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Abstract Improving our learning abilities is important for numerous aspects of our life. Several studies found beneficial effects of presenting cues (odor or sounds) during learning and during sleep for memory performance. A recent study applying a real-life paradigm indicated that additional odor cueing during a Final Test can further increase this cueing effect. The present online study builds on these findings with the following questions: (1) Can we replicate beneficial memory effects of additional odor cueing during tests? (2) How many odor cueing learning sessions and odor cueing nights of sleep maximize the learning success? (3) Can odor cueing also reduce the amount of forgetting over time? 160 Participants learned 40 German Japanese word pairs in four groups with separate experimental conditions over three days. Group N received no odor during the whole study. Group LS received odor cueing during learning and sleep, group LT during learning and testing and group LST during learning, sleep and testing. Participants performed intermediate tests after each learning session plus three final tests 1, 7 and 28 days after the last learning session. Results: (1) Group LST learned 8.5% more vocabulary words than the other groups overall. (2) This odor cueing effect increased across the three days of cued learning. (3) We found no clear evidence for effects of odor cueing on the forgetting dynamics. Our findings support the notion of a beneficial effect of odor cueing. They further suggest to use at least 3 days and nights of odor cueing. Overall, this study indicates that there is an easy, efficient and economical way to enhance memory performance in daily life.

The last ten years have seen the development and publication of numerous national and international guidelines devoted to the diagnosis and treatment of insomnia. These include guidelines by the American College of Physicians (ACP), the American Academy of Sleep Medicine (AASM), the British Sleep Society (BSS), the German Sleep Society (GSS), and the European Sleep Research Society (ESRS). Though coming from very diverse authors and backgrounds, these guidelines by and large agree concerning the therapeutic recommendations: cognitive behavioral treatment of insomnia (CBT-I), a multicomponent psychotherapeutic intervention, is unequivocally recommended as a first-line treatment. In this report, we will focus on the most recent guideline update from the ESRS, which was published in November 2023. After suggesting a careful diagnostic procedure, CBT-I, both applied face to face (F2F) or digitally (dCBT-I), is again recommended as a first-line treatment based on the available evidence. Hypnotic medications like benzodiazepines (BZ), benzodiazepine receptor agonists (BZRA), sedating antidepressants, and others are approved for short-term-treatment of up to four weeks. Orexin receptor antagonists (i.e., daridorexant) and prolonged release melatonin are considered as options for longer-term treatment when carefully considering the advantages and disadvantages. Both light therapy and exercise regimens were viewed as promising; however, they still lack convincing evidence for the time being. Given the fact that not every patient responds satisfactorily or even remits following CBT-I or other treatment options, the research agenda calls for the development and evaluation of new therapeutic avenues and combination therapies.

Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools for remote control of targeted cell populations using chemical actuators that bind to modified receptors. Despite the popularity of DREADDs in neuroscience and sleep research, potential effects of the DREADD actuator clozapine-N-oxide (CNO) on sleep have never been systematically tested. Here, we show that intraperitoneal injections of commonly used CNO doses (1, 5, and 10 mg/kg) alter sleep in wild-type male laboratory mice. Using electroencephalography (EEG) and electromyography (EMG) to analyse sleep, we found a dose-dependent suppression of rapid eye movement (REM) sleep, changes in EEG spectral power during non-REM (NREM) sleep, and altered sleep architecture in a pattern previously reported for clozapine. Effects of CNO on sleep could arise from back-metabolism to clozapine or binding to endogenous neurotransmitter receptors. Interestingly, we found that the novel DREADD actuator, compound 21 (C21, 3 mg/kg), similarly modulates sleep despite a lack of back-metabolism to clozapine. Our results demonstrate that both CNO and C21 can modulate sleep of mice not expressing DREADD receptors. This implies that back-metabolism to clozapine is not the sole mechanism underlying side effects of chemogenetic actuators. Therefore, any chemogenetic experiment should include a DREADD-free control group injected with the same CNO, C21, or newly developed actuator. We suggest that electrophysiological sleep assessment could serve as a sensitive tool to test the biological inertness of novel chemogenetic actuators.

