Impact of menstrual cycle phase and oral contraceptives on sleep and overnight memory consolidation.

Sleep spindles benefit declarative memory consolidation and are considered to be a biological marker for general cognitive abilities. However, the impact of sexual hormones and hormonal oral contraceptives (OCs) on these relationships are less clear. Thus, we here investigated the influence of endogenous progesterone levels of naturally cycling women and women using OCs on nocturnal sleep and overnight memory consolidation. Nineteen healthy women using OCs (MAge  = 21.4, SD = 2.1 years) were compared to 43 healthy women with a natural menstrual cycle (follicular phase: n = 16, MAge  = 21.4, SD = 3.1 years; luteal phase: n = 27, MAge  = 22.5, SD = 3.6 years). Sleep spindle density and salivary progesterone were measured during an adaptation and an experimental night. A word pair association task preceding the experimental night followed by two recalls (pre-sleep and post-sleep) was performed to test declarative memory performance. We found that memory performance improved overnight in all women. Interestingly, women using OCs (characterized by a low endogenous progesterone level but with very potent synthetic progestins) and naturally cycling women during the luteal phase (characterized by a high endogenous progesterone level) had a higher fast sleep spindle density compared to naturally cycling women during the follicular phase (characterized by a low endogenous progesterone level). Furthermore, we observed a positive correlation between endogenous progesterone level and fast spindle density in women during the luteal phase. Results suggest that the use of OCs and the menstrual cycle phase affects sleep spindles and therefore should be considered in further studies investigating sleep spindles and cognitive performance.

Gross motor adaptation benefits from sleep after training.

Sleep has been shown to facilitate the consolidation of newly acquired motor memories. However, the role of sleep in gross motor learning, especially in motor adaptation, is less clear. Thus, we investigated the effects of nocturnal sleep on the performance of a gross motor adaptation task, i.e. riding an inverse steering bicycle. Twenty-six male participants (M = 24.19, SD = 3.70 years) were randomly assigned to a PM-AM-PM (n = 13) or an AM-PM-AM (n = 13) group, i.e. they trained in the evening/morning and were re-tested the next morning/evening and the following evening/morning (PM-AM-PM/AM-PM-AM group) so that every participant spent one sleep as well as one wake interval between the three test sessions. Inverse cycling performance was assessed by speed (riding time) and accuracy (standard deviation of steering angle) measures. Behavioural results showed that in the PM-AM-PM group a night of sleep right after training stabilized performance (accuracy and speed) and was further improved over the subsequent wake interval. In the AM-PM-AM group, a significant performance deterioration after the initial wake interval was followed by the restoration of subjects' performance levels from right after training when a full night of sleep was granted. Regarding sleep, right hemispheric fast N2 sleep spindle activity was related to better stabilization of inverse cycling skills, thus possibly reflecting the ongoing process of updating the participants' mental model from "how to ride a bicycle" to "how to ride an inverse steering bicycle". Our results demonstrate that sleep facilitates the consolidation of gross motor adaptation, thus adding further insights to the role of sleep for tasks with real-life relevance.

Procedural memory consolidation is associated with heart rate variability and sleep spindles.

Sleep and memory studies often focus on overnight rather than long-term memory changes, traditionally associating overnight memory change (OMC) with sleep architecture and sleep patterns such as spindles. In addition, (para-)sympathetic innervation has been associated with OMC after a daytime nap using heart rate variability (HRV). In this study we investigated overnight and long-term performance changes for procedural memory and evaluated associations with sleep architecture, spindle activity (SpA) and HRV measures (R-R interval [RRI], standard deviation of R-R intervals [SDNN], as well as spectral power for low [LF] and high frequencies [HF]). All participants (N = 20, Mage  = 23.40 ± 2.78 years) were trained on a mirror-tracing task and completed a control (normal vision) and learning (mirrored vision) condition. Performance was evaluated after training (R1), after a full-night sleep (R2) and 7 days thereafter (R3). Overnight changes (R2-R1) indicated significantly higher accuracy after sleep, whereas a significant long-term (R3-R2) improvement was only observed for tracing speed. Sleep architecture measures were not associated with OMC after correcting for multiple comparisons. However, individual SpA change from the control to the learning night indicated that only "SpA enhancers" exhibited overnight improvements for accuracy and long-term improvements for speed. HRV analyses revealed that lower SDNN and LF power was associated with better OMC for the procedural speed measure. Altogether, this study indicates that overnight improvement for procedural memory is specific for spindle enhancers, and is associated with HRV during sleep following procedural learning.

