Impact of one night of sleep restriction on sleepiness and cognitive function: A systematic review and meta-analysis.

Detrimental consequences of chronic sleep restriction on cognitive function are well established in the literature. However, effects of a single night of sleep restriction remain equivocal. Therefore, we synthesized data from 44 studies to investigate effects of sleep restriction to 2-6 h sleep opportunity on sleepiness and cognition in this meta-analysis. We investigated subjective sleepiness, sustained attention, choice reaction time, cognitive throughput, working memory, and inhibitory control. Results revealed a significant increase in subjective sleepiness following one night of sleep restriction (Standardized Mean Difference (SMD) = 0.986, p < 0.001), while subjective sleepiness was not associated with sleep duration during sleep restriction (ß = -0.214, p = 0.039, significance level 0.01). Sustained attention, assessed via common 10-min tasks, was impaired, as demonstrated through increased reaction times (SMD = 0.512, p < 0.001) and attentional lapses (SMD = 0.489, p < 0.001). However, the degree of impaired attention was not associated with sleep duration (ps > 0.090). We did not find significant effects on choice reaction time, cognitive throughput, working memory, or inhibitory control. Overall, results suggest that a single night of restricted sleep can increase subjective sleepiness and impair sustained attention, a cognitive function crucial for everyday tasks such as driving.

Aging effects on the encoding/retrieval flip in associative memory: fMRI evidence from incidental contingency learning.

Introduction: Associative memory is arguably the most basic memory function and therein constitutes the foundation of all episodic and semantic memory processes. At the same time, the decline of associative memory represents a core feature of age-related cognitive decline in both, healthy and pathological (i.e., dementia-related) aging. The neural mechanisms underlying age-related impairments in associative memory are still not fully understood, especially regarding incidental (i.e., non-intentional) learning. Methods: We investigated the impact of age on the incidental learning and memory retrieval of face-name combinations in a total sample of 46 young (N = 23; mean age = 23.39 years) and elderly (N = 22, mean age = 69.05 years) participants. More specifically, particular interest was placed in age-related changes in encoding/retrieval (E/R) flips, which denote a neural antagonism of opposed activation patterns in the same brain region during memory encoding and retrieval, which were assessed using fMRI. Results: According to our hypothesis, the results showed a significant age-related decline in the retrieval performance in the old group. Additionally, at the neural level, we discovered an abolished E/R flip in the right anterior insula and a joint but reduced E/R flip activation magnitude in the posterior middle cingulate cortex in older subjects. Discussion: In conclusion, the present findings suggest that the impaired neural modulation of the E/R flip in the right aIC might be a sensitive marker in the early detection of neural aging.

Association between circadian sleep regulation and cortical gyrification in young and older adults.

The circadian system orchestrates sleep timing and structure and is altered with increasing age. Sleep propensity, and particularly REM sleep is under strong circadian control and has been suggested to play an important role in brain plasticity. In this exploratory study, we assessed whether surface-based brain morphometry indices are associated with circadian sleep regulation and whether this link changes with age. Twenty-nine healthy older (55-82 years; 16 men) and 28 young participants (20-32 years; 13 men) underwent both structural magnetic resonance imaging and a 40-h multiple nap protocol to extract sleep parameters over day and night time. Cortical thickness and gyrification indices were estimated from T1-weighted images acquired during a classical waking day. We observed that REM sleep was significantly modulated over the 24-h cycle in both age groups, with older adults exhibiting an overall reduction in REM sleep modulation compared to young individuals. Interestingly, when taking into account the observed overall age-related reduction in REM sleep throughout the circadian cycle, higher day-night differences in REM sleep were associated with increased cortical gyrification in the right inferior frontal and paracentral regions in older adults. Our results suggest that a more distinctive allocation of REM sleep over the 24-h cycle is associated with regional cortical gyrification in aging, and thereby point towards a protective role of circadian REM sleep regulation for age-related changes in brain organization.

Regular Caffeine Intake Delays REM Sleep Promotion and Attenuates Sleep Quality in Healthy Men.

