Letter to the Editor: Prefrontal cortex hypoactivation in response to sleep-related pictures in shift workers.

Shift work can lead to mental health issues such as sleep disturbances and cognitive impairment. Neural activation in response to external sleep-related stimuli may vary according to shift work patterns. In this study, we investigated the differences in brain activity in response to sleep-related stimuli between shift-worker (SW) nurses and healthy controls (HCs), and we also assessed the relationships between sleep-related problems and brain activity. The hypothesis was that shift workers would exhibit altered activation in the prefrontal cortex (PFC) when processing sleep-related stimuli, reflecting attentional biases associated with sleep disturbances.Participants completed a cognitive task during functional magnetic resonance imaging that involved viewing sleep-related and neutral pictures. Subjective sleep was assessed using self-reported questionnaires and a 1-week sleep diary. Objective sleep parameters, along with the 24-h rest-activity rhythm, were evaluated via actigraphy conducted over 1 week. We analyzed group differences in the neural processing of sleep-related stimuli and conducted correlation analyses to explore the associations between brain activity and sleep parameters.This study included 44 SWs and 37 HCs. Compared to HCs, SWs demonstrated significantly lower activity in the dorsomedial prefrontal cortex (DMPFC) and lateral prefrontal cortex (LPFC) in response to sleep-related pictures than neutral pictures. DMPFC activity was significantly negatively correlated with subjective sleep problems (e.g., self-reported insomnia and fatigue), whereas LPFC activity was strongly correlated with actigraphy-measured 24-h rest-activity rhythm parameters (e.g., a robust 24-h rhythm).The decreased activation of the prefrontal cortex in response to sleep-related stimuli in SWs may reflect diminished attentional control over sleep and increased rumination on intrusive sleep-related thoughts. These findings enhance our understanding of the neurobiological mechanisms underlying sleep-related issues in SWs and may inform interventions to mitigate mental health problems in this population.

The mechanisms that contribute to emotion dysregulation in anxiety disorders are not well understood. Two common disorders, generalized anxiety disorder (GAD) and panic disorder (PD), were examined to test the hypothesis that both disorders are characterized by hypo-activation in prefrontal cortex (PFC) during emotion regulation. A competing hypothesis that GAD in particular is characterized by PFC hyper-activation during emotion regulation (reflecting overactive top-down control) was also evaluated. Method Twenty-two medication-free healthy control (HC), 23 GAD, and 18 PD participants underwent functional magnetic resonance imaging (fMRI) during a task that required them to reappraise (i.e. reduce) or maintain emotional responses to negative images. GAD participants reported the least reappraisal use in daily life, and reappraisal use was inversely associated with anxiety severity and functional impairment in these participants. During fMRI, HCs demonstrated greater activation during both reappraisal and maintenance than either GAD or PD participants (who did not differ) in brain areas important for emotion regulation (e.g. dorsolateral and dorsomedial PFC). Furthermore, across all anxious participants, activation during reappraisal in dorsolateral and dorsomedial PFC was inversely associated with anxiety severity and functional impairment. Emotion dysregulation in GAD and PD may be the consequence of PFC hypo-activation during emotion regulation, consistent with insufficient top-down control. The relationship between PFC hypo-activation and functional impairment suggests that the failure to engage PFC during emotion regulation may be part of the critical transition from dispositionally high anxiety to an anxiety disorder.

BackgroundGeneralized anxiety disorder (GAD) is closely associated with emotional dysregulation. Patients with GAD tend to overreact to emotional stimuli and are impaired in emotional regulation. Using emotional regulation task, studies have found hypo-activation in prefrontal cortex (PFC) of GAD patients and concluded with inadequate top-down control. However, results remain inconsistent concerning PFC and limbic area’s reactivity to emotional stimuli. What’s more, only a few studies aim to identify how limbic area interacts with PFC in GAD patients. The current study aims to identify the difference in PFC-limbic circuitry response to emotional stimuli between GAD patients and healthy controls (HCs) from the perspective of brain network. Through brain network analysis, it revealed the connectivity between limbic area and PFC, and moreover, the orientation of connectivity, all of which gave a better test of inadequate top-down control hypothesis.MethodsDuring fMRI scanning, participants were required to complete an emotional face identification task (fearful, neutral, happy facial expression). 30 participants (16 GAD patients, 14 HCs) were included in the formal analysis. A Bayesian-network based method was used to identify the brain network consisting of several pre-hypothesized regions of interest (ROIs) under each condition (negative, positive, neutral). In total, six graphs were obtained. Each of them represented the brain network that was common to the group under corresponding condition.ResultsResults revealed that GAD patients showed more bottom-up connection but less top-down connection regardless of condition, relative to HCs. Also, the insula was more connected but the amygdala was less connected regardless of condition, relative to HCs. the results also revealed a very different brain network response between GAD patients and HCs even under neutral condition.ConclusionsMore bottom-up connection but less top-down connection may indicate that GAD patients are insufficient in top-down control, in keeping with inadequate top-down control hypothesis. The more connected insula may indicate GAD patients’ abnormality in interoception processing. Relative to HCs, distinct brain network response pattern in GAD patients under neutral condition suggests GAD patients’ abnormality in distinguishing safety from threat and intolerance of uncertainty.