The protein brain-derived neurotrophic factor (BDNF) promotes neural plasticity of the central nervous system and plays an important role for learning and memory. A single nucleotide polymorphism (rs6265) at position 66 in the pro-region of the human BDNF gene, resulting in a substitution of the amino acid valine (val) with methionine (met), leads to attenuated BDNF secretion and has been associated with reduced neurocognitive function. Inhomogeneous results have been found regarding the effect of the BDNF genotype on behavior. We determined the BDNF genotype and performance on the Compound Remote Associate (CRA) task as a common measure of creativity in 76 healthy university students. In our main analyses, we did not find significant differences between met-carriers (n = 30) and non-met carriers (n = 46). In a secondary analysis, we found that met-carriers had a slower solution time (medium effect size) for items of medium difficulty. Our results suggest that met-carriers and non-met-carriers do not generally differ regarding their creativity, but non-met-carriers may have a certain advantage when it comes to moderately difficult problems. The wider literature suggests that both genetic variants come with advantages and disadvantages. Future research needs to sharpen our understanding of the disadvantages and, potentially, advantages met allele carriers may have.

Chronic insomnia (insomnia disorder—ID) afflicts up to 10% of the adult population, increases with age and affects more women than men. ID is associated with significant daytime impairments and an increased risk for developing major somatic and mental disorders, especially depression and anxiety disorders. Almost all insomnia models assume persistent hyperarousal on cognitive, emotional, cortical and physiological levels as a central pathophysiological component. The marked discrepancy between only minor objective alterations in polysomnographic parameters of sleep continuity and the profound subjective impairment in patients with insomnia is still puzzling. We and others have proposed that alterations in the microstructure of sleep, especially in REM sleep (REM sleep instability), may explain this discrepancy and be at the core of the experience of fragmented and poor sleep in ID. The REM sleep instability concept is based on evidence showing REM time to be related to subjective wake time in insomnia as well as increased micro- and macro-arousals during REM sleep in insomnia patients compared to good-sleeper controls. Our own work showed that ID patients awoken from REM sleep more frequently reported the perception of having been awake than good sleepers as well as having had more negative ideations. The continuous measurement of event-related potentials throughout the whole night demonstrated reduced P2 amplitudes specifically during phasic REM sleep in insomnia, which points to a mismatch negativity in ID reflecting automatic change detection in the auditory system and a concomitant orienting response. REM sleep represents the most highly aroused brain state during sleep and thus might be particularly prone to fragmentation in individuals with persistent hyperarousal, resulting in a more conscious-like wake experience reflecting pre-sleep concerns of patients with ID, i.e., worries about poor sleep and its consequences, thus leading to the subjective over-estimation of nocturnal waking time and the experience of disrupted and non-restorative sleep. Chronic REM sleep instability might also lead to a dysfunction in a ventral emotional neural network, including limbic and paralimbic areas activated during REM sleep. Along with a postulated weakened functioning in a dorsal executive neural network, including frontal and prefrontal areas, this might contribute to emotional and cognitive alterations and an elevated risk of developing depression and anxiety.

Introduction It is unclear how internet-delivered cognitive-behavioural therapy for insomnia (CBT-I) can be integrated into healthcare systems, and little is known about the optimal level of therapist guidance. The aim of this study is to investigate three different versions of a stepped care model for insomnia (IG1, IG2, IG3) versus treatment as usual (TAU). IG1, IG2 and IG3 rely on treatment by general practitioners (GPs) in the entry level and differ in the amount of guidance by e-coaches in internet-delivered CBT-I.Methods and analysis In this randomised controlled trial, 4268 patients meeting International Classification of Diseases, Tenth Revision (ICD-10) criteria for insomnia will be recruited. The study will use cluster randomisation of GPs with an allocation ratio of 3:3:3:1 (IG1, IG2, IG3, TAU). In step 1 of the stepped care model, GPs will deliver psychoeducational treatment; in step 2, an internet-delivered CBT-I programme will be used; in step 3, GPs will refer patients to specialised treatment. Outcomes will be collected at baseline, and 4 weeks, 12 weeks and 6 months after baseline assessment. The primary outcome is insomnia severity at 6 months. An economic evaluation will be conducted and qualitative interviews will be used to explore barriers and facilitators of the stepped care model.Ethics and dissemination The study protocol was approved by the Ethics Committee of the Medical Centre—University of Freiburg. The results of the study will be published irrespective of the outcome.Trial registration number DRKS00021503.