Acute caffeine intake can attenuate homeostatic sleep pressure and worsen sleep quality. Caffeine intake-particularly in high doses and close to bedtime-may also affect circadian-regulated rapid eye movement (REM) sleep promotion, an important determinant of subjective sleep quality. However, it is not known whether such changes persist under chronic caffeine consumption during daytime. Twenty male caffeine consumers (26.4 ± 4 years old, habitual caffeine intake 478.1 ± 102.8 mg/day) participated in a double-blind crossover study. Each volunteer completed a caffeine (3 × 150 mg caffeine daily for 10 days), a withdrawal (3 × 150 mg caffeine for 8 days then placebo), and a placebo condition. After 10 days of controlled intake and a fixed sleep-wake cycle, we recorded electroencephalography for 8 h starting 5 h after habitual bedtime (i.e., start on average at 04:22 h which is around the peak of circadian REM sleep promotion). A 60-min evening nap preceded each sleep episode and reduced high sleep pressure levels. While total sleep time and sleep architecture did not significantly differ between the three conditions, REM sleep latency was longer after daily caffeine intake compared with both placebo and withdrawal. Moreover, the accumulation of REM sleep proportion was delayed, and volunteers reported more difficulties with awakening after sleep and feeling more tired upon wake-up in the caffeine condition compared with placebo. Our data indicate that besides acute intake, also regular daytime caffeine intake affects REM sleep regulation in men, such that it delays circadian REM sleep promotion when compared with placebo. Moreover, the observed caffeine-induced deterioration in the quality of awakening may suggest a potential motive to reinstate caffeine intake after sleep.

The impact of daily caffeine intake on nighttime sleep in young adult men.

Acute caffeine intake can delay sleep initiation and reduce sleep intensity, particularly when consumed in the evening. However, it is not clear whether these sleep disturbances disappear when caffeine is continuously consumed during daytime, which is common for most coffee drinkers. To address this question, we investigated the sleep of twenty male young habitual caffeine consumers during a double-blind, randomized, crossover study including three 10-day conditions: caffeine (3 × 150 mg caffeine daily), withdrawal (3 × 150 mg caffeine for 8 days, then switch to placebo), and placebo (3 × placebo daily). After 9 days of continuous treatment, electroencephalographically (EEG)-derived sleep structure and intensity were recorded during a scheduled 8-h nighttime sleep episode starting 8 (caffeine condition) and 15 h (withdrawal condition) after the last caffeine intake. Upon scheduled wake-up time, subjective sleep quality and caffeine withdrawal symptoms were assessed. Unexpectedly, neither polysomnography-derived total sleep time, sleep latency, sleep architecture nor subjective sleep quality differed among placebo, caffeine, and withdrawal conditions. Nevertheless, EEG power density in the sigma frequencies (12-16 Hz) during non-rapid eye movement sleep was reduced in both caffeine and withdrawal conditions when compared to placebo. These results indicate that daily caffeine intake in the morning and afternoon hours does not strongly impair nighttime sleep structure nor subjective sleep quality in healthy good sleepers who regularly consume caffeine. The reduced EEG power density in the sigma range might represent early signs of overnight withdrawal from the continuous presence of the stimulant during the day.

Intraocular cataract lens replacement and light exposure potentially impact procedural learning in older adults.

