Sleep Reduction Research Articles

Relationship between physical activity, objective sleep parameters, and circadian rhythm in patients with head and neck cancer receiving chemoradiotherapy: A longitudinal study.

ObjectivesThis study was developed to assess the relationship between physical activity, sleep and circadian rhythm using accelerometer and urine melatonin levels in patients with head and neck cancer (HNC). Also, this study evaluated the changes in physical activity, sleep, and circadian rhythm during the seven‐week course of chemoradiotherapy.MethodsThis longitudinal study recruited 27 participants diagnosed with HNC who were planning to undergo chemoradiotherapy. Accelerometers worn for 3 days during the 1st, 3rd, and 7th weeks of chemoradiotherapy were used to assess physical activity levels (step count and metabolic equivalents [METs]) and sleep quality (total sleep time [TST], sleep onset latency [SOL], and sleep efficiency [SE]). Urine melatonin analysis was conducted using the morning void urine sample on 1st, 3rd, and 7th weeks. The change in variables during the seven weeks and the correlation between them were analyzed.ResultsDuring the seven weeks, trends of reduction in variables of physical activity, sleep and circadian rhythm were observed with significant decrease in step count, TST and melatonin levels. SE was found to have strong negative correlation with physical activity. TST was found to have moderate correlation with SE and step count. The variables of physical activity also showed moderate correlation among them.ConclusionThis study concludes that higher physical activity is associated with poor SE due to increased night‐time activity. There was a significant reduction in physical activity and sleep observed during seven weeks with moderate association between them. The significant circadian rhythm deregulation however showed poor association with the other variables.Level of Evidence: 2b

COVID-19, Mental health and intervention-priorities among Northern Italian University students

During the first wave of COVID-19 pandemic, the most affected area in Italy was the southeast part of the Lombardy region. The University of Brescia is one of the largest in Northern Italy. The aim of this study is to investigate the psychological and somatic symptoms driven by lifestyle changes due to the lockdown among the students of the University of Brescia.15261 University students were enrolled through institutional email;14302 were Master's and Bachelor's Degreestudents,724 were Residents and 235 doctorates.3553 students (23.28% of total),aged on average 22 years, completed the survey. Physical health, dietary and sleep habits, physical activities, economic and social issues were investigated through an anonymous, online ad hoc form, available until July 2020 and approved by the local Ethic Committee. Five psychosomatic outcomes were assessed: digestive disorders, headache, panic-anxiety crises, depression-sadness, fear od COVID-19.Factor analysis was applied to reduce the number of variables while logistic and ordinal logistic regression models were used to test the association between the latent variables and each outcome. Female gender, medium-intensive use of telephone, worsening of sleep quality, mnemonic difficulties and performance reduction were associated with all the outcomes. Low physical activity, increased time spent watching television and the worsening of dietary habits represented a significant risk factor for at least three of the outcomes. Despite the relatively low compliance, the survey clearly identified few priorities of intervention to prevent psychological and somatic effects of pandemic in the next future: circadian rhythm, nutritional habits, physical activity, use of media, gender issues. The results of this study show the psychosomatic effects of social isolation and the pandemic on a population at risk of young adults and can promote interventions to minimize the occurrence of psychosomatic consequences on young adults.Key messages Analysis of the main risk and protection factors in a population of young adults in the development of psycho-physical symptoms during the period of isolation due to the covid-19 pandemic.Support the need to implement public health services also to reduce health costs with possible methods of intervention, in harmony with the findings.

Роль фізичної активності в повсякденному житті сучасних школярів, які навчаються за різними програмами

Умови сучасного життя дають нам змогу спостерігати зміни у якісному відпочинку школярів та порівнювати їх із таким у школярів двадцять років тому. І можна з упевненістю сказати, що сьогодні школярі мають значно нижчий рівень фізичної активності, ніж 20 років тому, у зв’язку з тим, що сьогодення пропонує дуже багато альтернатив фізичній активності, а саме: телевізор, комп’ютер, планшет, телефон та інші сучасні іграшки. Усі ці пасивні ігри дуже цікаві й тому забирають майже весь час сучасного школяра, навіть шкільні підручники пропонуються в електронному вигляді. Питання ж фізичної активності стає більш актуальним із кожним днем. Усе більше батьків замислюються над необхідністю фізичного розвитку дитини такого ж ступеня, як і розумового. Отже, дослідження ступеня фізичної активності, його впливу на рівень розумової працездатності сучасних школярів, що навчаються за різними програмами, стає все більш актуальним.