Both social behavior and stress responses rely on the activity of the prefrontal cortex (PFC) and basolateral nucleus of the amygdala (BLA) and on cholinergic transmission. We previously showed in adult C57BL/6J (B6) mice that social interaction has a buffering effect on stress-related prefrontal activity, depending on the β2-/- cholinergic nicotinic receptors (nAChRs, β2-/- mice). The latency for this buffer to emerge being short, we question here whether the associated brain plasticity, as reflected by regional c-fos protein quantification and PFC-BLA functional connectivity, is modulated by time. Overall, we show that time normalized the stress-induced PFC hyperactivation in B6 mice and PFC hypo-activation in β2-/- mice, with no effect on BLA. It also triggered a multitude of functional links between PFC subareas, and between PFC and BLA in B6 mice but not β2-/- mice, showing a central role of nAChRs in this plasticity. Coupled with social interaction and time, stress led to novel and drastic diminution of functional connectivity within the PFC in both genotypes. Thus, time, emotional state, and social behavior induced dissociated effects on PFC and BLA activity and important cortico-cortical reorganizations. Both activity and plasticity were under the control of the β2-nAChRs.

Major depressive disorder (MDD) is a widespread psychiatric condition, recognized as the third leading cause of global disease burden in 2008. In the context of MDD, alterations in synaptic transmission within the prefrontal cortex (PFC) are associated with PFC hypoactivation, a key factor in cognitive function and mood regulation. Given the high energy demands of the central nervous system, these synaptic changes suggest a metabolic imbalance within the PFC of MDD patients. However, the cellular mechanisms underlying this metabolic dysregulation remain not fully elucidated. This study employs single-nucleus RNA sequencing (snRNA-seq) data to predict metabolic alterations in the dorsolateral PFC (DLPFC) of MDD patients. Our analysis revealed cell type-specific metabolic patterns, notably the disruption of oxidative phosphorylation and carbohydrate metabolism in the DLPFC of MDD patients. Gene set enrichment analysis based on human phenotype ontology predicted alterations in serum lactate levels in MDD patients, corroborated by the observed decrease in lactate levels in MDD patients compared to 47 age-matched healthy controls (HCs). This transcriptional analysis offers novel insights into the metabolic disturbances associated with MDD and the energy dynamics underlying DLPFC hypoactivation. These findings are instrumental for comprehending the pathophysiology of MDD and may guide the development of innovative therapeutic strategies.

The effect of transcranial direct current stimulation (tDCS) on food craving, reward and appetite in a healthy population

BackgroundAlthough numerous studies have investigated the neurobiology and neuroendocrinology of posttraumatic stress disorder (PTSD) after single finished trauma, studies on PTSD under ongoing threat are scarce and it is still unclear whether these individuals present similar abnormalities.ObjectiveThe purpose of this review is to present the neurobiological and neuroendocrine findings on PTSD under ongoing threat. Ongoing threat considerably affects PTSD severity and treatment response and thus disentangling its neurobiological and neuroendocrine differences from PTSD after finished trauma could provide useful information for treatment.MethodEighteen studies that examined brain functioning and cortisol levels in relation to PTSD in individuals exposed to intimate partner violence, police officers, and fire fighters were included.ResultsHippocampal volume was decreased in PTSD under ongoing threat, although not consistently associated with symptom severity. The neuroimaging studies revealed that PTSD under ongoing threat was not characterized by reduced volume of amygdala or parahippocampal gyrus. The neurocircuitry model of PTSD after finished trauma with hyperactivation of amygdala and hypoactivation of prefrontal cortex and hippocampus was also confirmed in PTSD under ongoing threat. The neuroendocrine findings were inconsistent, revealing increased, decreased, or no association between cortisol levels and PTSD under ongoing threat.ConclusionsAlthough PTSD under ongoing threat is characterized by abnormal neurocircuitry patterns similar to those previously found in PTSD after finished trauma, this is less so for other neurobiological and in particular neuroendocrine findings. Direct comparisons between samples with ongoing versus finished trauma are needed in future research to draw more solid conclusions before administering cortisol to patients with PTSD under ongoing threat who may already exhibit increased endogenous cortisol levels.Highlights of the articleWe reviewed the neurobiological and neuroendocrine findings in PTSD under ongoing threat.PTSD under ongoing threat demonstrated similar brain abnormalities as PTSD after finished trauma.Several studies found increased cortisol levels in PTSD under ongoing threat.Hydrocortisone administration might not be beneficial for individuals with PTSD under ongoing threat with elevated endogenous cortisol levels.Direct comparisons between ongoing versus finished trauma are needed to provide robust conclusions and clinical recommendations.