Short sleep-poor sleep? A polysomnographic study in a large population-based sample of women.

There is a lack of studies on the association between total sleep time (TST) and other polysomnographical parameters. A key question is whether a short sleep is an expression of habitual short sleep, or whether it reflects temporary impairment. The purpose of the present study was to investigate the association between TST and amount of sleep stages and sleep continuity measures, in a large population-based sample of women (n = 385), sleeping at home in a normal daily life setting. The results show that sleep efficiency, N1 (min), N2 (min), REM (min), REM% and proportion of long sleep segments, increased with increasing TST, whereas the number of awakenings/hr, the number of arousals/hr, N1% and REM intensity decreased. In addition, longer sleep was more associated with TST being perceived as of "usual" duration and with better subjective sleep quality. TST was not associated with habitual reported sleep duration. It was concluded that short TST of a recorded sleep in a real-life context may be an indicator of poor objective sleep quality for that particular sleep episode. Because individuals clearly perceived this reduction, it appears that self-reports of poor sleep quality often may be seen as indicators of poor sleep quality. It is also concluded that PSG-recorded sleep duration does not reflect habitual reported sleep duration in the present real-life context.

The impact of sleep on complex gross-motor adaptation in adolescents.

Sleep has been shown to facilitate the consolidation of newly acquired motor memories in adults. However, the role of sleep in motor memory consolidation is less clear in children and adolescents, especially concerning real-life gross-motor skills. Therefore, we investigated the effects of sleep and wakefulness on a complex gross-motor adaptation task by using a bicycle with an inverse steering device. A total of 29 healthy adolescents aged between 11 and 14 years (five female) were either trained to ride an inverse steering bicycle (learning condition) or a stationary bicycle (control condition). Training took place in the morning (wake, n = 14) or in the evening (sleep, n = 15) followed by a 9-hr retention interval and a subsequent re-test session. Slalom cycling performance was assessed by speed (riding time) and accuracy (standard deviation of steering angle) measures. Behavioural results showed no evidence for sleep-dependent memory consolidation. However, overnight gains in accuracy were associated with an increase in left hemispheric N2 slow sleep spindle activity from control to learning night. Furthermore, decreases in REM and tonic REM duration were related to higher overnight improvements in accuracy. Regarding speed, an increase in REM and tonic REM duration was favourable for higher overnight gains in riding time. Thus, although not yet detectable on a behavioural level, sleep seemed to play a role in the acquisition of gross-motor skills. A promising direction for future research is to focus on the possibility of delayed performance gains in adolescent populations.

The effect of daytime napping and full-night sleep on the consolidation of declarative and procedural information.

Many studies investigating sleep and memory consolidation have evaluated full-night sleep rather than alternative sleep periods such as daytime naps. This multi-centre study followed up on, and was compared with, an earlier full-night study (Schabus et al., 2004) investigating the relevance of daytime naps for the consolidation of declarative and procedural memory. Seventy-six participants were randomly assigned to a nap or wake group, and performed a declarative word-pair association or procedural mirror-tracing task. Performance changes from before to after a 90-min retention interval filled with sleep or quiet wakefulness were evaluated between groups. Associations between performance changes, sleep architecture, spindles, and slow oscillations were investigated. For the declarative task we observed a trend towards stronger forgetting across a wake period compared with a nap period, and a trend towards memory increase over the full-night. For the procedural task, accuracy was significantly decreased following daytime wakefulness, showed a trend to increase with a daytime nap, and significantly increased across full-night sleep. For the nap protocol, neither sleep stages, spindles, nor slow oscillations predicted performance changes. A direct comparison of day and nighttime sleep revealed that daytime naps are characterized by significantly lower spindle density, but higher spindle activity and amplitude compared with full-night sleep. In summary, data indicate that daytime naps protect procedural memories from deterioration, whereas full-night sleep improves performance. Given behavioural and physiological differences between day and nighttime sleep, future studies should try to characterize potential differential effects of full-night and daytime sleep with regard to sleep-dependent memory consolidation.

