Effects Of Circadian Misalignment Research Articles

Chronic circadian rhythm disorder induces heart failure with preserved ejection fraction-like phenotype through the Clock-sGC-cGMP-PKG1 signaling pathway

Emerging evidence has documented that circadian rhythm disorders could be related to cardiovascular diseases. However, there is limited knowledge on the direct adverse effects of circadian misalignment on the heart. This study aimed to investigate the effect of chronic circadian rhythm disorder on heart homeostasis in a mouse model of consistent jetlag. The jetlag model was induced in mice by a serial 8-h phase advance of the light cycle using a light-controlled isolation box every 4 days for up to 3 months. Herein, we demonstrated for the first time that chronic circadian rhythm disorder established in the mouse jetlag model could lead to HFpEF-like phenotype such as cardiac hypertrophy, cardiac fibrosis, and cardiac diastolic dysfunction, following the attenuation of the Clock-sGC-cGMP-PKG1 signaling. In addition, clock gene knock down in cardiomyocytes induced hypertrophy via decreased sGC-cGMP-PKG signaling pathway. Furthermore, treatment with an sGC-activator riociguat directly attenuated the adverse effects of jetlag model-induced cardiac hypertrophy, cardiac fibrosis, and cardiac diastolic dysfunction. Our data suggest that circadian rhythm disruption could induce HFpEF-like phenotype through downregulation of the clock-sGC-cGMP-PKG1 signaling pathway. sGC could be one of the molecular targets against circadian rhythm disorder-related heart disease.

Molecular-Level Dysregulation of Insulin Pathways and Inflammatory Processes in Peripheral Blood Mononuclear Cells by Circadian Misalignment.

Circadian misalignment due to night work has been associated with an elevated risk for chronic diseases. We investigated the effects of circadian misalignment using shotgun protein profiling of peripheral blood mononuclear cells taken from healthy humans during a constant routine protocol, which was conducted immediately after participants had been subjected to a 3-day simulated night shift schedule or a 3-day simulated day shift schedule. By comparing proteomic profiles between the simulated shift conditions, we identified proteins and pathways that are associated with the effects of circadian misalignment and observed that insulin regulation pathways and inflammation-related proteins displayed markedly different temporal patterns after simulated night shift. Further, by integrating the proteomic profiles with previously assessed metabolomic profiles in a network-based approach, we found key associations between circadian dysregulation of protein-level pathways and metabolites of interest in the context of chronic metabolic diseases. Endogenous circadian rhythms in circulating glucose and insulin differed between the simulated shift conditions. Overall, our results suggest that circadian misalignment is associated with a tug of war between central clock mechanisms controlling insulin secretion and peripheral clock mechanisms regulating insulin sensitivity, which may lead to adverse long-term outcomes such as diabetes and obesity. Our study provides a molecular-level mechanism linking circadian misalignment and adverse long-term health consequences of night work.

Pressure Building Against the Clock: The Impact of Circadian Misalignment on Blood Pressure.

Misalignment between the endogenous biological timing system and behavioral activities (i.e., sleep/wake, eating, activity) contributes to adverse cardiovascular health. In this review, we discuss the effects of recurring circadian misalignment on blood pressure regulation and the implications for hypertension development. Additionally, we highlight emerging therapeutic approaches designed to mitigate the negative cardiovascular consequences elicited by circadian disruption. Circadian misalignment elicited by work schedules that require individuals to be awake during the biological night (i.e., shift work) alters 24-h blood pressure rhythms. Mechanistically, circadian misalignment appears to alter blood pressure via changes in autonomic nervous system balance, variations to sodium retention, dysregulation of endothelial vasodilatory responsiveness, and activation of proinflammatory mechanisms. Recurring circadian misalignment produced by a mismatch in sleep timing on free days vs. work days (i.e., social jetlag) appears to have no direct effects on prevailing blood pressure levels in healthy adults; though, circadian disruptions resulting from social jetlag may increase the risk of hypertension through enhanced sympathetic activation and/or obesity. Furthermore, social jetlag assessment may be a useful metric in shift work populations where the magnitude of circadian misalignment may be greater than in the general population. Circadian misalignment promotes unfavorable changes to 24-h blood pressure rhythms, most notably in shift working populations. While light therapy, melatonin supplementation, and the timing of drug administration may improve cardiovascular outcomes, interventions designed to target the effects of circadian misalignment on blood pressure regulation are warranted.