Spontaneous eye blink rate mediates the relationship between sleepiness and impulsivity to negative stimuli

Previous studies have demonstrated that sleep deprivation results in a negativity bias, especially in the context of impaired response inhibition. In the present study we investigated spontaneous eye blink rate (EBR), a correlate of dopamine function, as a mediator of the relationship between subjective sleepiness and impulsivity toward negative stimuli on a Go/NoGo task. Participants rated their sleepiness on a number of measures including the Epworth Sleepiness Scale (ESS), the Karolinska Sleepiness Scale (KSS) and subscales of the Chronic Sleep Reduction Questionnaire (CSRQ). The findings revealed that EBR mediated the relationship between sleepiness as measured by the Karolinska Sleepiness Scale (KSS) and commission errors on negatively valanced stimuli. These findings suggest that reduced inhibition in responding to negative stimuli can be found as a function of subjective sleepiness and that changes in dopamine function may be one contributing factor explaining this relationship.

Registration of Electrophysiological Source Imaging With the BigBrain Using HCP Compatible Pipelines

This study examined the impact of using two abbreviated signal montages on the accuracy, precision and inter-scorer reliability of polysomnography (PSG) sleep and arousal scoring, compared to a standard reference montage, in a cohort of patients investigated for obstructive sleep apnoea (OSA). One abbreviated montage incorporated two signals dedicated to sleep and arousal scoring, and the other incorporated a single signal.Four scorers from two laboratories each scored 15 PSGS four times in random order: once using each abbreviated montage and twice using the reference montage.Use of the two-signal montage resulted in small changes in the distribution of sleep stages, a reduction in the arousal index and resultant reductions in sleep and arousal scoring agreement. For the one-signal montage, although similar magnitude sleep stage distribution changes were observed, there were larger reductions in the arousal index, and sleep and arousal scoring accuracy. Additionally, using the one-signal montage, there were statistically significant reductions in the precision of summary statistics including total sleep time (TST) and the amount of rapid eye movement (REM) sleep scored, and reductions in the inter-scorer reliability of REM sleep and arousal scoring.These findings demonstrate that abbreviated signal montages may result in underestimation of the arousal index and, depending on the montage, poorer precision in TST and REM sleep scoring, with potential consequences for apnoea–hypopnoea index (AHI) measures and OSA diagnosis. The results highlight the importance of careful evaluation of PSG results when using portable devices that have restricted signals, and they offer guidance for future PSG and portable monitoring standards.

Genetic and functional analysis reveals TENM4 contributes to schizophrenia

SummaryTENM4, encoding a member of the teneurin protein family, is a risk gene shared by many types of mental diseases and is implicated in neuronal plasticity and signaling. However, the role and the mechanisms of TENM4 in schizophrenia (SCZ) remain unclear. We identified possible pathogenic mutations in the TENM4 gene through target sequencing of TENM4 in 68 SCZ families. We further demonstrated that aberrant expression of Ten-m leads to lower learning ability, sleep reduction, and increased aggressiveness in animal models. RNA sequencing showed that aberrant expression of Ten-m was related to stimulus perception and metabolic process, and Gene Ontology enrichment terms were neurogenesis and ATPase activity. This study provides strong evidence that TENM4 contributes to SCZ, and its functional mutations might be responsible for the impaired neural circuits and behaviors observed in SCZ.