Developmental changes of sleep spindles and their impact on sleep-dependent memory consolidation and general cognitive abilities: A longitudinal approach.

Sleep spindles are related to sleep-dependent memory consolidation and general cognitive abilities. However, they undergo drastic maturational changes during adolescence. Here we used a longitudinal approach (across 7 years) to explore whether developmental changes in sleep spindle density can explain individual differences in sleep-dependent memory consolidation and general cognitive abilities. Ambulatory polysomnography was recorded during four nights in 34 healthy subjects (24 female) with two nights (baseline and experimental) at initial recording (age range 8-11 years) and two nights at follow-up recording (age range 14-18 years). For declarative learning, participants encoded word pairs with a subsequent recall before and after sleep. General cognitive abilities were measured by the Wechsler Intelligence Scale. Higher slow (11-13 Hz) than fast (13-15 Hz) spindle density at frontal, central, and parietal sites during initial recordings, followed by a shift to higher fast than slow spindle density at central and parietal sites during follow-up recordings, suggest that mature spindle topography develops throughout adolescence. Fast spindle density increases from baseline to experimental night were positively related to sleep-dependent memory consolidation. In addition, we found that the development of fast spindles predicted the improvement in memory consolidation across the two longitudinal measurements, a finding that underlines a crucial role for mature fast spindles for sleep-dependent memory consolidation. Furthermore, slow spindle changes across adolescence were related to general cognitive abilities, a relationship that could indicate the maturation of frontal networks relevant for efficient cognitive processing. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=7NXJzm8HbIw and https://www.youtube.com/watch?v=iuMQY1OIJ0s.

Age affects sleep microstructure more than sleep macrostructure.

It is well known that the quantity and quality of physiological sleep changes across age. However, so far the effect of age on sleep microstructure has been mostly addressed in small samples. The current study examines the effect of age on several measures of sleep macro- and microstructure in 211 women (22-71 years old) of the 'Sleep and Health in Women' study for whom ambulatory polysomnography was registered. Older age was associated with significantly lower fast spindle (effect size f2  = 0.32) and K-complex density (f2  = 0.19) during N2 sleep, as well as slow-wave activity (log) in N3 sleep (f2  = 0.21). Moreover, total sleep time (f2  = 0.10), N3 sleep (min) (f2  = 0.10), rapid eye movement sleep (min) (f2  = 0.11) and sigma (log) (f2  = 0.05) and slow-wave activity (log) during non-rapid eye movement sleep (f2  = 0.09) were reduced, and N1 sleep (f2  = 0.03) was increased in older age. No significant effects of age were observed on slow spindle density, rapid eye movement density and beta power (log) during non-rapid eye movement sleep. In conclusion, effect sizes indicate that traditional sleep stage scoring may underestimate age-related changes in sleep.

The relation between polysomnography and subjective sleep and its dependence on age - poor sleep may become good sleep.

Women complain more about sleep than men, but polysomnography (PSG) seems to suggest worse sleep in men. This raises the question of how women (or men) perceive objective (PSG) sleep. The present study sought to investigate the relation between morning subjective sleep quality and PSG variables in older and younger women. A representative sample of 251 women was analysed in age groups above and below 51.5 years (median). PSG was recorded at home during one night. Perceived poor sleep was related to short total sleep time (TST), long wake within total sleep time (WTSP), low sleep efficiency and a high number of awakenings. The older women showed lower TST and sleep efficiency and higher WTSP for a rating of good sleep than did the younger women. For these PSG variables the values for good sleep in the older group were similar to the values for poor sleep in the young group. It was concluded that women perceive different levels of sleep duration, sleep efficiency and wake after sleep onset relatively well, but that older women adjust their objective criteria for good sleep downwards. It was also concluded that age is an important factor in the relation between subjective and objective sleep.

Oscillatory theta activity during memory formation and its impact on overnight consolidation: a missing link?