Enhanced functional connectivity in the reward circuitry in healthy adults with weekend catch-up sleep.

We aimed to identify structural and functional changes in healthy adults with catch-up sleep (CUS), we applied seed-based functional connectivity (FC) analysis using resting-state functional magnetic resonance imaging (MRI). We hypothesized that deficits in reward processing could be a fundamental mechanism underlying the motivation of taking CUS. Then, 55 healthy adults voluntarily (34 with CUS and 21 without CUS) participated in this study. Voxel-based morphometry was performed to explore region of gray matter volume (GMV) difference between CUS and non-CUS groups. Between-group comparison of FC was then carried out using resting-state functional MRI analysis seeding at the region of volume difference. Moreover, the region of volume difference and the strength of FC were correlated with scores of questionnaires for reward-seeking behavior and clinical variables. CUS group had a higher reward-seeking tendency, and increased GMV in the bilateral nucleus accumbens and right superior frontal gyrus relative to non-CUS group. FC analysis seeding at the bilateral accumbens revealed increases of FC in the bilateral medial prefrontal cortex in CUS group compared to non-CUS group. The questionnaire scores reflecting the reward-seeking tendency were correlated with the FC strength between bilateral accumbens and medial prefrontal cortex. Our results indicate that CUS is associated with reward-seeking tendency and increased GMV and FC in regions responsible for reward network. Our findings suggest that enhanced reward network could be the crucial mechanism underlying taking CUS and might be implicated in the detrimental effects of circadian misalignment.

0215 Impact of sleep inertia on visual search performance during combined sleep restriction and circadian misalignment

Abstract Introduction Circadian phase and homeostatic sleep drive affect selective visual attention during sleep inertia (SI), a period of cognitive performance decrement upon awakening that dissipates with time. This study examined the combined effects of circadian misalignment and sleep restriction on visual search performance during SI. Methods Twenty adults (mean±standard deviation [SD] age 25.7±4.2 years; 12M, 8F) completed a 39-day protocol. Prior to a 4-day in-laboratory visit, participants maintained habitual 8h sleep schedules for 2 weeks at home. In-laboratory sleep opportunities (1 per day) were timed to induce varying levels of both circadian misalignment and sleep restriction: 8h on night 1, 3h on night 2, and 3h on mornings 3 and 4. After 3 days of recovery sleep at home (unscheduled), participants repeated the entire protocol. SI was assessed with the Serial Visual Search Task, a measure of selective visual attention, ~ 1, 16, and 31 min after electroencephalogram (EEG) verified awakening following each 3h sleep opportunity. The task required participants to determine whether a target was present or absent among nontarget distractors. Outcomes included median reaction times (RT) and number of missed targets. Sleep opportunities with ≥4.5 min of EEG-verified wakefulness in the 30 min prior to scheduled awakening were excluded from analysis. Data were analyzed with mixed-model ANOVA. Results Mean±SD average amount of wakefulness in the 30 min and 10 min prior to SI testing was 1.2±0.11 and 0.43±0.06 minutes, respectively. Following all sleep opportunities, median RT for overall correct responses and for correct response to target absent trials improved with time since awakening (all p<0.05). In contrast, median RT for correct responses to target present trials improved and number of missed targets worsened with time since awakening following the morning 3 sleep opportunity only (all p<0.05). Conclusion Reaction speed was impaired during SI regardless of circadian timing or level of homeostatic sleep drive, whereas missing targets appears to be dependent upon circadian phase and the level of homeostatic sleep debt. These findings have important implications for military and first responders. Support (If Any) Office of Naval Research MURI N00014-15-1-2809; NIH TR001082; Undergraduate Research Opportunities Grant, University of Colorado Boulder.

