This paper compares the statistical power of BOLD and arterial spin labeling perfusion fMRI for a variety of experimental designs within and across subjects. Based on theory and simulations, we predict that perfusion data are composed of independent observations in time under the null hypothesis, in contrast to BOLD data, which possess marked autocorrelation. We also present a method (sinc subtraction) of generating perfusion data from its raw source signal that minimizes the presence of oxygen-sensitive signal changes and can be used with any experimental design. Empirically, we demonstrate the absence of autocorrelation in perfusion noise, examine the shape of the hemodynamic response function for BOLD and perfusion, and obtain a measure of signal to noise for each method. This information is then used to generate a model of relative sensitivity of the BOLD and perfusion methods for within-subject experimental designs of varying temporal frequency. It is determined that perfusion fMRI provides superior sensitivity for within-subject experimental designs that concentrate their power at or below approximately 0.009 Hz (corresponding to a

STUDY OBJECTIVES: Although sleepiness appears to heighten distraction from the task at hand, especially if the latter is dull and monotonous, this aspect of sleep loss has not been assessed in any systematic way. Distractions are a potential cause of performance lapses (as are micro-sleeps). Here, we investigate the effects of sleepiness on a monotonous task, with and without distraction. DESIGN: Repeated Measures 2 x 2 counterbalanced design, comprising Sleepiness (night sleep restricted to 5 hours x normal sleep) and Distraction (distraction x no distraction). SETTING: Participants underwent 30-minute sessions on the Psychomotor Vigilance Test (2:00 PM - 3:10 PM), with or without an attractive distraction to be ignored, under normal and sleep-restricted conditions. PARTICIPANTS: Sixteen healthy young adults (mean age 21.10 years; 21-25 years [8 men; 8 women]) without any sleep or medical problems and without any indication of daytime sleepiness. INTERVENTIONS: Normal sleep versus sleep restricted to 5 hours and distraction versus no distraction. Distraction comprised a television in the visual periphery, showing an attractive video that had to be ignored. MEASUREMENTS AND RESULTS: Psychomotor Vigilance Test performance was monitored, as were the participants' head turns toward the television via videocameras. There was a significant increase in both head turns and lapses during sleep restriction plus distraction. Moreover, sleepiness also increased head turns even during no distraction. Distracting effects of sleepiness were clearly evident during the initial 10 minutes of testing. CONCLUSIONS: Distractibility is an important aspect of sleepiness, which has relevance to safety in the real world, eg, sleepy driving.

Here we report preliminary findings from a small-sample functional magnetic resonance imaging (fMRI) study of healthy adolescents who completed a working memory task in the context of a chronic sleep restriction experiment. Findings were consistent with those previously obtained on acutely sleep-deprived adults. Our data suggest that, when asked to maintain attention and burdened by chronic sleep restriction, the adolescent brain responds via compensatory mechanisms that accentuate the typical activation patterns of attention-relevant brain regions. Specifically, it appeared that regions that are normally active during an attention-demanding working memory task in the well-rested brain became even more active to maintain performance after chronic sleep restriction. In contrast, regions in which activity is normally suppressed during such a task in the well-rested brain showed even greater suppression to maintain performance after chronic sleep restriction. Although limited by the small sample, study results provide important evidence of feasibility, as well as guidance for future research into the functional neurological effects of chronic sleep restriction in general, the effects of sleep restriction in children and adolescents, and the neuroscience of attention and its disorders in children.

OBJECTIVE: To investigate if a fixed short sleep schedule impairs one of the main functions of sleep, which is to consolidate newly learned memories. METHODS: Sixteen young men participated in two experimental conditions, each of which lasted for 3 consecutive days and nights in our laboratory: a short sleep schedule (4.25-h sleep opportunity per night) versus a normal sleep schedule (8.5h per night). In the evening after two experimental nights, participants learned locations of 15 card pairs (spatial memory task) and a procedural finger tapping sequence task. Post-sleep retrieval of both memory tasks was tested the next morning. RESULTS: The short sleep schedule, compared with the normal sleep schedule, considerably altered sleep characteristics, e.g. the proportion of time in slow-wave sleep increased across the three experimental nights. In contrast, neither learning in the evening of day 2, nor subsequent overnight memory consolidation (i.e. concerning the change in memory performance between pre-sleep learning on day 2 and post-sleep retrieval on day 3) differed between the normal and short sleep schedule conditions. CONCLUSIONS: Our findings suggest that learning in the evening and subsequent sleep-dependent consolidation of procedural and spatial memories are unaltered in young men living under a fixed short sleep schedule. Future studies are warranted to validate our findings in other groups (e.g. adolescents and older subjects) and after more prolonged chronic sleep loss paradigms.