Sleep has been shown to promote memory consolidation driven by certain oscillatory patterns, such as sleep spindles. However, sleep does not consolidate all newly encoded information uniformly but rather "selects" certain memories for consolidation. It is assumed that such selection depends on salience tags attached to the new memories before sleep. However, little is known about the underlying neuronal processes reflecting presleep memory tagging. The current study sought to address the question of whether event-related changes in spectral theta power (theta ERSP) during presleep memory formation could reflect memory tagging that influences subsequent consolidation during sleep. Twenty-four participants memorized 160 word pairs before sleep; in a separate laboratory visit, they performed a nonlearning control task. Memory performance was tested twice, directly before and after 8 hr of sleep. Results indicate that participants who improved their memory performance overnight displayed stronger theta ERSP during the memory task in comparison with the control task. They also displayed stronger memory task-related increases in fast sleep spindle activity. Furthermore, presleep theta activity was directly linked to fast sleep spindle activity, indicating that processes during memory formation might indeed reflect memory tagging that influences subsequent consolidation during sleep. Interestingly, our results further indicate that the suggested relation between sleep spindles and overnight performance change is not as direct as once believed. Rather, it appears to be mediated by processes beginning during presleep memory formation. We conclude that theta ERSP during presleep memory formation reflects cortico-hippocampal interactions that lead to a better long-term accessibility by tagging memories for sleep spindle-related reprocessing.

Effects of evening smartphone use on sleep and declarative memory consolidation in male adolescents and young adults.

Exposure to short-wavelength light before bedtime is known to disrupt nocturnal melatonin secretion and can impair subsequent sleep. However, while it has been demonstrated that older adults are less affected by short-wavelength light, there is limited research exploring differences between adolescents and young adults. Furthermore, it remains unclear whether the effects of evening short-wavelength light on sleep architecture extend to sleep-related processes, such as declarative memory consolidation. Here, we recorded polysomnography from 33 male adolescents (15.42 ± 0.97 years) and 35 male young adults (21.51 ± 2.06 years) in a within-subject design during three different nights to investigate the impact of reading for 90 min either on a smartphone with or without a blue-light filter or from a printed book. We measured subjective sleepiness, melatonin secretion, sleep physiology and sleep-dependent memory consolidation. While subjective sleepiness remained unaffected, we observed a significant melatonin attenuation effect in both age groups immediately after reading on the smartphone without a blue-light filter. Interestingly, adolescents fully recovered from the melatonin attenuation in the following 50 min before bedtime, whereas adults still, at bedtime, exhibited significantly reduced melatonin levels. Sleep-dependent memory consolidation and the coupling between sleep spindles and slow oscillations were not affected by short-wavelength light in both age groups. Nevertheless, adults showed a reduction in N3 sleep during the first night quarter. In summary, avoiding smartphone use in the last hour before bedtime is advisable for adolescents and young adults to prevent sleep disturbances. Our research empirically supports general sleep hygiene advice and can inform future recommendations regarding the use of smartphones and other screen-based devices before bedtime.

Immunogenicity Parameters of Cancer Patients Receiving the mRNA Vaccine BNT162b2 While Obtaining Radiotherapy: A Longitudinal Cohort Evaluation.

BACKGROUND: Cancer patients are highly prone to infectious diseases. While undergoing antineoplastic treatment, the risk of severe symptoms upon infection increases, necessitating efficient protective measures, such as vaccination. For patients receiving radiotherapy, there is no specific information about humoral immunity. During the COVID-19 pandemic, serial antibody measurements were therefore offered to cancer patients, following SARS-CoV-2 vaccination while obtaining radiotherapy. METHODS: Out of 74 enrolled patients, 46 met the inclusion criteria. Two cohorts were allocated, depending on an association with chemotherapy or pure radiotherapy. An additional healthy control cohort of 16 healthcare workers was enrolled. All participants followed a two-fold BNT162b2 vaccine schedule. SARS-CoV-2 binding antibodies were measured serially in a 7-day cycle for 35 days and over the long-term, using the Elecsys® Anti-SARS-CoV-2 immunoassay. RESULTS: Cancer patients under pure radiotherapy have a comparable humoral vaccination response and long-term persistency of antibodies to healthy controls. Patients receiving additional chemotherapy show a significantly delayed immune response and decreased antibody titers. The vaccine was well tolerated in all cohorts. CONCLUSIONS: Pure radiotherapy in cancer patients does not interfere with the vaccine-induced humoral immune response or other immunogenetic aspects, whereas previous or simultaneous chemotherapy does. Findings are of particular relevance for future epidemic or pandemic scenarios.