Abstract Insomnia is defined as difficulties of initiating and maintaining sleep, early awakening and poor subjective sleep quality despite adequate opportunity and circumstances for sleep with impairment of daytime performance. These components of insomnia – namely persistent sleep difficulties despite of adequate sleep opportunity resulting in daytime dysfunction - appear secondary or co-morbid to neurological diseases. Comorbid insomnia originates from neurodegenerative, inflammatory, traumatic or ischemic changes in sleep regulating brainstem and hypothalamic nuclei with consecutive changes of neurotransmitters. Symptoms of neurological disorders (i.e motor deficits), co-morbidities (i.e. pain, depression, anxiety) and some disease-specific pharmaceuticals may cause insomnia and/or other sleep problems. This guideline focuses on insomnias in headaches, neurodegenerative movement disorders, multiple sclerosis, traumatic brain injury, epilepsies, stroke, neuromuscular disease and dementia. The most important new recommendations are: Cognitive behavioral therapy (CBTi) is recommended to treat acute and chronic insomnia in headache patients. Insomnia is one of the most frequent sleep complaints in neurodegenerative movement disorders. Patients may benefit from CBTi, antidepressants (trazodone, doxepin), melatonin and gaba-agonists. Insomnia is a frequent precursor of MS symptoms by up to 10 years. CBTi is recommended in patients with MS, traumatic brain injury and. Melatonin may improve insomnia symptoms in children with epilepsies. Patients with insomnia after stroke can be treated with benzodiazepine receptor agonists and sedating antidepressants. For patients with dementia suffering from insomnia trazodone, light therapy and physical exercise are recommended.

“Why treat insomnia?” This question grows out of the perspective that insomnia is a symptom that should only receive targeted treatment when temporary relief is needed or until more comprehensive gains may be achieved with therapy for the parent or precipitating medical or psychiatric disorders. This perspective, however, is untenable given recent data regarding the prevalence, course, consequences, and costs of insomnia. Further, the emerging data that the treatment of insomnia may promote better medical and mental health (alone or in combination with other therapies) strongly suggests that the question is no longer “why treat insomnia,” but rather “when isn’t insomnia treatment indicated?” This perspective was recently catalyzed with the American College of Physicians’ recommendation that chronic insomnia should be treated and that the first line treatment should be cognitive-behavioral therapy for insomnia (CBT-I).

Objectives: One of the largest clusters of Covid-19 infections was observed in Italy. The population was forced to home confinement, exposing individuals to increased risk for insomnia, which is, in turn, associated with depression and anxiety. Through a cross-sectional online survey targeting all Italian adult population (≥18 yrs), insomnia prevalence and its interactions with relevant factors were investigated.Methods: The survey was distributed from 1st April to 4th May 2020. We collected information on insomnia severity, depression, anxiety, sleep hygiene behaviors, dysfunctional beliefs about sleep, circadian preference, emotion regulation, cognitive flexibility, perceived stress, health habits, self-report of mental disorders, and variables related to individual difference in life changes due to the pandemic's outbreak.Results: The final sample comprised 1,989 persons (38.4 ± 12.8 yrs). Prevalence of clinical insomnia was 18.6%. Results from multivariable linear regression showed that insomnia severity was associated with poor sleep hygiene behaviors [β = 0.11, 95% CI (0.07–0.14)]; dysfunctional beliefs about sleep [β = 0.09, 95% CI (0.08–0.11)]; self-reported mental disorder [β = 2.51, 95% CI (1.8–3.1)]; anxiety [β = 0.33, 95% CI (0.25–0.42)]; and depression [β = 0.24, 95% CI (0.16–0.32)] symptoms.Conclusion: An alarming high prevalence of clinical insomnia was observed. Results suggest that clinical attention should be devoted to problems of insomnia in the Italian population with respect to both prevention and treatment.