Cancer patient perspective in the arena of COVID‐19 pandemic

ObjectiveThe coronavirus disease 2019 (COVID‐19) outbreak has been declared a global pandemic of unprecedented proportions. Italy is a country which has been heavily affected. Cancer patients are at a higher risk owing to their intrinsic fragility related to their underlying disease and oncologic treatment. Against this backdrop, we conducted a survey to investigate how patients perceived their condition, clinical management and availability of information during the pandemic.MethodsBetween 15 April and 1 May 2020 a survey was submitted to cancer patients at oncology departments in the Marche region. Questions regarding the perception of personal safety, continuity of cancer care, information quality and psychological distress.ResultsSeven hundred patients participated in the survey; 59% were female and 40% were aged between 46 and 65. The majority of the participants perceived compliance with appropriate safety standards by cancer care providers and 80% were reassured about their concerns during the medical interview. 40% were worried of being at a higher risk of infection and 71% felt they were at a greater risk because of chemotherapy. 55% felt that postponing cancer treatment could reduce its efficacy, however 76% declared they did not feel abandoned at the time of treatment postponement. Patients between 46 and 65 years declared a significant reduction in sleep (p < 0.01) and in concentration (p = 0.03).ConclusionsThe emergency care offered to cancer patients has been deemed satisfactory in terms of both safety standards and care management. However, the majority of participants perceived the mutual negative influence between their oncologic disease and the risk of infection highlighting the need for special measures to ensure safe continuity of care.

Effects of artificial light with different wavelengths and irradiances on the sleep behaviors of Chestnut buntings (Emberiza rutila)

ABSTRACT Artificial light owns a rapid-expanding pattern, which may disrupt the sleep behaviors of birds roosting in illuminated urban areas. Whether the birds’ sleep would variably be affected by light with different wavelengths or intensities has not been broadly explored, and the species in Eastern China have rarely been investigated. The study chose Chestnut buntings that are a common migratory species flying via Eastern China as the subjects and investigated their sleep in response to five light spectrums at three ecologically relevant intensities. It shows that artificial light mainly delayed sleep onset, reduced sleep duration and increased frequency of awakenings, which to the largest degrees resulted in a 3-h delay of sleep onset, 25% reduction of sleep and 0.31 times/h more nocturnal awakenings. Awakening time was delayed at higher light intensity while being advanced in dimmed light. The effect of light spectrums overall ranked from the most to the least as 510 nm green, 580 nm yellow or white, and 470 nm blue or 620 nm orange light; the sleep parameters were affected more with higher light intensities. The study highlights the potential of adjusting spectral compositions of light source to mitigate the disturbance of artificial light to avian sleep.

Peculiarities of neuroregulatory mechanisms of adaptation under alcohol dependence (experimental study)

Neurophysiological and biochemical markers of alcohol dependence were identified in a study conducted in laboratory rats at the systemic and molecular levels. It has been shown that long-term alcohol consumption is accompanied by an increase in dopamine levels in the ventral tegmental area and a decrease in GABA and BDNF levels in the hippocampus and serum and leads to attenuation of neocortex control of the limbic emotional-motivational system of the brain. Disturbance of the mechanisms of structural and functional organization of wake-sleep processes and regulation of emotional reactions, which is reflected in the suppression of slow-wave sleep, reduction of paradoxical sleep, inhibition of positive emotional centers, the development of anxiety and depression have been determined. Key words: alcohol dependence, sleep-wake, anxiety, depression, catecholamines, GABA, BDNF

Sleep disturbance: The overlooked side after open heart surgery in adults.

Sleep is essential for full mental and physical renewal. Cardiac surgery improves the life expectancy and quality. But unfortunately, some patients lacked that merit as they suffered sleep disturbance. We used validated questionnaire applied to 153 cardiac surgery patients to assess the sleep disturbances after surgery. About 70 (45.8%) had valve procedure, 55 (36%) had revascularization, 19 (12.4%) had both procedures and 9 (5.8%) had other procedures. The majority had no post-operative bleeding nor infection. About 78% had sleeping difficulty for one month. About 50% used different medications to fall asleep, mostly analgesics. About 76% slept after 2-6 h irrespective of sleep quality. Some patients had poor sleep quality in the form of nightmares and night terrors. Sleep quality was disturbed immediately following cardiac surgery. There was a reduction of night sleep compensated by increased daytime sleepiness. These changes almost reverted one month after surgery.