Procedural learning declines with age and appropriately timed light exposure can improve cognitive performance in older individuals. Because cataract reduces light transmission and is associated with cognitive decline in older adults, we explored whether lens replacement (intraocular blue-blocking [BB] or UV-only blocking) in older patients with cataracts enhances the beneficial effects of light on procedural learning. Healthy older participants (n = 16) and older patients with post-cataract surgery (n = 13 with BB or UV lens replacement) underwent a randomized within-subject crossover laboratory design with three protocols. In each protocol, 3.5 hr dim-dark adaptation was followed by 2 hr evening blue-enriched (6,500K) or non-blue-enriched light exposure (3,000K or 2,500K), 30 min dim post-light, ~8 hr sleep and 2 hr morning dim light. Procedural learning was assessed by the alternating serial reaction time task (ASRT), as part of a larger test battery. Here, ASRT performance was indexed by type of trial (random or sequence) and sequence-specific (high or low probability) measures. During evening light exposure, we observed a significant effect of the interaction of "group" versus "light condition" on the type of trial (p = .04; p = .16; unadjusted and adjusted p-values, respectively) and sequence-specific learning (p = .04; p = .16; unadjusted and adjusted p-values, respectively), whereby patients with UV lens replacement performed better than patients with BB lens or non-cataract controls, during blue-enriched light exposure. Lens replacement in patients with cataracts may potentially be associated with beneficial effects of blue light on procedural learning. Thus, optimizing spectral lens transmission in patients with cataracts may help improve specific aspects of cognitive function, such as procedural learning.

Time to Recover From Daily Caffeine Intake.

Caffeine elicits widespread effects in the central nervous system and is the most frequently consumed psychostimulant worldwide. First evidence indicates that, during daily intake, the elimination of caffeine may slow down, and the primary metabolite, paraxanthine, may accumulate. The neural impact of such adaptions is virtually unexplored. In this report, we leveraged the data of a laboratory study with N = 20 participants and three within-subject conditions: caffeine (150 mg caffeine × 3/day × 10 days), placebo (150 mg mannitol × 3/day × 10 days), and acute caffeine deprivation (caffeine × 9 days, afterward placebo × 1 day). On day 10, we determined the course of salivary caffeine and paraxanthine using liquid chromatography-mass spectrometry coupled with tandem mass spectrometry. We assessed gray matter (GM) intensity and cerebral blood flow (CBF) after acute caffeine deprivation as compared to changes in the caffeine condition from our previous report. The results indicated that levels of paraxanthine and caffeine remained high and were carried overnight during daily intake, and that the levels of paraxanthine remained elevated after 24 h of caffeine deprivation compared to placebo. After 36 h of caffeine deprivation, the previously reported caffeine-induced GM reduction was partially mitigated, while CBF was elevated compared to placebo. Our findings unveil that conventional daily caffeine intake does not provide sufficient time to clear up psychoactive compounds and restore cerebral responses, even after 36 h of abstinence. They also suggest investigating the consequences of a paraxanthine accumulation during daily caffeine intake.

Wide awake at bedtime? Effects of caffeine on sleep and circadian timing in male adolescents - A randomized crossover trial.

Adolescents often suffer from short and mistimed sleep. To counteract the resulting daytime sleepiness they frequently consume caffeine. However, caffeine intake may exaggerate sleep problems by disturbing sleep and circadian timing. In a 28-hour double-blind randomized crossover study, we investigated to what extent caffeine disturbs slow-wave sleep (SWS) and delays circadian timing in teenagers. Following a 6-day ambulatory phase of caffeine abstinence and fixed sleep-wake cycles, 18 male teenagers (14-17 years old) ingested 80 mg caffeine vs. placebo in the laboratory four hours prior to an electro-encephalographically (EEG) recorded nighttime sleep episode. Data were analyzed using both frequentist and Bayesian statistics. The analyses suggest that subjective sleepiness is reduced after caffeine compared to placebo. However, we did not observe a strong caffeine-induced reduction in subjective sleep quality or SWS, but rather a high inter-individual variability in caffeine-induced SWS changes. Exploratory analyses suggest that particularly those individuals with a higher level of SWS during placebo reduced SWS in response to caffeine. Regarding salivary melatonin onsets, caffeine-induced delays were not evident at group level, and only observed in participants exposed to a higher caffeine dose relative to individual bodyweight (i.e., a dose > 1.3 mg/kg). Together, the results suggest that 80 mg caffeine are sufficient to induce alertness at a subjective level. However, particularly teenagers with a strong need for deep sleep might pay for these subjective benefits by a loss of SWS during the night. Thus, caffeine-induced sleep-disruptions might change along with the maturation of sleep need.

Correlation Between Hippocampal Volume and Autobiographical Memory Depending on Retrieval Frequency in Healthy Individuals and Patients with Alzheimer's Disease.