Introduction Shift work is known to have a negative impact on a wide range of health problems such as sleep disturbance, cognitive impairment, and emotional disorders (e.g., anxiety and depression). It is important to understand underlying mechanisms for negative impact of shift work on health problems. This study aimed to investigate psychological and neural mechanisms associated with shift work. Methods Thirty six shift workers (28 females, age = 29.9 ± 7.4) and 35 non-shift workers (20 females, age = 30.5 ± 5.5) participated in this study. They were performing the word Stroop task during fMRI scanning. This task included sleep-related words and negative words to investigate neural substrates associated with sleep-related information and emotional information processing. Neutral words were included as control stimuli. The participants also completed questionnaires assessing sleep-related problems such as Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale, and emotion-related problems such as Beck Depression Inventory and Beck Anxiety Inventory. Two-sample t-tests were conducted to find group differences in self-report measures and neural response to sleep-related words and negative words compared to neutral words. Results Relative to non-shift workers, shift workers showed greater sleep disturbance (i.e., higher PSQI), but they did not show any evidence of emotion-related problems. Shift workers also demonstrated greater neural response to negative words (vs. neutral words) in several prefrontal regions (e.g., dorsal anterior cingulate cortex and dorsolateral prefrontal cortex), anterior insula and caudate compared to non-shift workers. However, shift workers did not show significantly different neural response to sleep-related words (vs. neutral words) compared to non-shift workers. Conclusion The result from this study provides supporting evidence that shift work is associated with subjective sleep disturbance. Shift workers’ heightened neural response to negative information may reflect their increased sensitivity to negative information, that may contribute to sleep disturbance. Support Brain Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (Study No.: 2016M3C7A1904338 and NRF-2018R1D1A1B07049704).

Millions of people worldwide work during the night, resulting in disturbed circadian rhythms and sleep loss. This may cause deficits in cognitive functions, impaired alertness and increased risk of errors and accidents. Disturbed circadian rhythmicity resulting from night shift work could impair brain function and cognition through disrupted synthesis of proteins involved in synaptic plasticity and neuronal function. Recently, the circadian transcription factor brain-and-muscle arnt-like protein 1 (BMAL1) has been identified as a promoter of mRNA translation initiation, the most highly regulated step in protein synthesis, through binding to the mRNA “cap”. In this study we investigated the effects of simulated shift work on protein synthesis markers. Male rats (n = 40) were exposed to forced activity, either in their rest phase (simulated night shift work) or in their active phase (simulated day shift work) for 3 days. Following the third work shift, experimental animals and time-matched undisturbed controls were euthanized (rest work at ZT12; active work at ZT0). Tissue lysates from two brain regions (prefrontal cortex, PFC and hippocampus) implicated in cognition and sleep loss, were analyzed with m7GTP (cap) pull-down to examine time-of-day variation and effects of simulated shift work on cap-bound protein translation. The results show time-of-day variation of protein synthesis markers in PFC, with increased protein synthesis at ZT12. In the hippocampus there was little difference between ZT0 and ZT12. Active phase work did not induce statistically significant changes in protein synthesis markers at ZT0 compared to time-matched undisturbed controls. Rest work, however, resulted in distinct brain-region specific changes of protein synthesis markers compared to time-matched controls at ZT12. While no changes were observed in the hippocampus, phosphorylation of cap-bound BMAL1 and its regulator S6 kinase beta-1 (S6K1) was significantly reduced in the PFC, together with significant reduction in the synaptic plasticity associated protein activity-regulatedcytoskeleton-associated protein (Arc). Our results indicate considerable time-of-day and brain-region specific variation in cap-dependent translation initiation. We concludethat simulated night shift work in rats disrupts the pathways regulating the circadian component of the translation of mRNA in the PFC, and that this may partly explain impaired waking function during night shift work.

BackgroundIntensive care unit (ICU) medical staffs undergoing sleep deprivation with perennial night shift work were usually at high risk of depression. However, shift work on depression-related resting-state functional magnetic resonance imaging was still not fully understood. The objective of this study was to explore the effects of sleep deprivation in ICU medical staffs after one night of shift work on brain functional connectivity density (FCD) and Hamilton Depression Rating Scale (HAMD) scores. Also, serum neurotransmitter concentrations of serotonin (5-HT) and norepinephrine (NE) were obtained simultaneously.MethodsA total of 21 ICU medical staffs without psychiatric history were recruited. All participants received HAMD score assessment and resting-state functional magnetic resonance imaging scans at two time points: one at rested wakefulness and the other after sleep deprivation (SD) accompanied with one night of shift work. Global FCD, local FCD, and long-range FCD (lrFCD) were used to evaluate spontaneous brain activity in the whole brain. In the meantime, peripheral blood samples were collected for measurement of serum 5-HT and NE levels. All these data were acquired between 7:00 and 8:00 am to limit the influence of biological rhythms. The correlations between the FCD values and HAMD scores and serum levels of neurotransmitters were analyzed concurrently.ResultsFunctional connectivity density mapping manifested that global FCD was decreased in the right medial frontal gyrus and the anterior cingulate gyrus, whereas lrFCD was decreased mainly in the right medial frontal gyrus. Most of these brain areas with FCD differences were components of the default mode network and overlapped with the medial prefrontal cortex. The lrFCD in the medial frontal gyrus showed a negative correlation with HAMD scores after SD. Compared with rested wakefulness, serum levels of 5-HT and NE decreased significantly, whereas HAMD scores were higher after SD within subjects.ConclusionsOur study suggested that sleep deprivation after night shift work can induce depressive tendency in ICU medical staffs, which might be related to alterative medial prefrontal cortex, raised HAMD scores, and varying monoamine neurotransmitters.