The neurobehavioral effects of 24 hr of total sleep deprivation (SD) on working memory in young healthy adults was studied using functional magnetic resonance imaging. Two tasks, one testing maintenance and the other manipulation and maintenance, were used. After SD, response times for both tasks were significantly slower. Performance was better preserved in the more complex task. Both tasks activated a bilateral, left hemisphere-dominant frontal-parietal network of brain regions reflecting the engagement of verbal working memory. In both states, manipulation elicited more extensive and bilateral (L>R) frontal, parietal, and thalamic activation. After SD, there was reduced blood oxygenation level-dependent signal response in the medial parietal region with both tasks. Reduced deactivation of the anterior medial frontal and posterior cingulate regions was observed with both tasks. Finally, there was disproportionately greater activation of the left dorsolateral prefrontal cortex and bilateral thalamus when manipulation was required. This pattern of changes in activation and deactivation bears similarity to that observed when healthy elderly adults perform similar tasks. Our data suggest that reduced activation and reduced deactivation could underlie cognitive impairment after SD and that increased prefrontal and thalamic activation may represent compensatory adaptations. The additional left frontal activation elicited after SD is postulated to be task dependent and contingent on task complexity. Our findings provide neural correlates to explain why task performance in relatively more complex tasks is better preserved relative to simpler ones after SD.

38 h of sleep deprivation in women resulted in decreased alpha, increased theta and increased intrahemispheric correlation during rest and increased theta and reaction time during task. F3-O1 coherent activity was selectively decreased consistent with the role of sleep for recovery of frontal functions. Sleep deprivation effects were milder in women than in men, however, recovery was not complete suggesting that women need more sleep than men to recover.

Waking brain physiology underlying deficits from continuous sleep restriction (CSR) is not well understood. Fourteen good sleepers participated in a 21-day protocol where they slept their usual amount in a baseline week, had their time in bed restricted by 33% in a CSR week, and slept the desired amount in a recovery week. Participants slept at home, completing diaries and wearing activity monitors to verify compliance. Each day participants completed an RT task and mood and sleepiness ratings every 3 h. Laboratory assessment of electrophysiology and performance took place at the end of baseline, three times throughout the CSR week, and at the beginning of recovery. Participants reported less sleep during CSR which was confirmed by activity monitors. Correspondingly, well-being and neurobehavioural performance was impaired. Quantitative EEG analysis revealed significantly reduced arousal between the 1st and 7th days of restriction and linear effects at anterior sites (Fp2, Fz, F8, T8). At posterior sites (P4, P8), reductions occurred only later in the week between the 4th and 7th nights of restriction. Both the immediate linear decline in arousal and precipitous drop later in the week were apparent at central sites (C4, Cz). Thus, frontal regions were affected immediately, while parietal regions showed maintenance of function until restriction was more severe. The P300 ERP component showed evidence of reduced attention by the 7th day of restriction (at Pz, P4). EEG and ERPs deficits were more robust in the right-hemisphere, which may reflect greater vulnerability to sleep loss in the non-dominant hemisphere.

Inadequate nightly sleep duration can impair daytime functioning, including interfering with attentional and other cognitive processes. Current models posit that attention is a complex function regulated by several separate, but interacting, neural systems responsible for vigilance, orienting, and executive control. However, it is not clear to what extent each of these underlying component processes is affected by sleep loss. The purpose of this study was to evaluate the effects of acute sleep restriction on these attentional components using the Dalhousie Computerized Attention Battery (DalCAB). DalCAB tasks were administered to healthy women (aged 19-25 years) on two consecutive mornings: once after a night with 9 h time in bed (TIB), and once again after either another night with 9 h TIB (control condition, n = 19) or after a night with 3 h TIB (sleep restriction condition, n = 20). Self-ratings of sleepiness and mood were also obtained following each sleep condition. Participants showed increases in self-reported sleepiness and fatigue after the second night only in the sleep restriction group. Sleep restriction primarily affected processing speed on tasks measuring vigilance; however, performance deficits were also observed on some measures of executive function (e.g., go/no-go task, flanker task, working memory). Tasks assessing orienting of attention were largely unaffected. These results indicate that acute sleep restriction has differential effects on distinct components of attention, which should be considered in modeling the impacts of sleep loss on the underlying attentional networks.

Adolescents are considered to be at risk for deteriorated cognitive functioning due to insufficient sleep. This systematic review examined the effects of experimental sleep manipulation on adolescent cognitive functioning. Sleep manipulations consisted of total or partial sleep restriction, sleep extension, and sleep improvement. Only articles written in English, with participants' mean age between 10 and 19 y, using objective sleep measures and cognitive performance as outcomes were included. Based on these criteria 16 articles were included. The results showed that the sleep manipulations were successful. Partial sleep restriction had small or no effects on adolescent cognitive functioning. Sleep deprivation studies showed decrements in the psychomotor vigilance task as most consistent finding. Sleep extension and sleep improvement contributed to improvement of working memory. Sleep directly after learning improved memory consolidation. Due to the great diversity of tests and lack of coherent results, decisive conclusions could not be drawn about which domains in particular were influenced by sleep manipulation. Small number of participants, not accounting for the role of sleep quality, individual differences in sleep need, compensatory mechanisms in adolescent sleep and cognitive functioning, and the impurity problem of cognitive tests might explain the absence of more distinct results.