0001 Associations Between Circadian Factors and Travel Distance with Performance: A retrospective analysis of 2014-2018 National Basketball Association Data

Abstract Introduction Frequent travel across time zones and travelling long distances interferes with healthy sleep and disrupts the circadian system, often degrading athletic performance. National Basketball Association (NBA) players face a demanding travel schedule often requiring multiple games per week, with games spanning the continental United States. This investigation aimed to clarify the influence of circadian factors and travel distance on NBA performance using a dataset from the 2014-2018 seasons. Methods NBA (2014-2018) game data were acquired from an open-access source: (https://www.kaggle.com/ionaskel/nba-games-stats-from-2014-to-2018). Circadian variables of time zone change (TZ∆) and adjusted jet lag (AJL) were formulated, with quadratic versions utilized across analyses. TZ∆ captured circadian delay/advance based on travel for a game, with each TZ going eastward and westward reflected by -1 and +1, respectively. AJL advances TZ∆ by allowing acclimation to a novel TZ, with each day resulting in a 1-unit change towards circadian neutral. AJL is a season-long rolling summation, which was computed using two different travel approaches: Approach1 (AJL1) assumes travel the day before each game, whereas Approach2 (AJL2) was designed to prioritize being home. A standardized flight tracker determined travel distance for each game (GameDistance). Team ability differences, characterized as difference in season win percentages (SeasonWinPerDiff), served as an analytic covariate. Game point differential (PointDiff), defined as a team’s score minus their opponent’s score, and a team’s free throw percentage (FreeThrowPer) served as outcome variables. Linear mixed-effects modeling assessed univariate and multivariate associations, with games nested within both team and year. Results AJL2 (β = -0.63; p = .01) and GameDistance (β = -0.73; p<0.0001) significantly associated with PointDiff. TZ∆ (β = -0.002; p = .03), AJL1 (β = -0.002; p =.04) and GameDistance (β = -0.003; p = 0.007) significantly associated with FreeThrowPer. AJL2 and GameDistance maintained significant relationship with PointDiff in fully adjusted model that included AJL2, GameDistance, and SeasonWinPerDiff. Conclusion Results suggest that both circadian delay/advance and greater distance traveled for games negatively influence NBA performance, even when controlling for differences in team ability. Season travel and flight plans could be constructed to reduce the effects of circadian misalignment and travel distance. Support (If Any) None

Simultaneous Alteration of the Circadian Variation of Memory, Hippocampal Synaptic Plasticity, and Metabolism in a Triple Transgenic Mouse Model of Alzheimer's Disease.

Alzheimer’s disease (AD) is characterized by progressive memory deficits accompanied by synaptic and metabolic deficits, namely of mitochondrial function. AD patients also display a disrupted circadian pattern. Thus, we now compared memory performance, synaptic plasticity, and mitochondria function in 24-week-old non-transgenic (non-Tg) and triple transgenic male mice modeling AD (3xTg-AD) at Zeitgeber 04 (ZT-4, inactive phase) and ZT-16 (active phase). Using the Morris water maze test to minimize the influence of circadian-associated locomotor activity, we observed a circadian variation in hippocampus-dependent learning performance in non-Tg mice, which was impaired in 3xTg-AD mice. 3xTg-AD mice also displayed a lack of circadian variation of their performance in the reversal spatial learning task. Additionally, the amplitude of hippocampal long-term potentiation also exhibited a circadian profile in non-Tg mice, which was not observed in 3xTg-AD mice. Moreover, cerebral cortical synaptosomes of non-Tg mice also displayed a circadian variation of FCCP-stimulated oxygen consumption as well as in mitochondrial calcium retention that were blunted in 3xTg-AD mice. In sum, this multidimensional study shows that the ability to maintain a circadian oscillation in brain behavior, synaptic plasticity, and synaptic mitochondria function are simultaneously impaired in 3xTg-AD mice, highlighting the effects of circadian misalignment in AD.

Circadian Rhythms and Epilepsy: A Suitable Case for Absence Epilepsy.