SARS-CoV-2 vaccination willingness and humoral vaccination response in radiation oncology patients.

BACKGROUND: SARS-CoV-2 infection has been and, in some parts, still is a threat to oncologic patients, making it crucial to understand perception of vaccination and immunologic responses in this vulnerable patient segment. SARS-CoV-2 vaccines in relation to malignant disease characteristics and therapies have so far not been studied consecutively in larger oncologic patient populations. This study captures SARS-CoV-2 vaccination willingness and humoral immune response in a large consecutive oncologic patient collective at the beginning of 2021. METHODS: 1142 patients were consecutively recruited over 5.5 months at a tertiary department for radiation oncology and were assessed for vaccination willingness via a standardized interview. In already vaccinated patients total SARS-CoV-2 S antibody titres against the spike protein (Anti-SARS-CoV-2 S) and were evaluated 35 days or later after the first dose of SARS-CoV-2 vaccine. RESULTS: Vaccination willingness was high with a rate of 90 %. The most frequent reasons for rejection were: undecided/potential vaccination after therapy, distrust in the vaccine and fear of interaction with comorbidities. Factors associated with lower vaccination willingness were: worse general condition, lower age and female sex. 80 % of the participants had been previously vaccinated, 8 % reported previous infection and 16 % received vaccination during antineoplastic therapy. In 97.5 % of the vaccinated patients Anti-SARS-CoV-2 S was detected. In a univariable analysis parameters associated with non-conversion were: lower performance status, spread to the local lymphatics (N + ), hematologic disease and diffuse metastases. All patients with oligometastatic disease achieved positive Anti-SARS-CoV-2 S titres. For patients with two vaccinations several risk factors were identified, that were associated with low antibody concentrations. CONCLUSIONS: SARS-CoV-2 vaccination willingness among oncologic patients was high in the first months after its availability, and most patients had already received one or two doses. Over 97 % of vaccinated patients had measurable anti-SARS-CoV-2 S titres. Our data supports early identification of low humoral responders after vaccination and could facilitate the design of future oncologic vaccine trials (clinicaltrials.gov Identifier: NCT04918888).

Guidelines for the recording and evaluation of pharmaco-sleep studies in man: the International Pharmaco-EEG Society (IPEG).

The International Pharmaco-EEG Society (IPEG) presents guidelines summarising the requirements for the recording and computerised evaluation of pharmaco-sleep data in man. Over the past years, technical and data-processing methods have advanced steadily, thus enhancing data quality and expanding the palette of sleep assessment tools that can be used to investigate the activity of drugs on the central nervous system (CNS), determine the time course of effects and pharmacodynamic properties of novel therapeutics, hence enabling the study of the pharmacokinetic/pharmacodynamic relationship, and evaluate the CNS penetration or toxicity of compounds. However, despite the presence of robust guidelines on the scoring of polysomnography -recordings, a review of the literature reveals inconsistent -aspects in the operating procedures from one study to another. While this fact does not invalidate results, the lack of standardisation constitutes a regrettable shortcoming, especially in the context of drug development programmes. The present guidelines are intended to assist investigators, who are using pharmaco-sleep measures in clinical research, in an effort to provide clear and concise recommendations and thereby to standardise methodology and facilitate comparability of data across laboratories.

Sleep spindle maturity promotes slow oscillation-spindle coupling across child and adolescent development.