BackgroundCoronavirus disease 2019 (COVID-19) seriously affected the whole of Italy. The extreme virulence and the speed of propagation resulted in restrictions and home confinement. This change was immediately perceived by people who found themselves exposed to feelings of uncertainty, fear, anger, stress, and a drastic change in the diurnal but above all nocturnal lifestyle. For these reasons, we aimed to study the quality of sleep and its connection to distress levels and to evaluate how lifestyle changed in the Italian population during the lockdown.MethodsBy means of an Internet survey we recruited 6,519 adults during the whole of the COVID-19 lockdown (from March 10–1st phase to May 4–2nd phase). We investigated the sociodemographic and COVID-19-related information and assessed sleep quality using the Medical Outcomes Study–sleep scale (MOS-SS) and mental health with the short form of Depression, Anxiety, and Stress Scales–21 Items (DASS-21). Multiple logistic regression model was used to evaluate the multivariate association between the dependent variable (good sleeper vs. poor sleeper) and all the variables that were significant in the univariate analysis.ResultsA total of 3,562 (55.32%) participants reported poor sleep quality according to the MOS-Sleep Index II score. The multiple binary logistic regression results of poor sleepers revealed several risk factors during the outbreak restrictions: female gender, living in Central Italy, having someone close who died because of COVID-19, markedly changed sleep–wake rhythms characterized by earlier or postponed habitual bedtime, earlier habitual awakening time and reduced number of afternoon naps, and extremely severe levels of stress, anxiety, and depression.ConclusionThis is the first study designed to understand sleep quality and sleep habits during the whole of the lockdown period in the Italian population that provides more than 6,000 participants in a survey developed specifically for the health emergency related to COVID-19. Our study found that more than half of the Italian population had impaired sleep quality and sleep habits due to elevated psychological distress during the COVID-19 lockdown containment measures. A multidisciplinary action should be undertaken in order to plan appropriate responses to the current crisis caused by the lockdown for the COVID-19 outbreak.

Introduction: Insomnia symptoms are very common in Bipolar Disorder. Our aim was to assess the potential association between insomnia, emotion dysregulation and suicidality in subjects with Bipolar Disorder. Methods: Seventy-seven subjects with Bipolar Disorder type II with a depressive episode with mixed features were recruited. Patients were assessed with SCID-DSM-5, the Insomnia Severity Index (ISI), the Difficulties in Emotion Regulation Scale (DERS), the Scale for Suicide Ideation (SSI) while evaluating manic and depressive symptoms. Results: Subjects with insomnia symptoms compared to those without showed higher scores in the DERS scale and subscales, including impulsivity, and in the SSI scale. Insomnia symptoms significantly predicted the severity of depressive symptoms, emotion dysregulation, and suicidality in subjects with bipolar disorder. In particular, insomnia was related to difficulties in some areas of emotion regulation including impulsivity. Emotion dysregulation significantly mediated the association between insomnia and depressive symptoms (Z = 2.9, p = 0.004). Furthermore, emotional impulsivity mediated the association between insomnia symptoms and suicidality (Z = 2.2, p = 0.03). Conclusion: In our study, subjects with bipolar disorder suffering from insomnia experienced a greater severity of depressive symptoms and suicidality compared to subjects without insomnia. Insomnia was associated with emotion dysregulation, impulsivity and suicidality. Further research is necessary to investigate if these latter features may benefit from early insomnia treatment in subjects with bipolar disorder.