Deficits in daytime performance due to sleep loss are experienced universally and associated with a significant social, financial, and human cost. Microsleeps, sleep attacks, and lapses in cognition increase with sleep loss as a function of state instability. Sleep deprivation studies repeatedly show a variable (negative) impact on mood, cognitive performance, and motor function due to an increasing sleep propensity and destabilization of the wake state. Specific neurocognitive domains including executive attention, working memory, and divergent higher cognitive functions are particularly vulnerable to sleep loss. In humans, functional metabolic and neurophysiological studies demonstrate that neural systems involved in executive function (i.e., prefrontal cortex) are more susceptible to sleep deprivation in some individuals than others. Recent chronic partial sleep deprivation experiments, which more closely replicate sleep loss in society, demonstrate that profound neurocognitive deficits accumulate over time in the face of subjective adaptation to the sensation of sleepiness. Sleep deprivation associated with disease-related sleep fragmentation (i.e., sleep apnea and restless legs syndrome) also results in neurocognitive performance decrements similar to those seen in sleep restriction studies. Performance deficits associated with sleep disorders are often viewed as a simple function of disease severity; however, recent experiments suggest that individual vulnerability to sleep loss may play a more critical role than previously thought.

This paper concerns temporal filtering in fMRI time-series analysis. Whitening serially correlated data is the most efficient approach to parameter estimation. However, if there is a discrepancy between the assumed and the actual correlations, whitening can render the analysis exquisitely sensitive to bias when estimating the standard error of the ensuing parameter estimates. This bias, although not expressed in terms of the estimated responses, has profound effects on any statistic used for inference. The special constraints of fMRI analysis ensure that there will always be a misspecification of the assumed serial correlations. One resolution of this problem is to filter the data to minimize bias, while maintaining a reasonable degree of efficiency. In this paper we present expressions for efficiency (of parameter estimation) and bias (in estimating standard error) in terms of assumed and actual correlation structures in the context of the general linear model. We show that: (i) Whitening strategies can result in profound bias and are therefore probably precluded in parametric fMRI data analyses. (ii) Band-pass filtering, and implicitly smoothing, has an important role in protecting against inferential bias.

Neuropsychological testing and brain imaging show that healthy aging leads to a preferential impairment of the prefrontal cortex (PFC). Interestingly, in young adults sleep deprivation (SD) has similar effects. Psychological tasks not so oriented to the PFC are less sensitive both to SD and aging. The PFC is a cortical region working particularly hard during wakefulness, which may make it more vulnerable to

Vigilant attention is a major component of a wide range of cognitive performance tasks. Vigilant attention is impaired by sleep deprivation and restored after rest breaks and (more enduringly) after sleep. The temporal dynamics of vigilant attention deficits across hours and days are driven by physiologic, sleep regulatory processes-a sleep homeostatic process and a circadian process. There is also evidence of a slower, allostatic process, which modulates the sleep homeostatic setpoint across days and weeks and is responsible for cumulative deficits in vigilant attention across consecutive days of sleep restriction. There are large inter-individual differences in vulnerability to sleep loss, and these inter-individual differences constitute a pronounced human phenotype. However, this phenotype is multi-dimensional; vulnerability in terms of vigilant attention impairment can be dissociated from vulnerability in terms of other cognitive processes such as attentional control. The vigilance decrement, or time-on-task effect-a decline in performance across the duration of a vigilant attention task-is characterized by progressively increasing response variability, which is exacerbated by sleep loss. This variability, while crucial to understanding the impact of sleep deprivation on performance in safety-critical tasks, is not well explained by top-down regulatory mechanisms, such as the homeostatic and circadian processes. A bottom-up, neuronal pathway-dependent mechanism involving use-dependent, local sleep may be the main driver of response variability. This bottom-up mechanism may also explain the dissociation between cognitive processes with regard to trait vulnerability to sleep loss.

OBJECTIVES: To test the feasibility of using a home-based sleep restriction protocol in adolescents and young adults; and to examine the different effects of chronic sleep restriction on a subjective sleepiness scale and working memory task in adolescents and young adults. METHOD: Twenty adolescents (ages 13-16 years) and 20 young adults (ages 18-20 years) underwent a 2-week home-based sleep manipulation protocol consisting of a week of 5 school days with 8 hr spent in bed per night and another week of 5 school days with 6 hr spent in bed per night. The protocol used a counterbalanced crossover experimental design. Subjective sleepiness was scored by the participant each morning, and working memory tests were administered during the weekend corresponding to each experimental week. RESULTS: Adherence to the prescribed protocol was similar in the two groups, and both groups achieved the desired differences in total sleep duration across the two sleep conditions. Subjective sleepiness scores significantly increased in young adults after sleep restriction, but were not accompanied by significant changes in working memory. However, reaction times during simple verbal and arithmetic working memory tasks increased among adolescents after sleep restriction, without affecting accuracy on task, and without eliciting increases in subjective sleepiness scores. CONCLUSION: Mild sleep restriction for 5 days impairs reaction times during working memory tasks in adolescents in the absence of increased perception of sleepiness.