Negative social jetlag - Special consideration of leisure activities and evidence from birdwatchers.

Birdwatching (birding) is a nature-based recreational activity, often including arising early in the morning. In the present study, we tested the effect of a negative social jetlag (SJL) in birders. Negative SJL implies that people have an even earlier sleep-wake rhythm on free days or weekends. As birds' activities start before or shortly after sunrise, especially during spring and early summer, birdwatchers follow this diurnal pattern. Further, birders are not homogeneous and vary greatly in recreational specialisation. The study was based on an online survey with 2,404 birdwatchers (55% male) who responded to questions about their sleep-wake times and about their birding activities. Birders show the same differences between weekdays and weekends/free days sleep like most other people. However, birdwatching days started earlier than weekdays (14min) and lasted longer. Thus, birdwatching days are shifted towards an earlier sleep-wake rhythm in total. Birdwatchers experience a sleep curtailment during birding. Instead of sleeping ~30min longer on weekends, they arise ~15min earlier, summing up to a sleep reduction of about ~45min compared to a regular weekend. The more psychologically committed birders are, the less they sleep, the earlier they arise, and the earlier is their midpoint of sleep on birdwatching days; meaning that highly specialised birders shift their sleep-wake rhythm to an earlier time compared to their regular weekend, and even their weekday sleep. Thus, birders may suffer more from the short- and long-term consequences of negative SJL. The results might stand representatively for other nature-related leisure activities.

007 NLRP3 inflammasomes contribute to dysregulated sleep and electroencephalogram delta power after mild and moderate TBI in mice

Abstract Introduction Most traumatic brain injuries (TBI) are mild to moderate and can cause persistent dysregulated sleep, although the mechanisms are not well understood. Interleukin-1 beta (IL-1β) is a pro-inflammatory molecule that is activated in the cortex after waking activity and pathogenic challenge and alters non-rapid eye movement (NREM) sleep and electroencephalogram (EEG) delta power. Nucleotide-binding domain leucine rich family pyrin containing 3 (NLRP3) inflammasomes sense changes in their local environment to stimulate caspase-1 to activate IL-1β into its mature form. We previously found that NLRP3 inflammasomes are increased in the cortex after acute sleep loss and contribute to increased NREM sleep and EEG delta power after sleep loss and toxin challenge. We aimed to determine if NLRP3 inflammasomes contribute to the persistent dysregulated sleep caused by TBI. Methods Using 2-3-month-old mice lacking NLRP3 and C57BL/6J wild-type control mice, we assessed sleep states and sleep state episode durations and frequencies prior to TBI, and 24 h, 2-weeks, and 2 months after mild or moderate TBI using polysomnography. TBI occurred in the frontal cortex from a controlled cortical impact device. Additional mice received identical treatments serving as a TBI procedural control but received a craniectomy without the TBI. Results Similar sleep findings were observed between the craniectomy control group and baseline measures. However, when compared to baseline values, mice lacking NLRP3 had attenuations in the significant increased amounts of NREM sleep and EEG delta power occurring 24 h after TBI and the significant reductions in NREM sleep and EEG delta power seen 2 months after TBI that were observed in wild-type mice. These effects were similar in moderate and mild TBI groups. Mice lacking NLRP3 were not found to exhibit the fragmented sleep after mild or moderate TBI that was found to persist from 24 h to 2 months post-TBI in the wild-type mice. These effects were evident by significant increased frequencies of waking episodes induced by the TBIs. Conclusion Our findings suggest that NLRP3 inflammasomes contribute to dysregulated sleep occurring acutely or more persistently after TBI. Support (if any) Career Development Award IBX002823 (MZ) and Merit Review Award I01RX001144 (GK) from the United States Department of Veterans Affairs

