p = 0.004), whereas slow-wave sleep did not differ between baseline and recovery nights (p > 0.05). Our results indicate that the restoration of autonomic homeostasis requires a time course that includes at least three nights, following an exposure to multiple nights of sleep curtailed to about half the normal nightly amount.

Chronic exposure to insufficient sleep alters processes of pain habituation and sensitization.

Chronic pain conditions are highly comorbid with insufficient sleep. While the mechanistic relationships between the 2 are not understood, chronic insufficient sleep may be 1 pathway through which central pain-modulatory circuits deteriorate, thereby contributing to chronic pain vulnerability over time. To test this hypothesis, an in-laboratory model of 3 weeks of restricted sleep with limited recovery (5 nights of 4-hour sleep per night followed by 2 nights of 8-hour sleep per night) was compared with 3 weeks of 8-hour sleep per night (control protocol). Seventeen healthy adults participated, with 14 completing both 3-week protocols. Measures of spontaneous pain, heat-pain thresholds, cold-pain tolerance (measuring habituation to cold over several weeks), and temporal summation of pain (examining the slope of pain ratings during cold water immersion) were assessed at multiple points during each protocol. Compared with the control protocol, participants in the sleep-restriction protocol experienced mild increases in spontaneous pain (P < 0.05). Heat-pain thresholds decreased after the first week of sleep restriction (P < 0.05) but normalized with longer exposure to sleep restriction. By contrast, chronic exposure to restricted sleep was associated with decreased habituation to, and increased temporal summation in response to cold pain (both P < 0.05), although only in the past 2 weeks of the sleep-restriction protocol. These changes may reflect abnormalities in central pain-modulatory processes. Limited recovery sleep did not completely resolve these alterations in pain-modulatory processes, indicating that more extensive recovery sleep is required. Results suggest that exposure to chronic insufficient sleep may increase vulnerability to chronic pain by altering processes of pain habituation and sensitization.

Repeating patterns of sleep restriction and recovery: Do we get used to it?

Despite its prevalence in modern society, little is known about the long-term impact of restricting sleep during the week and 'catching up' on weekends. This common sleep pattern was experimentally modeled with three weeks of 5 nights of sleep restricted to 4h followed by two nights of 8-h recovery sleep. In an intra-individual design, 14 healthy adults completed both the sleep restriction and an 8-h control condition, and the subjective impact and the effects on physiological markers of stress (cortisol, the inflammatory marker IL-6, glucocorticoid receptor sensitivity) were assessed. Sleep restriction was not perceived to be subjectively stressful and some degree of resilience or resistance to the effects of sleep restriction was observed in subjective domains. In contrast, physiological stress response systems remain activated with repeated exposures to sleep restriction and limited recovery opportunity. Morning IL-6 expression in monocytes was significantly increased during week 2 and 3 of sleep restriction, and remained increased after recovery sleep in week 2 (p<0.05) and week 3 (p<0.09). Serum cortisol showed a significantly dysregulated 24h-rhythm during weeks 1, 2, and 3 of sleep restriction, with elevated morning cortisol, and decreased cortisol in the second half of the night. Glucocorticoid sensitivity of monocytes was increased, rather than decreased, during the sleep restriction and sleep recovery portion of each week. These results suggest a disrupted interplay between the hypothalamic-pituitary-adrenal and inflammatory systems in the context of repeated exposure to sleep restriction and recovery. The observed dissociation between subjective and physiological responses may help explain why many individuals continue with the behavior pattern of restricting and recovering sleep over long time periods, despite a cumulative deleterious physiological effect.

Sleep deprivation and stressors: evidence for elevated negative affect in response to mild stressors when sleep deprived.

Stress often co-occurs with inadequate sleep duration, and both are believed to impact mood and emotion. It is not yet known whether inadequate sleep simply increases the intensity of subsequent stress responses or interacts with stressors in more complicated ways. To address this issue, we investigated the effects of one night of total sleep deprivation on subjective stress and mood in response to low-stress and high-stress cognitive testing conditions in healthy adult volunteers in two separate experiments (total N = 53). Sleep was manipulated in a controlled, laboratory setting and stressor intensity was manipulated by changing difficulty of cognitive tasks, time pressure, and feedback about performance. Sleep-deprived participants reported greater subjective stress, anxiety, and anger than rested controls following exposure to the low-stressor condition, but not in response to the high-stressor condition, which elevated negative mood and stress about equally for both sleep conditions. These results suggest that sleep deprivation lowers the psychological threshold for the perception of stress from cognitive demands but does not selectively increase the magnitude of negative affect in response to high-stress performance demands.