Sleep deprivation is commonplace in modern society, but its far-reaching effects on cognitive performance are only beginning to be understood from a scientific perspective. While there is broad consensus that insufficient sleep leads to a general slowing of response speed and increased variability in performance, particularly for simple measures of alertness, attention and vigilance, there is much less agreement about the effects of sleep deprivation on many higher level cognitive capacities, including perception, memory and executive functions. Central to this debate has been the question of whether sleep deprivation affects nearly all cognitive capacities in a global manner through degraded alertness and attention, or whether sleep loss specifically impairs some aspects of cognition more than others. Neuroimaging evidence has implicated the prefrontal cortex as a brain region that may be particularly susceptible to the effects of sleep loss, but perplexingly, executive function tasks that putatively measure prefrontal functioning have yielded inconsistent findings within the context of sleep deprivation. Whereas many convergent and rule-based reasoning, decision making and planning tasks are relatively unaffected by sleep loss, more creative, divergent and innovative aspects of cognition do appear to be degraded by lack of sleep. Emerging evidence suggests that some aspects of higher level cognitive capacities remain degraded by sleep deprivation despite restoration of alertness and vigilance with stimulant countermeasures, suggesting that sleep loss may affect specific cognitive systems above and beyond the effects produced by global cognitive declines or impaired attentional processes. Finally, the role of emotion as a critical facet of cognition has received increasing attention in recent years and mounting evidence suggests that sleep deprivation may particularly affect cognitive systems that rely on emotional data. Thus, the extent to which sleep deprivation affects a particular cognitive process may depend on several factors, including the magnitude of global decline in general alertness and attention, the degree to which the specific cognitive function depends on emotion-processing networks, and the extent to which that cognitive process can draw upon associated cortical regions for compensatory support.

Maintaining attention for more than a few seconds is essential for mastering everyday life. Yet, our ability to stay focused on a particular task is limited, resulting in well-known performance decrements with increasing time on task. Intriguingly, such decrements are even more likely if the task is cognitively simple and repetitive. The attentional function that enables our prolonged engagement in intellectually unchallenging, uninteresting activities has been termed vigilant attention. Here we synthesized what we have learned from functional neuroimaging about the mechanisms of this essential mental faculty. To this end, a quantitative meta-analysis of pertinent neuroimaging studies was performed, including supplementary analyses of moderating factors. Furthermore, we reviewed the available evidence on neural time-on-task effects, additionally considering information obtained from patients with focal brain damage. Integrating the results of both meta-analysis and review, we identified a set of mainly right-lateralized brain regions that may form the core network subserving vigilant attention in humans, including dorsomedial, mid- and ventrolateral prefrontal cortex, anterior insula, parietal areas (intraparietal sulcus, temporoparietal junction), and subcortical structures (cerebellar vermis, thalamus, putamen, midbrain). We discuss the potential functional roles of different nodes of this network as well as implications of our findings for a theoretical account of vigilant attention. It is conjectured that sustaining attention is a multicomponent, nonunitary mental faculty, involving a mixture of (a) sustained/recurrent processes subserving task-set/arousal maintenance and (b) transient processes subserving the target-driven reorienting of attention. Finally, limitations of previous studies are considered and suggestions for future research are provided.

STUDY OBJECTIVES: To investigate the effects of sleep restriction (7 nights of 5 h time in bed [TIB]) on cognitive performance, subjective sleepiness, and mood in adolescents. METHODS: A parallel-group design was adopted in the Need for Sleep Study. Fifty-six healthy adolescents (25 males, age = 15-19 y) who studied in top high schools and were not habitual short sleepers were randomly assigned to Sleep Restriction (SR) or Control groups. Participants underwent a 2-w protocol consisting of 3 baseline nights (TIB = 9 h), 7 nights of sleep opportunity manipulation (TIB = 5 h for the SR and 9 h for the control groups), and 3 nights of recovery sleep (TIB = 9 h) at a boarding school. A cognitive test battery was administered three times each day. RESULTS: During the manipulation period, the SR group demonstrated incremental deterioration in sustained attention, working memory and executive function, increase in subjective sleepiness, and decrease in positive mood. Subjective sleepiness and sustained attention did not return to baseline levels even after 2 recovery nights. In contrast, the control group maintained baseline levels of cognitive performance, subjective sleepiness, and mood throughout the study. Incremental improvement in speed of processing, as a result of repeated testing and learning, was observed in the control group but was attenuated in the sleep-restricted participants, who, despite two recovery sleep episodes, continued to perform worse than the control participants. CONCLUSIONS: A week of partial sleep deprivation impairs a wide range of cognitive functions, subjective alertness, and mood even in high-performing high school adolescents. Some measures do not recover fully even after 2 nights of recovery sleep. COMMENTARY: A commentary on this article appears in this issue on page 497.