Received from the Anesthesia Service, VA Palo Alto Health Care System, Department of Anesthesia, Stanford University School of Medicine, Palo Alto, California; the Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut; and the Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia.HEALTHCARE delivery takes place 24 h a day, 7 days a week, and is colloquially termed a “24/7” operation. Anesthesia providers are required to deliver critical around-the-clock care to a variety of patients. This parallels the situation in many other domains that provide such services, e.g ., transportation, law enforcement, communications, fire fighting, technology, manufacturing, and the military. Even “convenience” industries (e.g ., gas stations and grocery stores) now provide uninterrupted access. These continuous operational demands present unique physiologic challenges to the humans who are called on to provide safe operations within these systems. Human physiologic design dictates circadian patterns of alertness and performance and includes a vital need for sleep. Human requirements for sleep and a stable circadian clock can be, and often are, in direct opposition to the societal demand for continuous operations.Recently, patient safety has taken center stage in health care. The Institute of Medicine's report “To Err Is Human: Building a Safer Health System,” revealed that medical errors contribute to many hospital deaths and serious adverse events. 1The response to this report was widespread and included the Quality Interagency Coordination Task Force's response to the President of the United States, “Doing What Counts for Patient Safety: Federal Actions to Reduce Medical Errors and Their Impact.”∥2This report listed more than 100 action items to be undertaken by federal agencies to improve quality and reduce medical errors. One action promised by the Agency for Healthcare Research and Quality was “the development and dissemination of evidence-based, best safety practices to provider organizations.” In addition to the multiple recommendations to improve patient safety, the report from the Agency for Healthcare Research and Quality included a review chapter on sleep, fatigue, #and medical errors. **There is evidence that the issue of fatigue in health care is coming to prominence on a national level. In April 2001, Public Citizen (a consumer and health advocacy group) and a consortium of interested parties petitioned the Occupational Safety and Health Administration to implement new regulations on resident work hours (table 1). The primary intent of the regulations is to provide more humane working conditions, which the petitioners declare will result in a better standard of care for all patients. Also, the Patient and Physician Safety and Protection Act of 2001, which would limit resident physician work hours, was introduced in Congress. Recently, the Accreditation Council on Graduate Medical Education, the accrediting organization for residency training programs in the United States, has approved common program requirements for resident duty and rest hours that will take effect in July 2003. ††The potential impact of sleep loss and fatigue, specifically among anesthesiologists, has received only sporadic attention. 3,4The cognitive demands of intraoperative patient care requires an iteration of data collection, evaluation of its relevance to patient status, development and implementation of plans to maintain the desired patient status, and monitoring the outcome of interventions. These complex tasks require sustained attention or “vigilance” and are particularly vulnerable to the effects of fatigue. 5–8The purpose of this article is to review the physiology of prolonged work cycles and fatigue, to relate this to the work milieu of the practice of anesthesiology, and suggest economically feasible recommendations to mitigate the effects of fatigue.Sleep loss and disruption of circadian rhythm that result from arduous work schedules can lead to reduced safety, performance, and health. While some of these outcomes are well documented, much remains to be learned about the short- and long-term effects of sleep and circadian disruption. The following nonmedical examples of the safety, performance, and health risks associated with around-the-clock operations illustrate the increasing human and economic costs related to ignoring the effects of these physiologic disruptions.There have been several high-profile accidents where fatigue was identified as either causal or contributory. For example, although alcohol is often cited as the central reason in the Exxon Valdez marine grounding, the National Transportation Safety Board investigation identified fatigue as one of the probable causes of the accident. 9Similarly, circadian factors were identified as contributing to the errors that resulted in the nuclear accidents at Three Mile Island and Chernobyl. 10,11Fatigue resulting from the work–rest patterns of managers was also acknowledged as an important component of the flawed decision-making that contributed to the space shuttle Challenger accident. 12Fatigue-related accidents have been identified in every mode of transportation and can be found in many around-the-clock operational settings. Clearly, there are a variety of adverse outcomes such as economic costs, disrupted service, injuries, and even fatalities that result from these accidents. For example, the Exxon Valdez grounding was associated with environmental cleanup operations and legal cases involving billions of dollars, and Space Shuttle operations were suspended for several years after the Challenger disaster.Fatigue-related safety risks affect us at both individual and societal levels. A recent poll by the National Sleep Foundation indicated that one of two drivers reported having driven while drowsy in the past year, ‡‡and one of five acknowledged having “nodded off” while driving. Fatigue contributes to 100,000 crashes annually that result in 76,000 injuries and 1,550 fatalities, according to estimates by the National Highway Traffic Safety Administration. 13Recently, an international group of scientists estimated that fatigue is causal in 15–20% of all transportation accidents, that official statistics underestimate the scope of the problem, and that fatigue exceeds the combined contribution of alcohol and drugs in transportation accidents. 14Fatigue caused by sleep loss and circadian disruption can degrade performance and reduce many aspects of human capability. 