029 Median preoptic dual control over sleep regulation

Abstract Introduction Previous studies suggest that the median preoptic nucleus (MnPO) plays an important role in regulating the wake-sleep cycle and in particular homeostatic sleep drive. However, the precise cellular phenotypes, targets and central mechanisms by which the MnPO neurons regulate the wake-sleep cycle remain unknown. Both glutamatergic (Vglut2+) and GABAergic (Vgat+) MnPO neurons innervate brain regions implicated in sleep promotion and maintenance, suggesting that both cell types may participate on sleep control. Methods In this study, we used two genetically-targeted approaches associated with electroencephalographic (EEG) and electromyographic (EMG) recordings in Vgat-IRES-cre and Vglut2-IRES-cre mice to investigate the role of the MnPOVgat and MnPOVglut2 neurons in modulating wake-sleep behavior. Results First, using a chemogenetic approach, we found that activation of MnPOVgat neurons reduced the latency for the first NREM sleep episode, produced an increase in NREM sleep and reduced wakefulness. Then, to test the role of MnPOVgat and MnPOVglut2 neurons in regulating sleep homeostasis, we recorded EEG and EMG responses in mice that had the Vgat+ or Vglut2+ neurons deleted from the MnPO. After deletion of MnPOVgat neurons, mice showed a reduction of NREM sleep and an increase in wakefulness during the light phase. Deletion of MnPOVgat neurons also reduced sleep recovery after 4 hours of sleep deprivation (SD). On the other hand, deletion of the MnPOVglut2 neurons did not change the wake-sleep cycle during the 24h baseline condition, but prevented the sleep recovery immediately after SD. To understand the underlying mechanism in preventing sleep recovery in both MnPOVglut2- and MnPOVgat-deleted mice groups, we exposed these animals to a psychological stress protocol. In response to a psychological stressor, mice with deletion of glutamatergic, but not GABAergic MnPO neurons, had an exacerbation of the stress-induced insomnia. Conclusion Our results suggest that both neuron populations differentially participate in wake-sleep control, with MnPOVgat neurons being critically involved in sleep homeostasis, and MnPOVglut2 neurons promoting sleep during allostatic (stressful) challenges. Support (if any) NIH Grants NS085477, NS072337, HL095491 and Sleep Research Society Foundation (Award 026-JP-20).

Effects of Non‐contingent and Self‐administered Oxycodone on Sleep Architecture in Rats

Opioid use disorder (OUD) is an ongoing global public health concern. Opioid analgesics such as oxycodone are major contributors to this epidemic because of their abuse potential. Thus, understanding acute and long-term effects of opioid exposure is critical. Sleep disturbances are commonly reported yet understudied symptoms of OUD commonly associated with relapse. Normalizing the sleep disturbances associated with OUD could be a novel therapeutic approach for relapse prevention. No study to date has assessed progressive changes in sleep/wake architecture following contingent or non-contingent oxycodone exposure in animals. In the present studies, effects of oxycodone on sleep/wake architecture and quantitative electroencephalography (EEG) were examined in freely moving, Sprague-Dawley rats implanted with EEG surface electrodes and wireless transmitters. 24 hr EEG home cage recordings were scored manually as wake, rapid eye movement (REM) and non-REM (NREM) sleep. In one cohort, effects of acute, noncontingent oxycodone (1-3 mg/kg; sc) were examined when administered 2 hr into the light cycle. Oxycodone dose-dependently increased time awake and reduced NREM and REM sleep duration. Spectral power analysis showed that oxycodone dose-dependently increased high frequency gamma power (50-100Hz). In a second cohort, rats were implanted with both EEG implants and intravenous jugular catheters to examine effects of oxycodone self-administration (SA) on sleep. Rats were trained to self-administer sucrose pellets on a fixed ratio 3 (FR3) schedule of reinforcement during the first 2 hours of the dark cycle. Next, rats were divided into two groups; half continued to self-administer sucrose pellets, while the other self-administered oxycodone (0.056 mg/kg/inf for 7 days; then 0.1 mg/kg/inf for 10 days). On average, rats self-administered 1.04 mg/kg oxycodone per 2-hr session. Rats then underwent response extinction for 5 days where the reinforcer and light cues were absent followed by a single light-cue elicited reinstatement session. EEG was recorded from the home cages for the remaining 22 hours per day. Preliminary data suggest that, compared to the last day of sucrose pellet SA, oxycodone SA increased time awake and decreased NREM and REM sleep. These changes were not seen in rats self-administering sucrose pellets. The increase in wake duration persisted throughout oxycodone SA sessions, but the reduction in REM sleep dissipated over time. Ongoing analyses are examining sleep during abstinence to determine whether abstinence-related changes in sleep occur in a similar manner to other illicit drug classes. The effects of noncontingent oxycodone are more prominent than self-administered despite similar total daily intake. Self-administration paradigms yielding higher daily intake may be necessary to engender greater sleep disturbances. Although preliminary, understanding the direct pharmacological effects of oxycodone self-administration on sleep will be beneficial to examine potential novel pharmacotherapies to normalize sleep disturbances associated with OUD.