The synchronization of canonical fast sleep spindle activity (12.5-16 Hz, adult-like) precisely during the slow oscillation (0.5-1 Hz) up peak is considered an essential feature of adult non-rapid eye movement sleep. However, there is little knowledge on how this well-known coalescence between slow oscillations and sleep spindles develops. Leveraging individualized detection of single events, we first provide a detailed cross-sectional characterization of age-specific patterns of slow and fast sleep spindles, slow oscillations, and their coupling in children and adolescents aged 5-6, 8-11, and 14-18 years, and an adult sample of 20- to 26-year-olds. Critically, based on this, we then investigated how spindle and slow oscillation maturity substantiate age-related differences in their precise orchestration. While the predominant type of fast spindles was development-specific in that it was still nested in a frequency range below the canonical fast spindle range for the majority of children, the well-known slow oscillation-spindle coupling pattern was evident for sleep spindles in the adult-like canonical fast spindle range in all four age groups-but notably less precise in children. To corroborate these findings, we linked personalized measures of fast spindle maturity, which indicate the similarity between the prevailing development-specific and adult-like canonical fast spindles, and slow oscillation maturity, which reflects the extent to which slow oscillations show frontal dominance, with individual slow oscillation-spindle coupling patterns. Importantly, we found that fast spindle maturity was uniquely associated with enhanced slow oscillation-spindle coupling strength and temporal precision across the four age groups. Taken together, our results suggest that the increasing ability to generate adult-like canonical fast sleep spindles actuates precise slow oscillation-spindle coupling patterns from childhood through adolescence and into young adulthood.

Cells in the brain are wired together like an electric circuit that can relay information from one area of the brain to the next. Even when sleeping, the human brain continues to send signals to process information it has encountered during the day. This results in two patterns of electrical activity that define the sleeping brain: slowly repeating waves (or slow oscillations) and rapid bursts of activity known as sleep spindles. Although slow oscillations and sleep spindles are generated in different regions of the brain, they often happen at the same time. This syncing of activity is thought to help different parts of the brain to communicate with each other. Such communication is essential for new memories to become stable and last a long time. In children, slow oscillations and sleep spindles appear together less frequently, suggesting that these co-occurring patterns of electrical activity develop as humans grow into adults. Here, Joechner et al. set out to understand what drives slow oscillations and sleep spindles to start happening at the same time. The team used a technique called electroencephalography (or EEG for short) to study the brain activity of children, teenagers and adults as they slept. This revealed that slow oscillations and sleep spindles occur together less often in children compared to teenagers and adults. Moreover, the slow oscillations and sleep spindles observed in the children had very different physical characteristics to those observed in adults. Further analyses showed that the more similar the children's sleep spindles were to adult spindles, the more consistently they appeared at the same time as the slow oscillations. The findings of Joechner et al. suggest that as children grow up, their sleep spindles become more adult-like, causing the spindles to happen at the same time as slow oscillations more consistently. This indicates that brain circuits that generate sleep spindles may play an essential role in developing successful communication networks in the human brain. In the future, this work may ultimately provide new insights into how age-related changes to the brain contribute to cognitive development, and suggests sleep as a potential intervention target for neurodevelopmental disorders.

Preliminary Results: The Impact of Smartphone Use and Short-Wavelength Light during the Evening on Circadian Rhythm, Sleep and Alertness.

Smartphone usage strongly increased in the last decade, especially before bedtime. There is growing evidence that short-wavelength light affects hormonal secretion, thermoregulation, sleep and alertness. Whether blue light filters can attenuate these negative effects is still not clear. Therefore, here, we present preliminary data of 14 male participants (21.93 ± 2.17 years), who spent three nights in the sleep laboratory, reading 90 min either on a smartphone (1) with or (2) without a blue light filter, or (3) on printed material before bedtime. Subjective sleepiness was decreased during reading on a smartphone, but no effects were present on evening objective alertness in a GO/NOGO task. Cortisol was elevated in the morning after reading on the smartphone without a filter, which resulted in a reduced cortisol awakening response. Evening melatonin and nightly vasodilation (i.e., distal-proximal skin temperature gradient) were increased after reading on printed material. Early slow wave sleep/activity and objective alertness in the morning were only reduced after reading without a filter. These results indicate that short-wavelength light affects not only circadian rhythm and evening sleepiness but causes further effects on sleep physiology and alertness in the morning. Using a blue light filter in the evening partially reduces these negative effects.

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.

Comparative placebo-controlled polysomnographic and psychometric studies on the acute effects of gabapentin versus ropinirole in restless legs syndrome.