Many physiological processes such as sleep, hormonal secretion, or thermoregulation, are expressed as daily rhythms orchestrated by the circadian timing system. A powerful internal clock mechanism ensures proper synchronization of vital functions within an organism on the one hand, and between the organism and the external environment on the other. Some of the pathological processes developing in the brain and body are subjected to circadian modulation as well. Epilepsy is one of the conditions which symptoms often worsen at a very specific time of a day. Variation in peak occurrence depends on the syndrome and localization of the epileptic focus. Moreover, the timing of some types of seizures is closely related to the sleep-wake cycle, one of the most prominent circadian rhythms. This review focuses on childhood absence epilepsy (CAE), a genetic generalized epilepsy syndrome, in which both, the circadian and sleep influences play a significant role in manifestation of symptoms. Human and animal studies report rhythmical occurrence of spike-wave discharges (SWDs), an EEG hallmark of CAE. The endogenous nature of the SWDs rhythm has been confirmed experimentally in a genetic animal model of the disease, rats of the WAG/Rij strain. Well-known detrimental effects of circadian misalignment were demonstrated to impact the severity of ongoing epileptic activity. SWDs are vigilance-dependent in both humans and animal models, occurring most frequently during passive behavioral states and light slow-wave sleep. The relationship with the sleep-wake cycle seems to be bidirectional, while sleep shapes the rhythm of seizures, epileptic phenotype changes sleep architecture. Circadian factors and the sleep-wake states dependency have a potential as add-ons in seizures' forecasting. Stability of the rhythm of recurrent seizures in individual patients has been already used as a variable which refines existing algorithms for seizures' prediction. On the other hand, apart from successful pharmacological approach, circadian hygiene including sufficient sleep and avoidance of internal desynchronization or sleep loss, may be beneficial for patients with epilepsy in everyday management of seizures.

Feeding Rhythms and the Circadian Regulation of Metabolism.

The molecular circadian clock regulates metabolic processes within the cell, and the alignment of these clocks between tissues is essential for the maintenance of metabolic homeostasis. The possibility of misalignment arises from the differential responsiveness of tissues to the environmental cues that synchronize the clock (zeitgebers). Although light is the dominant environmental cue for the master clock of the suprachiasmatic nucleus, many other tissues are sensitive to feeding and fasting. When rhythms of feeding behavior are altered, for example by shift work or the constant availability of highly palatable foods, strong feedback is sent to the peripheral molecular clocks. Varying degrees of phase shift can cause the systemic misalignment of metabolic processes. Moreover, when there is a misalignment between the endogenous rhythms in physiology and environmental inputs, such as feeding during the inactive phase, the body's ability to maintain homeostasis is impaired. The loss of phase coordination between the organism and environment, as well as internal misalignment between tissues, can produce cardiometabolic disease as a consequence. The aim of this review is to synthesize the work on the mechanisms and metabolic effects of circadian misalignment. The timing of food intake is highlighted as a powerful environmental cue with the potential to destroy or restore the synchrony of circadian rhythms in metabolism.

Circadian misalignment imposed by nocturnal feeding tends to increase fat deposition in pigs.

Misalignment of day/night and feeding rhythms has been shown to increase fat deposition and the risk for metabolic disorders in humans and rodents. In most studies, however, food intake and intake patterns are not controlled. We studied the effects of circadian misalignment on energy expenditure in pigs while controlling for food intake as well as intake patterns. Twelve groups of five male pigs were housed in respiration chambers and fed either during the day (10.00-18.00 hours; DF) or night (22.00-06.00 hours; NF), bihourly the same sequential meals, representing 15, 10, 25, 30 and 20 % of the daily allowance. Paired feeding was applied to ensure equal gross energy intake between treatments. Apparent total tract digestibility, energy balances and heat partitioning were measured and analysed using a mixed linear model. Apparent total tract energy and DM digestibility tended to be lower for NF-pigs than DF-pigs (P < 0·10). Heat production was 3 % lower for NF-pigs than DF-pigs (P < 0·026), increasing fat retention by 7 % in NF-pigs (P = 0·050). NF-pigs were less active than DF-pigs during the feeding period, but more active during the fasting period. RMR was greater for DF-pigs than NF-pigs during the fasting period. Methane production was 30 % greater in NF-pigs than DF-pigs (P < 0·001). In conclusion, circadian misalignment has little effect on nutrient digestion, but alters nutrient partitioning, ultimately increasing fat deposition. The causality of the association between circadian misalignment and methane production rates remains to be investigated.