15Known performance effects include reduced attention–vigilance, impaired memory and decision-making, prolonged reaction time, and disrupted communications. 16–20These degraded performance outcomes create a situation where there is increased risk for the occurrence of errors, critical incidents, and accidents. 15Fatigue also creates increased performance variability, with cyclic reductions in alertness and performance. 21Fatigued workers have a tendency to slow down work processes to maintain accuracy, a classic effect known as the speed-accuracy trade-off. 22It takes only a moment of reduced performance during a critical task to have a negative outcome. Even if a lapse in performance occurs during a noncritical task, the system vulnerability shifts to a less safe state.Fatigue-related accidents are sometimes considered to be a result of falling asleep. Performance gaps can be the result of these “microsleeps,” which are brief, uncontrolled, and spontaneous episodes of physiologic sleep. 8There can be significant performance reductions that are sufficient to create safety risks prior to and immediately after the occurrence of a microsleep. 23,24Slowed cognitive throughput, reduced memory, slowed reaction time, lowered optimal responding, and attention lapses can create an increased opportunity for errors to occur. 25Consider the circumstance where an anesthesiologist's response to an alarm is slowed and an inappropriate decision guides an incorrect action. The practitioner may have been “awake,” but fatigue-related performance decrements could be contributory to the occurrence of any error, incident, or accident that resulted from the action.The decrement in psychomotor performance resulting from sleep deprivation have been correlated with those resulting from the impairments associated with ethanol ingestion. 26Performance on a hand–eye tracking task declined such that the impairment was equivalent to a blood alcohol level of 0.05% after 17 h of wakefulness. At 24 h of sustained wakefulness, the impairment in psychomotor function was equivalent to a blood alcohol concentration of 0.1%, at or above the legal limit for driving in most states. These data could be useful to help quantify fatigue-related effects with a drug that the public and policy makers better understand.Specific clinical skills of importance to the practice of anesthesiology deteriorate as a result of fatigue. On a simulated monitoring task where subjects were asked to monitor and record the time of significant deviation of clinical variables (e.g ., heart rate, blood pressure), Denisco et al . reported lower “vigilance scores” in the group that had been on call. 27The ability to interpret electrocardiographic changes and to do simple mathematical calculations is compromised among sleep-deprived house officers. 28The speed and quality of intubation was diminished among emergency department physicians working the night shift as compared with their performance while working during the day. 29,30Many of the fatigue-related decrements in performance identified in residents are potentially worse in older physicians. Aging is associated with a tendency toward early awakening, an exaggerated dip in arousal midafternoon, and a decreased tolerance of late-night and shift work. 31The unique demands of night call on older anesthesiologists are more onerous than those found in other specialties. 32Among recently retired anesthesiologists, night call was identified as the most stressful aspect of anesthetic practice and the most important reason for retirement. 33,34Beyond the safety risks and performance decrements associated with sleep loss and circadian disruption, there are a variety of personal health concerns. Several studies have shown that long-term exposure to shift work represents an independent risk factor for the development of both gastrointestinal and cardiovascular diseases. 35–39A recent study found that women working the night shift had a 60% greater risk for breast cancer compared with women who never worked the late shift. 40There is evidence that some adverse pregnancy outcomes are related to working conditions. 41A meta-analysis of 29 studies, including more than 160,000 women, evaluated the association of physically demanding work, prolonged standing, long work hours, and cumulative “fatigue score” with preterm delivery, pregnancy-induced hypertension, and small-for-gestational-age infants. There was a positive association between physically demanding work and preterm births, pregnancy-induced hypertension, and delivery of small-for-gestational-age infants. Shift work alone was found to increase the incidence of preterm births. 41There is evidence that sleep restriction alters physiologic function. Significant detrimental effects on immune function can be found after a few days of total sleep deprivation or after several days of partial sleep loss. 42,43Sleep restriction of 4 h per night for six nights is associated with harmful effects on carbohydrate metabolism and endocrine function. 44This degree of sleep restriction resulted in abnormal glucose tolerance, decreased thyrotropin concentrations, increased evening cortisol concentrations, and increased sympathetic nervous system activity (as measured by heart rate variability). Sleep deprivation and circadian disruption affect cerebral metabolic and cognitive function. In a study of changes in regional cerebral glucose utilization (i.e ., positron emission tomography) during 85 h of consecutive sleep loss, decreases in cerebral metabolic rate were observed primarily in the thalamus and prefrontal and posterior parietal cortices. Alertness and cognitive performance declined in association with these brain deactivations. 45A recent study of aircrew members suggests there may be a linkage between long-term exposure to time-zone changes (i.e ., circadian disruption), temporal lobe atrophy, and deficits in learning and memory. 46Investigations using functional magnetic resonance imaging technology contradict some of the aformentioned findings and reveal compensatory changes of increased activation in the prefrontal cortex and parietal lobes during verbal learning after sleep deprivation. 47–50Studies show altered mortality with sleep loss and circadian disruption. Circadian disruption in hamsters and Drosophila reduce life span from 11 to 15%. 