The hippocampus plays an indispensable role in episodic memory, particularly during the consolidation process. However, its precise role in retrieval of episodic memory is still ambiguous. In this study, we investigated the correlation of hippocampal morphometry and the performance in an autobiographical memory task in 27 healthy controls and 24 patients suffering from Alzheimer's disease (AD). Most importantly, correlations were defined separately and comparatively for memory contents with different retrieval frequency in the past. In healthy subjects, memory performance for seldom retrieved autobiographical events was significantly associated with gray matter density in the bilateral hippocampus, whereas this correlation was not present for events with high retrieval frequency. This pattern of findings confirms that retrieval frequency plays a critical role in the consolidation of episodic autobiographical memories, thereby making them more independent of the hippocampal system. In AD patients, on the other hand, successful memory retrieval appeared to be related to hippocampal morphometry irrespective of the contents' retrieval frequency, comprising events with high retrieval frequency, too. The observed differences between patients and control subjects suggest that AD-related neurodegeneration not only impairs the function, but also decreases the functional specialization of the hippocampal memory system, which, thus, may be considered as marker for AD.

Author Correction: Human brain patterns underlying vigilant attention: impact of sleep debt, circadian phase and attentional engagement.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Neural Mechanisms of Associative Memory Revisited: fMRI Evidence from Implicit Contingency Learning.

The literature describes a basic neurofunctional antagonism between episodic memory encoding and retrieval with opposed patterns of neural activation and deactivation, particularly in posterior midline regions. This has been coined the encoding/retrieval (E/R) flip. The present fMRI study uses an innovative task paradigm to further elucidate neurofunctional relations of encoding and retrieval in associative memory. Thereby, memory encoding is implemented as implicit (non-deliberate) cognitive process, whereas the prior literature focused mainly on explicit encoding. Moreover, instead of defining brain activations related to successful (vs. unsuccessful) memory performance, the task paradigm provides proper no-memory baseline conditions. More specifically, the encoding task includes trials with non-contingent (not learnable) stimulus combinations, while the retrieval task uses trials with a simple matching exercise with no mnemonic requirements. The analyses revealed circumscribed activation in the posterior middle cingulate cortex (pMCC) together with prominent deactivation in the anterior insula cortex (aIC) as core neural substrate of implicit memory encoding. Thereby, the pMCC exhibited positive functional connectivity to the hippocampus. Memory retrieval was related to an activation pattern exactly opposed to memory encoding with deactivation in the pMCC and activation in the aIC, while the aIC additionally exhibited a negative (i.e., arguably inhibitive) functional connectivity to the pMCC. Important to note, the observed pattern of activations/de-activations in the pMCC appears to conflict with prevalent E/R flip findings. The outlined results and their (alleged) discrepancies with prior study reports are discussed primarily in the context of the default mode network's functioning and its context-sensitive regulation. Finally, we point out the relevance of the present work for the understanding and further investigation of the neurofunctional aberrations occurring during normal and pathological aging.

Human brain patterns underlying vigilant attention: impact of sleep debt, circadian phase and attentional engagement.

Sleepiness and cognitive function vary over the 24-h day due to circadian and sleep-wake-dependent mechanisms. However, the underlying cerebral hallmarks associated with these variations remain to be fully established. Using functional magnetic resonance imaging (fMRI), we investigated brain responses associated with circadian and homeostatic sleep-wake-driven dynamics of subjective sleepiness throughout day and night. Healthy volunteers regularly performed a psychomotor vigilance task (PVT) in the MR-scanner during a 40-h sleep deprivation (high sleep pressure) and a 40-h multiple nap protocol (low sleep pressure). When sleep deprived, arousal-promoting thalamic activation during optimal PVT performance paralleled the time course of subjective sleepiness with peaks at night and troughs on the subsequent day. Conversely, task-related cortical activation decreased when sleepiness increased as a consequence of higher sleep debt. Under low sleep pressure, we did not observe any significant temporal association between PVT-related brain activation and subjective sleepiness. Thus, a circadian modulation in brain correlates of vigilant attention was only detectable under high sleep pressure conditions. Our data indicate that circadian and sleep homeostatic processes impact on vigilant attention via specific mechanisms; mirrored in a decline of cortical resources under high sleep pressure, opposed by a subcortical "rescuing" at adverse circadian times.