Sex differences in the circadian misalignment effects on energy regulation

Shift work causes circadian misalignment and is a risk factor for obesity. While some characteristics of the human circadian system and energy metabolism differ between males and females, little is known about whether sex modulates circadian misalignment effects on energy homeostasis. Here we show-using a randomized cross-over design with two 8-d laboratory protocols in 14 young healthy adults (6 females)-that circadian misalignment has sex-specific influences on energy homeostasis independent of behavioral/environmental factors. First, circadian misalignment affected 24-h average levels of the satiety hormone leptin sex-dependently (P < 0.0001), with a ∼7% decrease in females (P < 0.05) and an ∼11% increase in males (P < 0.0001). Consistently, circadian misalignment also increased the hunger hormone ghrelin by ∼8% during wake periods in females (P < 0.05) without significant effect in males. Females reported reduced fullness, consistent with their appetite hormone changes. However, males reported a rise in cravings for energy-dense and savory foods not consistent with their homeostatic hormonal changes, suggesting involvement of hedonic appetite pathways in males. Moreover, there were significant sex-dependent effects of circadian misalignment on respiratory quotient (P < 0.01), with significantly reduced values (P < 0.01) in females when misaligned, and again no significant effects in males, without sex-dependent effects on energy expenditure. Changes in sleep, thermoregulation, behavioral activity, lipids, and catecholamine levels were also assessed. These findings demonstrate that sex modulates the effects of circadian misalignment on energy metabolism, indicating possible sex-specific mechanisms and countermeasures for obesity in male and female shift workers.

Night workers have lower levels of antioxidant defenses and higher levels of oxidative stress damage when compared to day workers

The effects of circadian misalignment and work shift on oxidative stress profile of shift workers have not been explored in the literature. The present study aimed to evaluate the role of shift work (day and night) and social jetlag - a measure of circadian misalignment - with oxidative stress markers. A cross-sectional study was performed with 79 men (21–65 years old, 27.56 ± 4.0 kg/m2) who worked the night shift (n = 37) or daytime (n = 42). The analyzed variables included anthropometric measures and determination of systemic levels of markers of oxidative damage and antioxidant defense. Social jetlag was calculated by the absolute difference between the mean sleep point on working and rest days. The night group presented higher systemic values of thiobarbituric acid reactive substances and hydrogen peroxide, and lower levels of nitrite, total antioxidant capacity, and catalase and superoxide dismutase activities in relation to the day group. However, social jetlag was not associated with oxidative stress-related biomarkers analyzed in the night group. These results suggest that the night worker has higher levels of oxidative stress damage and lower levels of antioxidant defenses, while social jetlag was not a possible responsible factor for this condition.

Effects of circadian misalignment on cognition in chronic shift workers

Shift work is associated with increased human operational errors, presumably due to the circadian timing system that inhibits optimal cognitive function during the night. Circadian misalignment, which is the misalignment between the circadian pacemaker and behavioral/environmental cycles, impairs cognitive performance in non-shift workers. However, it remains uncertain whether the adverse cognitive consequences of circadian misalignment are also observed in chronic shift workers. Thus, we investigated the effects of circadian misalignment on cognitive performance in chronic shift workers. Using a randomized, cross-over design that simulated day shift work (circadian alignment) and night shift work (circadian misalignment), we show that circadian misalignment increases cognitive vulnerability on sustained attention, information processing and visual-motor performance, particularly after more than 10 hours of scheduled wakefulness. Furthermore, their increased levels of subjective sleepiness and their decreased sleep efficiency were significantly associated with impaired sustained attention and visual-motor performance. Our data suggest that circadian misalignment dramatically deteriorates cognitive performance in chronic shift workers under circadian misalignment. This increased cognitive vulnerability may have important safety consequences, given the increasing number of nighttime jobs that crucially rely on the availability of cognitive resources.