51,52A prospective investigation of more than one million individuals conducted by the American Cancer Society found that men who reported “usual” daily sleep times of less than 4 h were 2.8 times more likely to have died within a 6-year follow-up as men who obtained 7.0–7.9 h of sleep. 53The risk for women was increased by 48%. Conversely, men and women who reported sleeping 10 h or more per day had about 1.8 times the mortality rate of those who reported 7.0–7.9 h of sleep.The two primary determinants that underlie fatigue and interact in a dynamic manner are sleep homeostasis and circadian rhythms. 54An individual's level of alertness (e.g ., on the job) or potential for sleep (e.g ., during a rest period) will be determined by a complex interaction of these factors. Performance and alertness decrements may occur when either of these elements is disrupted. 55Factors other than fatigue, such as workload, environment, stress, boredom, motivation, and professionalism, also influence the ability to perform. 4In addition, there are large interindividual differences on the effects of fatigue. 56Sleep serves a vital physiologic need. 57Like other basic physiologic requirements such as food and water, sleep plays a fundamental role in survival. Sleep homeostasis is the balance between sleep need and quality and quantity of sleep obtained by an individual. On average, the adult human requirement for sleep appears to be greater than 8 h (8 h:14 min) per 24-h period. 58,59The range of sleep need varies from 6 to 10 h, and this requirement is probably genetically determined and cannot be “trained” to a different sleep need. 60Estimates suggest that most American adults obtain about 1–1.5 h less sleep than needed. §§This lost sleep accumulates to produce a “sleep debt.”8,58For example, an individual who obtains 1.5 h less sleep per night over a 5-day work week will begin the weekend with 7.5 h of sleep debt. This deficit is roughly equivalent to the loss of a full night of sleep and requires about two nights of at least 8 h of sleep for recovery. 20Sleep debts are not repaid hour for hour, but instead through an increase in deep sleep or nonrapid eye movement stages 3 and 4. 20A variety of factors can affect sleep quantity and quality. Perhaps some of the most dramatic changes in sleep occur as a normal function of aging. Approaching age 50 and beyond, sleep becomes more disrupted with frequent awakenings. There are reduced amounts of deep sleep, and sleep becomes less consolidated. 61Nocturia in men and menopausal symptoms in women are likely to contribute to sleep disturbances in older individuals. There are also age-related increases in complaints of insomnia and depression that negatively impact sleep. Sleep need does not necessarily decrease with age, and increased daytime sleepiness can be the consequence of reduced sleep quantity and quality. There have been no formal studies assessing whether these changes in sleep quantity and quality affect the performance of older anesthesia providers.There are approximately 90 known sleep disorders that have been described and classified in a diagnostic nosology. 62The causes for these disorders range from physiologic to psychological to environmental. Some sleep disorders are relatively prevalent in the population and have well-documented negative effects on waking alertness and performance. 63–65Often, the affected individual is unaware of their disorder, and the bed partner may be the first to identify the problem. Obstructive sleep apnea is a common example of a sleep disorder that has implications in operational settings. There are many health consequences associated with sleep apnea, but, in addition, it has been shown to be associated with a twofold to sevenfold increase in risk for automobile accidents. 66,67Consistent with this, Powell et al . demonstrated that individuals with mild to moderate sleep apnea had a decrement in performance equivalent to that of an individual with a blood alcohol concentration of 0.05–0.08 g/dl. 68Alcohol is the most widely used sleep aid, and its use is typically intended to provide relaxation or to promote sleep. 69However, alcohol is a potent suppressor of rapid-eye-movement sleep, especially in the first half of the night. 70As the blood alcohol concentration declines, there is a rapid-eye-movement rebound in the second half of the night, producing more rapid-eye-movement sleep with increased awakenings and a reduction in total sleep time. Therefore, although alcohol may be consumed as an aid to promote sleep, it actually has the potential to significantly disrupt it.Sleep can be measured both subjectively, using a variety of questionnaires, and objectively, using standardized physiologic measures. Generally, humans are inaccurate subjective reporters of alertness. 71,72Individuals can report being awake and alert, when physiologically they could be asleep in minutes. This discrepancy between self or subjective reports and physiologic levels of alertness can have significant operational implications. First, it indicates that verbal reports of subjective alertness are to an individual's for an individual with the subjective and report of being be less likely to an alertness (e.g ., or as in the on alertness that could the physiologic is important to that when an individual reports a subjective at either of the (e.g ., fatigue or it is more likely to the physiologic human circadian is in the of the and is an for 24-h rhythms. most and of the is while a of the is by the at night and is by to the direct for and exposure to affect the circadian The daily the to its 24-h The tendency of the circadian clock is to than 24-h day, is the physiologic to than work–rest In other of shift from days to to nights has a circadian physiologic but this has not been a to the of shift work. a range of and For example, it the 24-h daily and as well as alertness and performance levels. the of sleep are important and complex but are the scope of this article and are are for increased sleepiness at two times and circadian associated with the levels of and performance and vulnerability to errors, incidents, and accidents, occurs at about an example, it has been well that a in fatigue-related accidents, alcohol occurs roughly between 3 and of alertness occur at approximately and to a different work such as the night shift or time the circadian will occur for days as the to the new environmental (e.g ., the after through several time work creates a different by its disruption of the circadian individuals are working at night, circadian sleep, and when they to sleep during the