Differential impact in young and older individuals of blue-enriched white light on circadian physiology and alertness during sustained wakefulness.

We tested the effect of different lights as a countermeasure against sleep-loss decrements in alertness, melatonin and cortisol profile, skin temperature and wrist motor activity in healthy young and older volunteers under extendend wakefulness. 26 young [mean (SE): 25.0 (0.6) y)] and 12 older participants [(mean (SE): 63.6 (1.3) y)] underwent 40-h of sustained wakefulness during 3 balanced crossover segments, once under dim light (DL: 8 lx), and once under either white light (WL: 250 lx, 2,800 K) or blue-enriched white light (BL: 250 lx, 9,000 K) exposure. Subjective sleepiness, melatonin and cortisol were assessed hourly. Skin temperature and wrist motor activity were continuously recorded. WL and BL induced an alerting response in both the older (p = 0.005) and the young participants (p = 0.021). The evening rise in melatonin was attentuated under both WL and BL only in the young. Cortisol levels were increased and activity levels decreased in the older compared to the young only under BL (p = 0.0003). Compared to the young, both proximal and distal skin temperatures were lower in older participants under all lighting conditions. Thus the color temperature of normal intensity lighting may have differential effects on circadian physiology in young and older individuals.

Cognitive brain responses during circadian wake-promotion: evidence for sleep-pressure-dependent hypothalamic activations.

The two-process model of sleep-wake regulation posits that sleep-wake-dependent homeostatic processes interact with the circadian timing system to affect human behavior. The circadian timing system is fundamental to maintaining stable cognitive performance, as it counteracts growing homeostatic sleep pressure during daytime. Using magnetic resonance imaging, we explored brain responses underlying working memory performance during the time of maximal circadian wake-promotion under varying sleep pressure conditions. Circadian wake-promoting strength was derived from the ability to sleep during an evening nap. Hypothalamic BOLD activity was positively linked to circadian wake-promoting strength under normal, but not under disproportionally high or low sleep pressure levels. Furthermore, higher hypothalamic activity under normal sleep pressure levels predicted better performance under sleep loss. Our results reappraise the two-process model by revealing a homeostatic-dose-dependent association between circadian wake-promotion and cognition-related hypothalamic activity.

Pushing the Limits: Chronotype and Time of Day Modulate Working Memory-Dependent Cerebral Activity.

Morning-type individuals experience more difficulties to maintain optimal attentional performance throughout a normal waking day than evening types. However, time-of-day modulations may differ across cognitive domains. Using functional magnetic resonance imaging (fMRI), we investigated how chronotype and time of day interact with working memory at different levels of cognitive load/complexity in a N-back paradigm (N0-, N2-, and N3-back levels). Extreme morning- and evening-type individuals underwent two fMRI sessions during N-back performance, one 1.5 h (morning) and one 10.5 h (evening) after wake-up time scheduled according to their habitual sleep-wake preference. At the behavioral level, increasing working memory load resulted in lower accuracy while chronotype and time of day only exerted a marginal impact on performance. Analyses of neuroimaging data disclosed an interaction between chronotype, time of day, and the modulation of cerebral activity by working memory load in the thalamus and in the middle frontal cortex. In the subjective evening hours, evening types exhibited higher thalamic activity than morning types at the highest working memory load condition only (N3-back). Conversely, morning-type individuals exhibited higher activity than evening-type participants in the middle frontal gyrus during the morning session in the N3-back condition. Our data emphasize interindividual differences in time-of-day preferences and underlying cerebral activity, which should be taken into account when investigating vigilance state effects in task-related brain activity. These results support the hypothesis that higher task complexity leads to a chronotype-dependent increase in thalamic and frontal brain activity, permitting stabilization of working memory performance across the day.