Cognitive and motor performance are critical in many circumstances and are impaired by sleep deprivation. We administered placebo, tyrosine 150 mg/kg, caffeine 300 mg/70 kg, phentermine 37.5 mg and D-amphetamine 20 mg at 15.30 h following overnight sleep deprivation and compare their effects on cognitive and motor performance in healthy young men. Tests of visual scanning, running memory, logical reasoning, mathematical processing, the Stroop task, four-choice serial reaction time, time wall take, pursuit tracking, visual vigilance, Trails (B) task and long-term memory were evaluated at standardized intervals before, during and after sleep deprivation and drugs. Performance decrements with sleep deprivation occurred in visual scanning, running memory, logical reasoning, mathematical processing, the Stroop test, the time wall test, tracking and visual vigilance. Interestingly, with sleep deprivation some tests improved and others did not deteriorate. Improvements with medication following sleep deprivation were seen in running memory, logical reasoning, mathematical processing, tracking and visual vigilance. Although less effective than D-amphetamine, tyrosine improved performance on several tests. We conclude that all drugs tested improved at least some aspects of cognitive and motor performance after sleep deprivation. As a naturally occurring amino acid, and thus amenable to nutritional strategies, tyrosine may deserve further testing.

STUDY OBJECTIVE: To examine whether differences in patterns of brain activation under baseline conditions relate to the differences in sleep-deprivation vulnerability. DESIGN: Using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging, we scanned 33 healthy young men while they performed the Sternberg working memory task following a normal night of sleep and again following 30 hours of sleep deprivation. From this initial group, based on their Sternberg working memory task performance, we found 10 subjects resilient to sleep deprivation (sleep deprivation-resilient group) and then selected 10 age- and education-matched subjects vulnerable to sleep deprivation (sleep deprivation-vulnerable group). SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Data from 10 young men (mean age 27.8 +/- 1.7 years) in the sleep deprivation-resilient group and 10 young men (mean age 28.2 +/- 1.9 years) in the sleep deprivation-vulnerable group were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We compared functional magnetic resonance imaging BOLD signal at rested baseline and sleep deprivation states in the 2 groups. As hypothesized, following sleep deprivation, both groups showed significant decreases in global brain activation compared to their rested group baseline. At rested baseline and in the sleep-deprivation state, the sleep deprivation-resilient group had significantly more brain activation than did the sleep deprivation-vulnerable group. There were also differences in functional circuits within and between groups in response to sleep deprivation. CONCLUSIONS: These preliminary data suggest that patterns of brain activation during the Sternberg working memory task at the rested baseline and the sleep-deprivation state, differ across individuals as a function of their sleep-deprivation vulnerability.

Vigilance is a term with varied definitions but the most common usage is sustained attention or tonic alertness. This usage of vigilance implies both the degree of arousal on the sleep-wake axis and the level of cognitive performance. There are many interacting neural and neurotransmitter systems that affect vigilance. Most studies of vigilance have relied on states where the sleep-wake state is altered, e.g. drowsiness, sleep-deprivation, and CNS-active drugs, but there are factors ranging from psychophysics to motivation that may impact vigilance. While EEG is the most commonly studied physiologic measure of vigilance, various measures of eye movement and of autonomic nervous system activity have also been used. This review paper discusses the underlying neural basis of vigilance and its assessment using physiologic tools. Since, assessment of vigilance requires assessment of cognitive function this aspect is also discussed.

BACKGROUND: Perfusion functional magnetic resonance imaging (fMRI) was used to investigate the effect of genetic variation of the human serotonin transporter (5-HTT) gene (5-HTTLPR, SLC6A4) on resting brain function of healthy individuals. METHODS: Twenty-six healthy subjects, half homozygous for the 5-HTTLPR short allele (s/s group) and half homozygous for the long allele (l/l group), underwent perfusion functional and structural magnetic resonance imaging during a resting state. The two genotype groups had no psychiatric illness and were similar in age, gender, and personality scores. RESULTS: Compared with the l/l group, the s/s group showed significantly increased resting cerebral blood flow (CBF) in the amygdala and decreased CBF in the ventromedial prefrontal cortex. The effect of functional modulation in these regions by 5-HTTLPR genotype cannot be accounted for by variations in brain anatomy, personality, or self-reported mood. CONCLUSIONS: The 5-HTTLPR genotype alters resting brain function in emotion-related regions in healthy individuals, including the amygdala and ventromedial prefrontal cortex. Such alterations suggest a broad role of the 5-HTT gene in brain function that may be associated with the genetic susceptibility for mood disorders such as depression.