Background Differentiating nonwear time from sleep and wake times is essential for the estimation of sleep duration based on actigraphy data. To efficiently analyze large-scale data sets, an automatic method of identifying these three different states is required. Therefore, we developed a classification algorithm to determine nonwear, sleep and wake periods from accelerometer data. Our work aimed to (I) develop a new pattern recognition algorithm for identifying nonwear periods from actigraphy data based on the influence of respiration rate on the power spectrum of the acceleration signal and implement it in an automatic classification algorithm for nonwear/sleep/wake states; (II) address motion artifacts that occur during nonwear periods and are known to cause misclassification of these periods; (III) adjust the algorithm depending on the sensor position (wrist, chest); and (IV) validate the algorithm on both healthy individuals and patients with sleep disorders. Methods The study involved 98 participants who wore wrist and chest acceleration sensors for one day of measurements. They spent one night in the sleep laboratory and continued to wear the sensors outside of the laboratory for the remainder of the day. The results of the classification algorithm were compared to those of the reference source: polysomnography for wake/sleep and manual annotations for nonwear/wear classification. Results The median kappa values for the two locations were 0.83 (wrist) and 0.84 (chest). The level of agreement did not vary significantly by sleep health (good sleepers vs. subjects with sleep disorders) (p = 0.348, p = 0.118) or by sex (p = 0.442, p = 0.456). The intraclass correlation coefficients of nonwear total time between the reference and the algorithm were 0.92 and 0.97 with the outliers and 0.95 and 0.98 after the outliers were removed for the wrist and chest, respectively. There was no evidence of an association between the mean difference (and 95% limits of agreement) and the mean of the two methods for either sensor position (wrist p = 0.110, chest p = 0.164), and the mean differences (algorithm minus reference) were 5.11 [95% LoA −15.4–25.7] and 1.32 [95% LoA −9.59–12.24] min/day, respectively, after the outliers were removed. Discussion We studied the influence of the respiration wave on the power spectrum of the acceleration signal for the differentiation of nonwear periods from sleep and wake periods. The algorithm combined both spectral analysis of the acceleration signal and rescoring. Based on the Bland-Altman analysis, the chest-worn accelerometer showed better results than the wrist-worn accelerometer.

Sleep deprivation is believed to lead to homeostatic increases in synaptic strength and reduced inducibility of associative LTP, based mainly on findings from animal studies. Here, Kuhn et al. demonstrate similar sleep-dependent synaptic plasticity changes in humans along with altered plasma BDNF levels.

Background: Childcare programs often include mandatory naptime during the day. Loss of daytime sleep could lead to a moderate-to-large decrease in self-regulation, emotion processing, and learning in early childhood. Nevertheless, daytime sleep has been less accurately studied than nighttime sleep. This study aims to explore the relationship between diurnal sleep habits in nursery settings, nocturnal sleep quality, and post-nap emotional intensity in infants and toddlers. Methods: Data of 92 children (52 girls, 40 boys) aged 6 to 36 months were obtained. Sleep habits as well as positive and negative emotions were monitored by educators during nursery times through a sleep and emotion diary for two weeks. Results: Explorative analyses showed that diurnal sleep hours decreased across age groups (except for females aged 25–36 months) and that all age groups had a lower amount of nocturnal sleep than is recommended by the National Sleep Foundation. Partial correlation analysis showed significant correlation between daytime sleep onset latency and positive emotions. Mediation analyses showed that daytime napping is relevant for emotional functioning independently of nocturnal sleep quality. Conclusions: Daytime sleep in early childhood seems to be linked to the management of positive and negative emotions and could play a role in healthy development of emotional processes.