Effects of circadian misalignment on sleep in mice

Circadian rhythms and sleep-wake history determine sleep duration and intensity, and influence subsequent waking. Previous studies have shown that T cycles - light-dark (LD) cycles differing from 24 h - lead to acute changes in the daily amount and distribution of waking and sleep. However, little is known about the long-term effects of T cycles. Here we performed continuous 10 day recording of electroencephalography (EEG), locomotor activity and core body temperature in C57BL/6 mice under a T20 cycle, to investigate spontaneous sleep and waking at baseline compared with when the circadian clock was misaligned and then re-aligned with respect to the external LD cycle. We found that the rhythmic distribution of sleep was abolished during misalignment, while the time course of EEG slow wave activity (1–4 Hz) was inverted compared to baseline. Although the typical light-dark distribution of NREM sleep was re-instated when animals were re-aligned, slow wave activity during NREM sleep showed an atypical increase in the dark phase, suggesting a long-term effect of T cycles on sleep intensity. Our data show that circadian misalignment results in previously uncharacterised long-term effects on sleep, which may have important consequences for behaviour.

Cardiac autonomic activity during simulated shift work.

Shift work leads to adverse health outcomes including increased risk of cardiovascular disease. Heart rate (HR) and heart rate variability (HRV) are measures of cardiac autonomic activity and markers of cardiovascular disease and mortality. To investigate the effects of shift work on cardiac autonomic activity, we assessed the influence of simulated night work on HR and HRV, and dissociated the direct effects of circadian misalignment from those of sleep displacement and altered physical activity patterns. A total of 29 subjects each participated in one of two in-laboratory, simulated shift work studies. In both studies, EKG was continuously monitored via Holter monitors to measure HR and the high frequency (HF) component of HRV (HF-HRV). We found endogenous circadian rhythmicity in HR and HF-HRV. Sleep and waking physical activity, both displaced during simulated night work, had more substantial, and opposite, effects on HR and HF-HRV. Our findings show systematic but complex, interacting effects of time of day, sleep/wake state, and physical activity on cardiac autonomic activity. These effects need to be taken into account when evaluating HR and HRV in shift work settings and when interpreting these measures of cardiac autonomic activity as markers of cardiovascular disease.

Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle

Circadian misalignment, such as in shift work, has been associated with obesity and type 2 diabetes. However, direct effects of circadian misalignment on skeletal muscle insulin sensitivity and the muscle molecular circadian clock have never been studied in humans. Here, we investigated insulin sensitivity and muscle metabolism in 14 healthy young lean men [age 22.4 ± 2.8 years; body mass index (BMI) 22.3 ± 2.1 kg/m2 (mean ± SD)] after a 3-d control protocol and a 3.5-d misalignment protocol induced by a 12-h rapid shift of the behavioral cycle. We show that short-term circadian misalignment results in a significant decrease in muscle insulin sensitivity due to a reduced skeletal muscle nonoxidative glucose disposal (rate of disappearance: 23.7 ± 2.4 vs. 18.4 ± 1.4 mg/kg per minute; control vs. misalignment; P = 0.024). Fasting glucose and free fatty acid levels as well as sleeping metabolic rate were higher during circadian misalignment. Molecular analysis of skeletal muscle biopsies revealed that the molecular circadian clock was not aligned to the inverted behavioral cycle, and transcriptome analysis revealed the human PPAR pathway as a key player in the disturbed energy metabolism upon circadian misalignment. Our findings may provide a mechanism underlying the increased risk of type 2 diabetes among shift workers.

0256 Circadian Rhythms, Impulsivity, and Adolescence: Effects Of Circadian Misalignment on the Neural Response During the Go/No-go Task In Human Adolescents

0256 Circadian Rhythms, Impulsivity, and Adolescence: Effects Of Circadian Misalignment on the Neural Response During the Go/No-go Task In Human Adolescents

The effect of chronotype (morningness/eveningness) on medical students' academic achievement in Sudan.