day, the circadian clock is for wakefulness. Generally, studies have shown that does not occur prolonged exposure to night work. an the individual and is to daytime that maintain for a factors such as with and that can only be during daytime hours also a role in the to the rhythm to night work. study of during anesthesia has for a circadian in clinical performance among risk of was greater at night to and among this investigation is of a negative circadian effect on performance, it was by the of as well as by not including important such as patient and physician data from of anesthesiologists other that fatigue is by as a significant risk for patients. In two studies of anesthesia more than reported having an in medical that they to fatigue. et al ., using the critical of anesthetic errors, estimated that human a role in more than of anesthetic and that fatigue was an associated factor in of reported critical a of New anesthesiologists, reported that they their limit for safe continuous of and reported having a fatigue-related from reports of critical to the from to revealed that fatigue was listed as a contributing factor in reports data suggest that there is a association between fatigue and errors at circadian The from these studies are they are on but the of that quality of care is compromised and that some errors are to working while recently the effect of fatigue in the was of falling asleep while an the was that the had been by about falling asleep during was of medical and of of and The was on a as the of on the had using of accident (table the of errors and accidents that occur in the are likely to have fatigue as a contributing factor on work schedules is a well-documented association between long work hours or late work and an increased potential for from accidents. The risk of an accident increases with hour after the consecutive hour of work. effect is exaggerated when work hours occur on a late shift. injuries, among the most frequent of the injuries by anesthesia are occur during or of and are associated with from fatigue. residents and medical there is a greater risk of a exposure during night work than during have the described risks associated with drowsy driving to physicians. physicians are at risk for accident and as they after their duty In a study of an of residents h of sleep while on reported falling asleep at the compared with of These residents had as many for than the in and emergency have been reported to the of accidents, in many cases while driving after being on call. a more recent study of risk among anesthesia only accidents were which not from the this to the circadian effect during the effect of work hours on pregnancy outcomes in resident physicians has been These data reveal that there is an increased incidence of pregnancy-induced hypertension, small-for-gestational-age infants. study an association between preterm delivery and residents who worked more than 100 h per in other “24/7” health care has some where fatigue was identified as causal or contributory. most often example is the of which attention on work hours and of resident physicians. there has been much to whether was related to the providers who for a high-profile was in that recommendations to limit house work hours and to increase their These recommendations of the of the New Health (table Accreditation Council on Graduate Medical and its and program requirements for resident duty hours, and work were required to that training program formal for resident duty hours that and care of patients. The for that duty hours not be and on average, residents have least day of 7 of and be on call in the hospital no more often than every if these are residents are from anesthesia on the day after evaluation suggests that the of resident duty hours may not be the that alone patient outcome. and after implementation of the New regulations found that there were no differences in mortality rate of patient to care or of and that there were more having at least one et al . demonstrated that adverse were more common when house were for compared with times when a resident the patient was with the care. follow-up study revealed that the quality of during patient the quality of care. suggests that during some use of residents to house may the of more medical errors, but that these errors be in other is among studies on the effects of fatigue on the performance of have the in most of the studies (table is not that the of this of data are these is a studies in the used for fatigue or sleep loss. studies of partial sleep deprivation reveal that performance decrements occur if sleep is by as as h, et al . used 4 h of sleep on the night prior to performance to between and is no for the that sleep times of greater than 4 h be considered as other use study conditions. of in studies is the of a standardized to performance. 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ABSTRACTWe examined the neural basis of emotion regulation in shift workers, and the relationships between the neural basis of emotion regulation, mood, sleep disturbance and 24‐h rest–activity rhythm (RAR). Fifty‐six shift workers (SW) with non‐standard shift schedules and 52 controls (CON) participated in this study. They completed self‐reported measures of sleep and mood problems, kept a sleep diary, and wore a wrist actigraphy device to assess sleep and 24‐h RAR. They underwent one‐night polysomnography and were scanned while performing an emotion regulation task. We examined group differences in the neural basis of emotion regulation and correlations between neural, mood, sleep and 24‐h RAR variables. SW showed greater sleep disturbance (i.e., lower actigraphy‐estimated sleep efficiency) and altered 24‐h RAR (e.g., lower actigraphy‐estimated interdaily stability) than CON. SW also exhibited increased anterior insula (AI) response to negative pictures (vs. neutral pictures) but reduced activation in the dorsomedial prefrontal cortex (dMPFC) and AI‐dMPFC functional connectivity during emotion regulation compared to CON. Shift work was associated with increased motor activity during the most active 10‐h period, which then contributed to increased AI response to negative pictures. Our findings suggest that shift work may be associated with the neurobiological alterations of emotion regulation. Furthermore, increased motor activity may serve as a pathway through which shift work could contribute to neurobiological alterations associated with emotional regulation.