Sleep loss and inflammation.

Controlled, experimental studies on the effects of acute sleep loss in humans have shown that mediators of inflammation are altered by sleep loss. Elevations in these mediators have been found to occur in healthy, rigorously screened individuals undergoing experimental vigils of more than 24h, and have also been seen in response to various durations of sleep restricted to between 25 and 50% of a normal 8h sleep amount. While these altered profiles represent small changes, such sub-clinical shifts in basal inflammatory cytokines are known to be associated with the future development of metabolic syndrome disease in healthy, asymptomatic individuals. Although the mechanism of this altered inflammatory status in humans undergoing experimental sleep loss is unknown, it is likely that autonomic activation and metabolic changes play key roles.

Effects of sleep restriction on adiponectin levels in healthy men and women.

OBJECTIVE: Population studies have consistently found that shorter sleep durations are associated with obesity and cardiovascular disease, particularly among women. Adiponectin is an adipocyte-derived, anti-inflammatory hormone that is related to cardiovascular disease risk. We hypothesized that sleep restriction would reduce adiponectin levels in healthy young adults. METHODS: 74 healthy adults (57% men, 63% African American, mean age 29.9years) completed 2 nights of baseline sleep at 10h time in bed (TIB) per night followed by 5 nights of sleep restricted to 4h TIB per night. An additional 8 participants were randomized to a control group that received 10h TIB per night throughout the study. Plasma adiponectin levels were measured following the second night of baseline sleep and the fifth night of sleep restriction or control sleep. RESULTS: Sleep restriction resulted in a decrease in plasma adiponectin levels among Caucasian women (Z=-2.19, p=0.028), but an increase among African American women (Z=-2.73, p=0.006). No significant effects of sleep restriction on adiponectin levels were found among men. A 2×2 between-group analysis of covariance on adiponectin change scores controlling for BMI confirmed significant interactions between sleep restriction and race/ethnicity [F(1,66)=13.73, p<0.001], as well as among sleep restriction, race/ethnicity and sex [F(1,66)=4.27, p=0.043)]. CONCLUSIONS: Inflammatory responses to sleep loss appear to be moderated by sex and race/ethnicity; observed decreases in adiponectin following sleep restriction may be one avenue by which reduced sleep duration promotes cardiovascular risk in Caucasian women.

Sleep restriction is associated with increased morning plasma leptin concentrations, especially in women.

STUDY OBJECTIVES: We evaluated the effects of sleep restriction on leptin levels in a large, diverse sample of healthy participants, while allowing free access to food. METHODS: Prospective experimental design. After 2 nights of baseline sleep, 136 participants (49% women, 56% African Americans) received 5 consecutive nights of 4 hours time in bed (TIB). Additionally, one subset of participants received 2 additional nights of either further sleep restriction (n = 27) or increased sleep opportunity (n = 37). Control participants (n = 9) received 10 hr TIB on all study nights. Plasma leptin was measured between 10:30 a.m. and 12:00 noon following baseline sleep, after the initial sleep-restriction period, and after 2 nights of further sleep restriction or recovery sleep. RESULTS: Leptin levels increased significantly among sleep-restricted participants after 5 nights of 4 hr TIB (Z = -8.43, p < .001). Increases were significantly greater among women compared to men (Z = -4.77, p < .001) and among participants with higher body mass index (BMI) compared to those with lower (Z = -2.09, p = .036), though participants in all categories (sex, race/ethnicity, BMI, and age) demonstrated significant increases. There was also a significant effect of allowed TIB on leptin levels following the 2 additional nights of sleep restriction (p < .001). Participants in the control condition showed no significant changes in leptin levels. CONCLUSIONS: These findings suggest that sleep restriction with ad libitum access to food significantly increases morning plasma leptin levels, particularly among women.

Increased amygdala fMRI activation after secretin administration.