Functional MRI (fMRI) has begun to be used to explore human brain activity during ecological and natural conditions. Arterial spin labeling (ASL) perfusion fMRI provides an appealing approach for imaging sustained brain activity during natural conditions because of its long-term temporal stability and ability to noninvasively quantify absolute cerebral blood flow (CBF). The present study used ASL perfusion fMRI to measure brain activation patterns associated with natural vision by concurrently recording CBF and blood oxygen level-dependent (BOLD) contrasts while subjects were freely viewing a cartoon movie. Reliable quantitative whole-brain CBF values ( approximately 60 mL/100g/min) as well as regional CBF values (45 approximately 80 mL/100g/min) were measured during movie viewing and resting states. The perfusion contrast revealed CBF increases in multiple visual pathway areas and frontal areas, and CBF decreases in ventromedial frontal cortex and superior temporal cortex during movie viewing compared to resting states. Concurrent BOLD contrast revealed similar but weaker activation and deactivation patterns. Regression analyses of both CBF data and BOLD data showed significant associations between activation in the middle temporal (MT) region and subjects' perception of motion. Region of interest analysis based on a priori literature-defined MT demonstrated significant monotonic stepwise associations between the intensity of motion perception and the CBF and BOLD signal changes. These results demonstrate the feasibility of using ASL perfusion fMRI for imaging both sustained and dynamic effects in neural activation during natural and ecologically valid situations, and support the notion of maintained functional segregation and specialization during natural vision.

The aim of the present study was to investigate how three nights of sleep restriction affected cognitive functions in young and aged healthy women. Ten young (20-30 years) and ten aged (55-65 years) women participated to the study. After one baseline night (11 pm-07 am), their sleep was restricted to 4h per night (01-05 am) during three nights. A recovery night of 8h (11 pm-07 am) followed the sleep restriction. The neurobehavioural assessment included evaluation of Attention (Stroop, Trail Making test, Tests of Attentional Performance), Memory (Buschke, Logical Memory, PASAT, Brown Peterson), Addition of numbers and Abstraction (Wisconsin). Sleep restriction decreased significantly the speed of execution, particularly in the young women, without affecting the accuracy of the answers. This effect was the most significant on reaction times in simple tests. The more complex tasks (PASAT, Brown Peterson, Logical Memory, Addition of numbers, Wisconsin) were not affected. However, the inhibition of an automatic activity (Stroop test) and the formation of a memory trace (Buschke memory test) were disturbed in both young and older women.

PURPOSE OF REVIEW: This review investigates the potential bi-directional relation between sleep and diet in considering their contribution to cardiovascular health. We further explore the involvement of the gut microbiome in the relationships between poor sleep and dietary intakes and increased cardiovascular disease (CVD) risk. RECENT FINDINGS: There is strong evidence that sleep restriction leads to unhealthy food choices and increased energy intake. The diet may impact sleep, as well. Epidemiological studies show that higher adherence to a Mediterranean dietary pattern predicts healthier sleep. One factor that could underlie these relationships is the gut microbiome. Although data are mixed, there is some evidence that sleep restriction can influence the composition of the gut microbiome in humans. Similarly, Mediterranean diets and other plant-rich diets are related to increased diversity of the microbiota. At present, few studies have investigated the influence of the microbiome on sleep; however, limited evidence from epidemiological and intervention studies suggest that the composition of the microbiome may relate to sleep quality. More research is needed to better understand the role of the microbiome in the multi-directional relationship between sleep, diet, and CVD. There is growing evidence of a bi-directional relationship between sleep and the diet, which could act in concert to influence CVD risk. Diets such as the Mediterranean diet, comprised of high intakes of fruits, vegetables, and other plant-based foods, may promote healthy sleep and beneficial gut microflora. The gut microbiome may then underlie the relation between diet, sleep, and CVD risk.

The effects of a 3-week computerised alertness training on chronic (>3 months) visuospatial hemineglect were investigated prospectively in seven patients by means of neuropsychological tests and functional magnetic resonance imaging (fMRI). Following the alertness training, the group showed improved alertness and a significant improvement in the performance of a neglect test battery over and above any improvement during a 3-week baseline phase. Improvements in the neglect tasks were accompanied by an increase of right hemisphere neural activity in frontal cortex, anterior cingulate cortex, precuneus, cuneus and angular gyrus. These areas have previously been associated with alertness and spatial attention. A similar pattern of increased neural activity was found for the left hemisphere. Four weeks after the end of the training, the patients' neglect test performance had mostly returned to baseline, while the increases in neural activity bilaterally in frontal areas, in the right anterior cingulate cortex, the right angular gyrus and the left temporoparietal cortex remained. The data show that a 3-week computerised alertness training can improve performance both in alertness and neglect tests and that these behavioural improvements are associated with reactivation in areas associated with alerting and visuospatial attention. The limited stability of these effects over time suggests that a 3-week alertness training alone does not result in long lasting improvements in every patient, but refining the treatment protocol may lead to a more stable amelioration of neglect symptoms.