Objective: This study aims to examine the levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) and brain volumes in shift-working men. Material and Methods: Forty-nine men who have been working in shifts for at least 1 year were included in the study. Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality, Montreal Cognitive Assessment (MoCA) test and trail making test (TMT) were used to assess cognitive performance, and Beck Anxiety Inventory (BAI) was used to assess anxiety level. Afterwards, plasma BDNF, GDNF and NT-3 levels were examined. Brain volume measurement was performed. Results: Since the PSQI results of shift-working men were above 5, it was determined that they had 'poor sleep quality'. According to the BAI results, 85% of them had anxiety. Primary-secondary school graduate shift-working men had lower MoCA value and TMT-A and TMT-B test scores were higher (p <0.05).Working in shifts for 6 years or more caused a significant decrease in BDNF and NT-3 levels (p<0.05). According to the correlation analysis results, it was observed that the prefrontal cortex, dorsolateral prefrontal cortex and cerebral cortex in the left lobe of the brain were smaller in elderly shift workers (p<0.05). Conclusion: There is a decrease in BDNF and NT-3 levels in shift workers of 6 years or more. Some brain regions associated with learning and memory have been found to be in smaller volumes in older shift workers.

Aim: Pilot study to examine the impact of shift work on cognitive function in Chinese coal mine workers. Background: Shift work is commonly used in modern industries such as the coal industry, and there is growing concern over the impact that shift work has on miners’ work performance and personal well-being. Method: A total of 54 miners working three shifts (17 in morning shift, 18 in afternoon, and 19 in night shift) participated in this exploratory study. A resting-state fNIRS functional connectivity method was conducted to assess the cognitive ability before and after the work shift. Results: Results showed significant differences in cognitive ability between before and after the work shifts among the three-shift workers. The brain functional connectivity was reduced ranking as the night, afternoon, and morning shifts. Decreased brain functional connectivity at the end of the working shift was found compared with before in the morning and afternoon shifts. Opposite results were obtained during the night shift. The resting-state functional brain networks in the prefrontal cortex of all groups exhibited small-world properties. Significant differences in betweenness centrality and nodal local efficiency were found in the prefrontal cortex in the morning and night shifts. Conclusions: The current findings provide new insights regarding the effect of shift work on the cognitive ability of Chinese coal mine workers from the view of brain science.

Introduction Shift work is known to be associated with sleep disturbance and circadian misalignment and may contribute to alterations in the brain implicated in emotion dysregulation. In this study, we examined 1) neural correlates of emotion dysregulation, including emotional reactivity and regulation in shift workers and 2) relationships between neural correlates of emotion dysregulation, sleep disturbance, and circadian misalignment. Methods Fifty-six rotating shift workers (SW, 42 females, 30.80 ± 6.94 years old) who had non-standard shift schedules and 52 healthy controls (HC, 36 females, 31.69 ± 7.86 years old) who did not work as shift schedules participated in this study. Both SW and HC completed self-reported measures of sleep and mood problems, and wrote sleep diary and wore actigraphy to assess sleep quality and circadian rhythms. They also underwent one night polysomnography and were scanned while they were performing the emotion regulation task. We analyzed group differences in mood, sleep, circadian rhythms, and neural bases of emotional reactivity and regulation, and examined relationships between these variables. Results SW showed significant differences in actigraphy-estimated sleep (i.e., lower sleep efficiency) and circadian rhythms (e.g., greater motor activity [M10] and lower interdaily stability) compared to HC. SW also exhibited increased anterior insula (AI) activation in response to negative pictures, but reduced activation in the dorsomedial prefrontal cortex (dMPFC) and AI-dMPFC functional connectivity during emotion regulation compared to HC. AI activation and AI-dMPFC functional connectivity were significantly associated with sleep disturbance (i.e., sleep diary-estimated sleep onset latency) and circadian misalignment (e.g., M10 and interdaily stability). Furthermore, a mediation analysis revealed that shift work was associated with increased motor activity during the most active 10-hour period, which then contributed to increased AI activation in response to negative pictures. Conclusion Our findings suggest that shift work may contribute to sleep disturbance and circadian misalignment, and neural alterations associated with emotional reactivity and regulation. Furthermore, the mediation result suggests that increased motor activity along with misaligned circadian rhythm may serve as a pathway, through shift work contributes to heightened emotional reactivity to negative information. Support (if any) National Research Foundation (No. 2022R1A2C2008417, NRF-2022R1A2C1008209) and Korea Institute for Advancement of Technology (No. 20009210).