It has recently been reported that secretin activates gene expression in the central nucleus of the amygdala in rats. To examine the neurophysiological effects of secretin on amygdalar activation in humans, the authors measured Blood Oxygen Level Dependent functional magnetic resonance imaging signal change during facial affect processing in a placebo-controlled double-blind study. The authors studied 12 healthy male subjects who were presented with three stimulus conditions: viewing happy, fearful, and neutral faces, before and after infusion with either secretin or placebo. To test whether treatment was associated with distinct patterns of activation, the two conditions (Pre and Post) were subjected to a subtraction analyses in SPM99 and hypotheses regarding the activation of the left and right amygdala were tested using a region-of-interest approach. Subtraction of treatment minus baseline activation during the fear condition yielded significant (p=.001) activation in the right amygdala and a nonsignificant increase in activation in the left amygdala. No significant differences were seen between the treatment conditions for the amygdala when viewing happy or neutral faces. These preliminary findings indicate that secretin may alter responsivity to affective stimuli. The presence of increased activation of the amygdala during the viewing of fearful faces is consistent with findings from animal studies and suggests a mechanism by which secretin may modulate social behavior.

Differences in regional blood volume during a 28-day period of abstinence in chronic cannabis smokers.

Cerebral blood volume (CBV) studies have provided important insight into the effects of illicit substances such as cannabis. The present study examined changes in regional blood volume in the frontal and temporal lobe, and the cerebellum during 28 days of supervised abstinence from cannabis. Dynamic susceptibility contrast MRI (DSCMRI) data were collected on 15 current, long-term cannabis users between 6 and 36 h after the subjects' last reported cannabis use (Day 0), and again after 7 and 28 days of abstinence. Resting state CBV images were also acquired on 17 healthy comparison subjects. The present findings demonstrate that at Day 7, cannabis users continued to display increased blood volumes in the right frontal region, the left and right temporal regions, and the cerebellum. However, after 28 days of abstinence, only the left temporal area and cerebellum showed significantly increased CBV values in cannabis users. These findings suggest that while CBV levels begin to normalize with continued abstinence from cannabis, specifically in frontal areas, other temporal and cerebellar brain regions show slower CBV decreases.

Altered regional blood volume in chronic cannabis smokers.

The quantitative measurement of cerebral perfusion is crucial for the study of both normal and impaired human brain function. Although cannabis is the most commonly abused illicit substance in the United States, its effects on cerebral blood volume (CBV) have not been fully examined. The objective of the present study was to examine differences in relative regional blood volume in focal regions of interest--including the frontal lobe, the temporal lobe, and the cerebellum--during a period of supervised abstinence from cannabis. Dynamic susceptibility contrast MRI data were collected on 12 current, long-term daily cannabis users between 6 and 36 hr after the subjects' last reported cannabis use. Resting-state CBV images were also acquired in 17 healthy comparison subjects. Data were acquired in the axial plane with a 1.5-Tesla GE Signa scanner following a bolus of gadolinium contrast agent. Cannabis users demonstrated significantly increased blood volumes in the right frontal area (p < .05), in the left temporal area (p < .005), and in the cerebellum (p < .005) relative to comparison subjects. Among the cannabis users, there were no significant correlations between regional blood volumes and either total lifetime episodes of smoking or urinary tetrahydrocannabinol concentrations. These findings have important implications for understanding the effects of chronic heavy cannabis use on brain function. It would be of interest to extend the investigation beyond 6-36 hr of abstinence from cannabis to determine whether increased CBV values persist for several weeks or eventually normalize.

Lack of hippocampal volume change in long-term heavy cannabis users.

The effects of cannabis smoking on the morphology of the hippocampus are still unclear, especially because previous human studies have examined primarily younger, shorter-term users. We used magnetic resonance imaging to investigate these effects in a group of 22 older, long-term cannabis users (reporting a mean [SD] of 20,100 [13,900] lifetime episodes of smoking) and 26 comparison subjects with no history of cannabis abuse or dependence. When compared to control subjects, smokers displayed no significant adjusted differences in volumes of gray matter, white matter, cerebrospinal fluid, or left and right hippocampus. Moreover, hippocampal volume in cannabis users was not associated with age of onset of use not total lifetime episodes of use. These findings are consistent with recent literature suggesting that cannabis use is not associated with structural changes within the brain as a whole or the hippocampus in particular.