Inadequate sleep impairs cognitive function and has been associated with worse academic achievement in higher education students; however, studies that control for relevant background factors and include knowledge on sleep hygiene are scarce. This study examined the association of chronic sleep reduction (i.e. symptoms of chronic sleep reduction such as shortness of sleep, sleepiness and irritation), subjective sleep quality and sleep hygiene knowledge with academic achievement (grades and study credits) and study concentration among 1378 higher education students (71% female, mean age 21.73 years, SD = 3.22) in the Netherlands. Demographic, health, lifestyle and study behaviour characteristics were included as covariates in hierarchical regression analyses. After controlling for significant covariates, only chronic sleep reduction remained a significant predictor of lower grades (last exam, average in current academic year). Better sleep quality and sleep hygiene knowledge were associated with better academic achievement, but significance was lost after controlling for covariates, except for a remaining positive association between sleep hygiene beliefs and grades in the current academic year. Moreover, better sleep quality and lower scores on chronic sleep reduction were associated with better study concentration after controlling for significant covariates. To conclude, chronic sleep reduction is associated with academic achievement and study concentration in higher education students. Inadequate sleep hygiene knowledge is moderately associated with worse academic achievement. Future research should investigate whether sleep hygiene interventions improve academic achievement in students of higher education.

Sleep before learning benefits memory encoding through unknown mechanisms. We found that even a mild sleep disruption that suppressed slow-wave activity and induced shallow sleep, but did not reduce total sleep time, was sufficient to affect subsequent successful encoding-related hippocampal activation and memory performance in healthy human subjects. Implicit learning was not affected. Our results suggest that the hippocampus is particularly sensitive to shallow, but intact, sleep.

The importance of sufficient sleep for cognitive performance has been increasingly recognized. Individual differences in susceptibility to effects of sleep restriction have hardly been investigated in children. We investigated whether individual differences in temperament moderate the association of sleep duration with sustained attention, inhibition, and working memory in 123 children (42% boys) aged 9 to 11 years. Sleep duration was assessed using parental diaries, and temperament traits of extraversion and negative affectivity were assessed by child self-report (Early Adolescent Temperament Questionnaire-Revised). Computerized assessment of sustained attention (short-form Psychomotor Vigilance Task, PVT), inhibition (PVT Go/No-Go adaptation), and working memory (visual Digit Span) were performed at school. Our findings demonstrate that long-sleeping introverted and negatively affective children show worse sustained attention and working memory than short-sleeping children with these temperaments.

OBJECTIVES: There is broad evidence that sleep as opposed to waking facilitates the consolidation of both declarative and procedural memory. The current study addressed the question whether different extents of sleep restriction after learning would impair long-term memory consolidation in adolescents. METHODS: Eighty-eight healthy adolescents were randomized to five different sleep protocols with 9, 8, 7, 6 or 5 h of time in bed for four consecutive nights under controlled conditions that excluded daytime sleep. Declarative (word-pair task) and procedural memory (mirror tracing task) encoding was assessed prior to the sleep restriction protocol. Recall was assessed after two recovery nights following the sleep protocol and 4 weeks later. RESULTS: Sleep diaries and actigraphy data demonstrated that the participants closely followed the sleep protocols. There were no differences in demographic parameters or memory encoding at baseline. In contrast to the initial prediction, restriction of nocturnal sleep over four consecutive nights had no significant impact on declarative or procedural memory consolidation. Polysomnographic monitoring after sleep restriction demonstrated a high preservation of the amount of slow wave sleep in the restricted conditions. CONCLUSIONS: The results suggest that adolescents show a high resilience of memory consolidation to substantial sleep curtailment across four nights that might be promoted by increased sleep intensity under conditions of sleep restriction.