Dawn simulation light impacts on different cognitive domains under sleep restriction.

Chronic sleep restriction (SR) has deleterious effects on cognitive performance that can be counteracted by light exposure. However, it is still unknown if naturalistic light settings (dawn simulating light) can enhance daytime cognitive performance in a sustainable matter. Seventeen participants were enrolled in a 24-h balanced cross-over study, subsequent to SR (6-h of sleep). Two different light settings were administered each morning: a) dawn simulating light (DsL; polychromatic light gradually increasing from 0 to 250 lx during 30 min before wake-up time, with light around 250 lx for 20 min after wake-up time) and b) control dim light (DL; <8 lx). Cognitive tests were performed every 2 h during scheduled wakefulness and questionnaires were completed hourly to assess subjective mood. The analyses yielded a main effect of "light condition" for the motor tracking task, sustained attention to response task and a working memory task (visual 1 and 3-back task), as well as for the Simple Reaction Time Task, such that participants showed better task performance throughout the day after morning DsL exposure compared to DL. Furthermore, low performers benefited more from the light effects compared to high performers. Conversely, no significant influences from the DsL were found for the Psychomotor Vigilance Task and a contrary effect was observed for the digit symbol substitution test. No light effects were observed for subjective perception of sleepiness, mental effort, concentration and motivation. Our data indicate that short exposure to artificial morning light may significantly enhance cognitive performance in a domain-specific manner under conditions of mild SR.

The circadian regulation of sleep: impact of a functional ADA-polymorphism and its association to working memory improvements.

Sleep is regulated in a time-of-day dependent manner and profits working memory. However, the impact of the circadian timing system as well as contributions of specific sleep properties to this beneficial effect remains largely unexplored. Moreover, it is unclear to which extent inter-individual differences in sleep-wake regulation depend on circadian phase and modulate the association between sleep and working memory. Here, sleep electroencephalography (EEG) was recorded during a 40-h multiple nap protocol, and working memory performance was assessed by the n-back task 10 times before and after each scheduled nap sleep episode. Twenty-four participants were genotyped regarding a functional polymorphism in adenosine deaminase (rs73598374, 12 G/A-, 12 G/G-allele carriers), previously associated with differences in sleep-wake regulation. Our results indicate that genotype-driven differences in sleep depend on circadian phase: heterozygous participants were awake longer and slept less at the end of the biological day, while they exhibited longer non rapid eye movement (NREM) sleep and slow wave sleep concomitant with reduced power between 8-16 Hz at the end of the biological night. Slow wave sleep and NREM sleep delta EEG activity covaried positively with overall working memory performance, independent of circadian phase and genotype. Moreover, REM sleep duration benefitted working memory particularly when occurring in the early morning hours and specifically in heterozygous individuals. Even though based on a small sample size and thus requiring replication, our results suggest genotype-dependent differences in circadian sleep regulation. They further indicate that REM sleep, being under strong circadian control, boosts working memory performance according to genotype in a time-of-day dependent manner. Finally, our data provide first evidence that slow wave sleep and NREM sleep delta activity, majorly regulated by sleep homeostatic mechanisms, is linked to working memory independent of the timing of the sleep episode within the 24-h cycle.

Light modulation of human sleep depends on a polymorphism in the clock gene Period3.