(1) Background: An unresolved phenomenon of insomnia disorder is a discrepancy between objectively measured sleep and subjective complaints. It has been shown that rapid eye movement (REM) sleep might be especially vulnerable to an altered perception. The present work aimed to investigate the link between physiological REM parameters and mentation characteristics in REM sleep. (2) Methods: 22 patients with insomnia and 23 good sleepers indicating at least one REM mentation within an awakening study were included. Multivariate analyses of variance (MANOVAs) were calculated to examine group differences and effects of mentation characteristics on number of arousals, REM density, and spectral power prior to awakenings. (3) Results: Increased perceived wakefulness was related to lower delta, theta, and alpha power in the minute prior to the REM awakenings. Nevertheless, no group differences regarding spectral power were found. With respect to number of arousals and REM density, no significant effects of mentation characteristics and no group differences were found. (4) Conclusions: Our results suggest that spectral power in REM sleep is linked with altered sleep perception. Reduced delta, theta, and alpha power might be a signature of this modified REM sleep associated with a high level of perceived wakefulness. Future awakening studies are necessary to further explore the link between physiological REM parameters and sleep perception.

Objectives and Introduction: It is as yet unclear how polysomnographically determined sleep parameters determine emotional well-being both generally and particularly in patients with Insomnia Disorder (ID). ID is a frequent and disabling health condition associated with both day- and nighttime hyperarousal, linked to negative sleep-related ruminations as a cognitive component. Information on the immediate influence of objective sleep quality on emotional parameters is important for therapeutic approaches.Methods: The relationship between objective sleep parameters and two emotional questionnaire items obtained both for evening and morning, relaxation and emotional balance, was determined for both sleep lab nights in 161 ID patients and 161 age and gender matched good sleepers (retrospective sample from the Freiburg data base, 98 female, 63 male in each group, age ID: 42.16 ± 11.55, GSC: 41.91 ± 11.30 years). Multivariate mixed effects analysis, corrected for global influences of group, age and first/second night, was employed to determine between- and within-subject influences of sleep and emotional parameters.Results: Main effects: Within-subject, relaxation in the evening was strongly associated with sleep efficiency, REM latency and low arousal index in NREM sleep. No such influence was significant for emotional balance. Also between subjects, evening relaxation was related to increased sleep efficiency. Group interactions: Patients with larger relaxation values in the evening showed a larger reduction of the number of wake periods and the awakening index in NREM sleep than GSC subjects.Discussion: Unexpectedly, no general influence of emotional balance on sleep was found. The subjective feeling of relaxation, however, was associated with sleep efficiency, REM latency and low NREM sleep arousal index. While the first association may be obvious, a direct link to REM latency and NREM arousal index has not previously been shown. We could also directly observe that the number of wake periods in the PSG is more strongly influenced by evening relaxation in ID patients than in good sleepers, asserting the importance of sleep perception and attitude toward sleep in the therapeutic process.

To replicate the association between insomnia with objective short sleep duration and hypertension, type 2 diabetes and duration of insomnia.Retrospective case-control study.Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg.328 patients with primary insomnia classified according to DSM-IV criteria (125 males, 203 females, 44.3 ± 12.2 years).N/A.All participants were investigated using polysomnography, blood pressure measurements, and fasting routine laboratory.Insomnia patients with short sleep duration (< 6 hours) in the first night of laboratory sleep presented with a longer duration of insomnia compared to those with normal sleep duration (≥ 6 hours) in the first night of laboratory sleep. Insomnia patients who were categorised as short sleepers in either night were not more likely to suffer from hypertension (systolic blood pressure of ≥ 140 mm Hg, diastolic blood pressure of ≥ 90 mm Hg, or a previously established diagnosis). Data analysis showed that insomnia patients with objective short sleep duration were not more likely to suffer from type 2 diabetes (fasting plasma glucose level of ≥ 126 mg/dl, or a previously established diagnosis). However, the diabetes analysis was only based on a very small number of diabetes cases. As a new finding, insomnia patients who were categorised as short sleepers in either night presented with increases in liver enzyme levels.The finding on insomnia duration supports the concept of two distinct sub-groups of insomnia, namely insomnia with, and without, objectively determined short sleep duration. However, our data challenges previous findings that insomnia patients with short sleep duration are more likely to suffer from hypertension.