Functional magnetic resonance imaging (fMRI) has become the most widely used modality for visualizing regional brain activation in response to sensorimotor or cognitive tasks. While the majority of fMRI studies have used blood oxygenation level-dependent (BOLD) contrast as a marker for neural activation, baseline drift effects result in poor sensitivity for detecting slow variations in neural activity. By contrast, drift effects are minimized in arterial spin labeling (ASL) perfusion contrast, primarily as a result of successive pairwise subtraction between images acquired with and without labeling. Recent data suggest that ASL contrast shows stable noise characteristics over the entire frequency spectrum, which makes it suitable for studying low-frequency events in brain function. The present study investigates the relative sensitivities of ASL and BOLD contrast in detecting changes in motor cortex activation over a spectrum of frequencies of experimental design, where the alternating period between the resting state and activation is varied from 30 s up to 24 hr. The results demonstrate that 1) ASL contrast can detect differences in motor cortex activation over periods of minutes, hours, and even days; 2) the functional sensitivity of ASL contrast becomes superior to that of BOLD contrast when the alternating period between the resting state and activation is greater than a few minutes; and 3) task activation measured by ASL tends to have less intersubject variability than BOLD contrast. The improved sensitivity of the ASL contrast for low task frequency and longitudinal studies, along with its superior power in group analysis, is expected to extend the range of experimental designs that can be studied using fMRI.

The influence of menstrual cycle phase and oral contraceptive use on neurobehavioral function and circadian rhythms were studied in healthy young women (n = 25) using a modified constant routine procedure during 24 h of sleep deprivation. Alertness and performance worsened across sleep deprivation and also varied with circadian phase. Entrained circadian rhythms of melatonin and body temperature were evident in women regardless of menstrual phase or oral contraceptive use. No significant difference in melatonin levels, duration, or phase was observed between women in the luteal and follicular phases, whereas oral contraceptives appeared to increase melatonin levels. Temperature levels were higher in the luteal phase and in oral contraceptive users compared to women in the follicular phase. Alertness on the maintenance of wakefulness test and some tests of cognitive performance were poorest for women in the follicular phase especially near the circadian trough of body temperature. These observations suggest that hormonal changes associated with the menstrual cycle and the use of oral contraceptives contribute to changes in nighttime waking neurobehavioral function and temperature level whereas these factors do not appear to affect circadian phase.

BACKGROUND: Sleep is increasingly recognized as a potential risk for overweight and obesity. Observational studies have shown links between short sleep duration with weight gain. However, the findings from longitudinal studies in adults are conflicting. This review aimed to examine the effectiveness of experimental sleep restriction on adult body weight. METHOD: A systematic search was undertaken in MEDLINE, EMBASE, PsycINFO, and CENTRAL (Cochrane center register of controlled trials) to identify experimental studies examining the effectiveness of sleep restriction on body weight, and search period was from January 2005 to June 2018. Meta-analysis was applied by using the random model. RESULTS: A total of 275 adults from six experimental studies were included. The pooled standard mean difference in body weight and body fat was 0.44 (95% CI - 0.13 to 1.02) (Z = 1.51, p > 0.05) and 0.35 kg (95% CI - 0.19 to 0.88) (Z = 1.27, p > 0.05), respectively. The experimental sleep restriction did not result in significant differences in adult body weight or body fat. Subgroup analysis showed that there were differences in weight gain between genders and races. CONCLUSION: The finding from this review cannot support the hypothesis from observational studies that short sleep leads to weight gain.

Working memory (WM) components are altered after total sleep deprivation (TSD), both with respect to information replacement and result judgment. However, the electrophysiological mechanisms of WM alterations following sleep restriction remain largely unknown. To identify such mechanisms, event-related potentials were recorded during the n-back WM task, before and after 36 h sleep deprivation. Thirty-one young volunteers participated in this study and performed a two-back WM task with simultaneous electroencephalography (EEG) recording before and after TSD and after 8 h time in bed for recovery (TIBR). Repeated measures analysis of variance revealed that, compared to resting wakefulness, sleep deprivation induced a decrease in the P200 amplitude and induced longer reaction times. ERP-component scalp topographies results indicated that such decrease primarily occurred in the frontal cortex. The N200 and P300 amplitudes also decreased after TSD. Our results suggest that decreased information replacement of WM occurs after 36 h of TSD and that 8 h TIBR after a long period of TSD leads to partial restoration of WM functions. The present findings represent the EEG profile of WM during mental fatigue.

More than a third of US adults report fewer than 6 hours of sleep a night, making chronic sleep restriction a growing public health concern. Sleep curtailment is associated with an increase in industrial accidents, motor vehicle accidents, medical and other occupational errors. Young adults are more vulnerable to acute sleep deprivation than older adults, but less is known about how young vs. older adults respond to the more commonly experienced chronic sleep restriction. To test the hypothesis that young adults are more vulnerable to chronic sleep loss than older adults, we compared data from young and older adults who underwent three weeks of chronic sleep restriction (equivalent to 5.6 hours/24 hours) combined with recurrent circadian disruption in an experiment that enabled us to separate the influences of the sleep-wake homeostatic process, the circadian timing system, and the chronic sleep deficit. We found that while young and older adults reported similar levels of subjective sleepiness, objective measures of sleepiness revealed that young adults were more vulnerable and had more attentional failures than the older adults. These results have important public health implications, particularly related to prevention of sleep-related motor vehicle crashes in young drivers. Further research is needed to understand the neurobiological basis of these age-related differences.