ObjectivesThere is increasing awareness about the effects of circadian misalignment on health and work. In the present study, we aimed to investigate the effects of chronotype on academic achievement among medical students.MethodsA cross-sectional comparative study was conducted among 140 medical students (64 who averaged an A grade and 76 who averaged a C grade) completing the clinical phase at the medical college of Omdurman University, Sudan. The participants were asked to sign a written informed consent and to keep a diary detailing their bedtime, wake-up time, sleep latency, and sleep duration during working days and weekends. Then, the participants were invited to respond to a questionnaire. The chronotype was calculated from the mid-sleep time during the weekend and sleep debt. Various sleep parameters were then compared between the two groups. A t-test and logistic regression analysis were used to test the statistical significance.ResultsThe medical students with average grades were more of the evening chronotype than the students with excellent grades (p < 0.05). Significant differences were found between the two groups regarding weekend bedtime, wake-up time, and sleep duration. In addition, significant differences were evident for weekday bedtime, sleep latency, and wake-up lag between weekdays and weekends. No differences were observed between the two groups during weekday wake-up time and sleep duration, chronotype between gender, and bedtime delay between weekdays and weekends (p > 0.05).ConclusionStudents whose average grade was a C were more likely to have a later bedtimes during weekdays and weekends, sleep more during weekends, and were more evening.

0208 CIRCADIAN MISALIGNMENT IMPACTS ON HUMAN COGNITIVE PERFORMANCE

Shift work increases the risk for disorders of sleep and human error. Overnight operations pose a challenge because our circadian biology promotes nocturnal sleep and daytime vigilance and performance, which may underlie cognitive vulnerability at night. Here we investigated if daily circadian misalignment, typical for night shift work, adversely impacts cognition across diverse cognitive domains. Thirteen healthy young individuals (27.8 ± 9.5 y; 7 men) underwent two 8-day protocols including either 4 days of circadian alignment (day shifts) or misalignment (night shifts; 12-h inverted behavioral/environmental cycles). Cognitive testing included tasks of sustained attention (Psychomotor Vigilance Task; PVT), cognitive throughput (Addition Task; ADD), information processing (Digit Symbol Substitution Task; DSST) visual-spatial performance (Unstable Tracking-Task; TKT) and declarative memory (Probed Recall Memory; PRM), all of which are sensitive to increased sleep pressure and circadian phase. Circadian misalignment over successive days increased cognitive vulnerability by ~10–20% on sustained attention, cognitive throughput, information processing and visual-motor performance, as compared circadian alignment. Attention, as indexed by PVT performance, was acutely impaired during the first 2 days of misalignment with subsequent improvement after 3 days (interaction of “circadian alignment/misalignment”, “day” and “time since awakening”, p=0.006). Conversely, learning, as indexed by changes in ADD, DSST and TKT performance, significantly improved across multiple days of circadian alignment, while no improvement occurred under misalignment (interaction of “circadian alignment/misalignment” and “day”, p<0.05). Lastly, we investigated if the effects of circadian misalignment on performance were also mediated by prior sleep-wake history. Accordingly, lower sleep efficiency in the sleep episode before cognitive testing significantly impaired performance (interaction of “sleep efficiency”, “circadian alignment/misalignment” and “night”; p<0.05). Our data indicate that daily circadian misalignment may explain cognitive vulnerabilities experienced by night workers, and provide a biological framework for the development of countermeasures against adverse cognitive effects in this vulnerable population. National Heart, Lung, and Blood Institute (NHLBI) Grant R01 HL094806, Clinical Translational Science Award UL1RR025758, and Brigham and Women’s Hospital from the National Center for Research Resources.

How jet lag impairs Major League Baseball performance

Laboratory studies have demonstrated that circadian clocks align physiology and behavior to 24-h environmental cycles. Examination of athletic performance has been used to discern the functions of these clocks in humans outside of controlled settings. Here, we examined the effects of jet lag, that is, travel that shifts the alignment of 24-h environmental cycles relative to the endogenous circadian clock, on specific performance metrics in Major League Baseball. Accounting for potential differences in home and away performance, travel direction, and team confounding variables, we observed that jet-lag effects were largely evident after eastward travel with very limited effects after westward travel, consistent with the >24-h period length of the human circadian clock. Surprisingly, we found that jet lag impaired major parameters of home-team offensive performance, for example, slugging percentage, but did not similarly affect away-team offensive performance. On the other hand, jet lag impacted both home and away defensive performance. Remarkably, the vast majority of these effects for both home and away teams could be explained by a single measure, home runs allowed. Rather than uniform effects, these results reveal surprisingly specific effects of circadian misalignment on athletic performance under natural conditions.