Non-image-forming (NIF) responses to light powerfully modulate human physiology. However, it remains scarcely understood how NIF responses to light modulate human sleep and its EEG hallmarks, and if there are differences across individuals. Here we investigated NIF responses to light on sleep in individuals genotyped for the PERIOD3 (PER3) variable-number tandem-repeat (VNTR) polymorphism. Eighteen healthy young men (20-28 years; mean ± SEM: 25.9 ± 1.2) homozygous for the PER3 polymorphism were matched by age, body-mass index, and ethnicity. The study protocol comprised a balanced cross-over design during the winter, during which participants were exposed to either light of 40 lx at 6,500 K (blue-enriched) or light at 2,500 K (non-blue enriched), during 2h in the evening. Compared to light at 2,500 K, light at 6,500 K induced a significant increase in all-night NREM sleep slow-wave activity (SWA: 1.0-4.5 Hz) in the occipital cortex for PER3(5/5) individuals, but not for PER3(4/4) volunteers. Dynamics of SWA across sleep cycles revealed increased occipital NREM sleep SWA for virtually all sleep episode only for PER3(5/5) individuals. Furthermore, they experienced light at 6,500 K as significantly brighter. Intriguingly, this subjective perception of brightness significantly predicted their increased occipital SWA throughout the sleep episode. Our data indicate that humans homozygous for the PER3(5/5) allele are more sensitive to NIF light effects, as indexed by specific changes in sleep EEG activity. Ultimately, individual differences in NIF light responses on sleep may depend on a clock gene polymorphism involved in sleep-wake regulation.

Insights into behavioral vulnerability to differential sleep pressure and circadian phase from a functional ADA polymorphism.

Sleep loss affects human behavior in a nonuniform manner, depending on the cognitive domain and also the circadian phase. Besides, evidence exists about stable interindividual variations in sleep loss-related performance impairments. Despite this evidence, only a few studies have considered both circadian phase and neurobehavioral domain when investigating trait-like vulnerability to sleep manipulation. By applying a randomized, crossover design with 2 sleep pressure conditions (40 h sleep deprivation vs. 40 h multiple naps), we investigated the influence of a human adenosine deaminase (ADA) polymorphism (rs73598374) on several behavioral measures throughout nearly 2 circadian cycles. Confirming earlier studies, we observed that under sleep deprivation the previously reported vulnerable G/A-allele carriers felt overall sleepier than G/G-allele carriers. As expected, this difference was no longer present when sleep pressure was reduced by the application of multiple naps. Concomitantly, well-being was worse in the G/A genotype under sleep loss when compared to the nap protocol, and n-back working memory performance appeared to be specifically susceptible to sleep-wake manipulation in this genotype. When considering psychomotor vigilance performance, however, a higher sensitivity to sleep-wake manipulation was detected in homozygous participants, but specifically at the end of the night and only for optimal task performance. Although these data are based on a small sample size and hence require replication (12 G/A- and 12 G/G-allele carriers), they confirm the assumption that interindividual differences regarding the effect of sleep manipulation highly depend on the cognitive task and circadian phase, and thus emphasize the necessity of a multimethodological approach. Moreover, they indicate that napping might be suitable to counteract endogenously heightened sleep pressure depending on the neurobehavioral domain.

Time-on-task decrement in vigilance is modulated by inter-individual vulnerability to homeostatic sleep pressure manipulation.

Under sleep loss, vigilance is reduced and attentional failures emerge progressively. It becomes difficult to maintain stable performance over time, leading to growing performance variability (i.e., state instability) in an individual and among subjects. Task duration plays a major role in the maintenance of stable vigilance levels, such that the longer the task, the more likely state instability will be observed. Vulnerability to sleep-loss-dependent performance decrements is highly individual and is also modulated by a polymorphism in the human clock gene PERIOD3 (PER3). By combining two different protocols, we manipulated sleep-wake history by once extending wakefulness for 40 h (high sleep pressure condition) and once by imposing a short sleep-wake cycle by alternating 160 min of wakefulness and 80 min naps (low sleep pressure condition) in a within-subject design. We observed that homozygous carriers of the long repeat allele of PER3 (PER3 (5/5) ) experienced a greater time-on-task dependent performance decrement (i.e., a steeper increase in the number of lapses) in the Psychomotor Vigilance Task compared to the carriers of the short repeat allele (PER3 (4/4) ). These genotype-dependent effects disappeared under low sleep pressure conditions, and neither motivation, nor perceived effort accounted for these differences. Our data thus suggest that greater sleep-loss related attentional vulnerability based on the PER3 polymorphism is mirrored by a greater state instability under extended wakefulness in the short compared to the long allele carriers. Our results undermine the importance of time-on-task related aspects when investigating inter-individual differences in sleep loss-induced behavioral vulnerability.