The aim of the present placebo-controlled sleep laboratory study was to compare the acute effects of gabapentin (GBT) and ropinirole (ROP) in restless legs syndrome (RLS). In a parallel-group design, 40 RLS patients received 300 mg GBT and another 40 patients 0.5 mg ROP as compared with placebo. Polysomnographic and psychometric measures were obtained in three sleep laboratory nights (screening/placebo/drug). Statistics included a Wilcoxon test for differences between drug and placebo and a U test for inter-group differences. Sleep efficiency and latency were found significantly improved after GBT, while they remained unchanged after ROP, with significant inter-drug differences. Sleep architecture showed oppositional changes after the two drugs: While GBT decreased S1, increased slow-wave sleep and SREM and shortened REM latency, ROP increased S2, decreased slow-wave sleep and SREM and increased REM latency. Periodic leg movements (PLM) showed a significantly greater decrease after ROP (-73%) than after GBT (-35%). Subjective sleep quality improved significantly only after GBT; mental performance improved after both drugs with no inter-drug differences. In conclusion, the dopamine agonist ROP showed acute therapeutic efficacy with regard to PLM measures only, whereas GBT had a less pronounced effect on these measures, but improved objective and subjective sleep and awakening quality as compared with both placebo and ROP. Differential acute drug effects may serve as prognostic indicators of therapeutic response of individual patients.

Computer-assisted sleep classification according to the standard of the American Academy of Sleep Medicine: validation study of the AASM version of the Somnolyzer 24 × 7.

BACKGROUND: In 2007, the AASM Manual for the Scoring of Sleep and Associated Events was published by the American Academy of Sleep Medicine (AASM). Concerning the visual classification of sleep stages, these new rules are intended to replace the rules by Rechtschaffen and Kales (R&K). METHODS: We adapted the automatic R&K sleep scoring system Somnolyzer 24 × 7 to comply with the AASM rules and subsequently performed a validation study based on 72 polysomnographies from the Siesta database (56 healthy subjects, 16 patients, 38 females, 34 males, aged 21-86 years). Scorings according to the AASM rules were performed manually by experienced sleep scorers and semi-automatically by the AASM version of the Somnolyzer. Manual scorings and Somnolyzer reviews were performed independently by at least 2 out of 8 experts from 4 sleep centers. RESULTS: In the quality control process, sleep experts corrected 4.8 and 3.7% of the automatically assigned epochs, resulting in a reliability between 2 Somnolyzer-assisted scorings of 99% (Cohen's kappa: 0.99). In contrast, the reliability between the 2 manual scorings was 82% (kappa: 0.76). The agreement between the 2 Somnolyzer-assisted and the 2 visual scorings was between 81% (kappa: 0.75) and 82% (kappa: 0.76). CONCLUSION: The AASM version of the Somnolyzer revealed an agreement between semi-automated and human expert scoring comparable to that published for the R&K version with a validity comparable to that of human experts, but with a reliability close to 1, thereby reducing interrater variability as well as scoring time to a minimum.

Additional Value of 2-[18F]FDG PET/CT Comparing to MRI in Treatment Approach of Anal Cancer Patients.

Accurate staging and treatment planning are imperative for precise management in Anal Cancer (ACa) patients. We aimed to evaluate the additive and prognostic value of pre-treatment 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) in the staging and management of ACa compared to magnetic resonance imaging (MRI). This retrospective study was conducted on 54 patients. Pre-treatment 2-[18F]FDG PET/CT studies and MRI reports were compared considering the primary tumor, pelvic lymph nodes, and metastatic lesions. The impact of 2-[18F]FDG PET/CT in the management and its prognostic value, using maximum standardized uptake value (SUVmax), were assessed. Discordant findings were found in 46.3% of patients (5 in T; 1 in T and N; 18 in N; and 1 in M stage). 2-[18F]FDG PET/CT resulted in up-staging in 9.26% and down-staging in 3.7% of patients. Perirectal lymph nodes were metabolically inactive in 12.9% of patients. Moreover, 2-[18F]FDG PET/CT resulted in management change in 24.1% of patients. Finally, SUVmax provided no prognostic value. 2-[18F]FDG PET/CT altered staging and management in a sizable number of patients in this study, and supports a need for a change in guidelines for it to be used as a routine complementary test in the initial management of ACa.