Is COVID-19 Keeping us Up at Night? Stress, Anxiety, and Sleep Among Adult Twins.

In response to the COVID-19 pandemic, a variety of social distancing measures to mitigate the virus outbreak have been implemented. These measures may have unintended consequences on individuals’ well-being, such as increased stress, anxiety, and sleep disruptions. We investigated the extent to which individuals’ mental health status is associated with perceived changes in sleep amount and sleep quality among a sample of adult twin pairs (N = 909 pairs; 77% MZ, 23% DZ), less than a month after the outbreak was declared a pandemic by the World Health Organization. About half of participants reported no change in sleep amount (50.1%) or sleep quality (55.6%). Approximately one-third of the participants had increased amount of sleep (29.8%), and 32.9% reported a decrease in sleep quality. We found that stress and anxiety levels were associated with sleep reduction (ORs = 2.36 and 3.12 for stress and anxiety, respectively) and poorer sleep quality (ORs = 2.45 and 3.73 for stress and anxiety, respectively), even after taking into account between-family confounds. A much smaller association was observed between levels of stress and anxiety and increased sleep amount (ORs = 1.42 and 1.60 for stress and anxiety, respectively) and sleep quality (OR = 1.21 and 1.29 for stress and anxiety, respectively), which was no longer significant after controlling for between-family confounds. Our results demonstrate that stress and anxiety associated with the COVID-19 pandemic and social distancing measures may be linked to reduced sleep amount and quality.

MicroRNAs in Basolateral Amygdala Associated with Stress and Fear Memories Regulate Rapid Eye Movement Sleep in Rats.

Stress-related sleep disturbances are distressing clinical symptoms in posttraumatic stress disorder patients. Intensely stressful events and their memories change rapid eye movement (REM) sleep in animal models. REM sleep varies with individual differences of stress resilience or vulnerability. The basolateral amygdala (BLA) is a primary mediator of the effects of stress and fear memories on sleep. However, the molecular mechanisms in BLA regulating the effects of fear conditioning, shock training (ST) and context re-exposure (CTX) on REM sleep are not well known. MicroRNAs (miRNAs) are small, non-coding RNAs and posttranscriptional gene regulators of diverse biological processes. The aim of this study is to investigate ST- and CTX-altered miRNAs in the BLA of resilience and vulnerable animals and on REM sleep regulation. MiRNAs expression profiles in BLA were generated following ST and CTX using the Taqman Low Density rodent microRNA array. The altered BLA miRNAs expression and REM sleep reduction observed in ST and CTX vulnerable animals. AntagomiR-221 microinjection into BLA for one of the upregulated miRNAs, miR-221 in BLA, attenuated the REM sleep reduction. This study suggests that miRNAs in the BLA may play a significant role in mediating the effects of stress and fear memories on REM sleep.

NREM delta power and AD-relevant tauopathy are associated with shared cortical gene networks

Reduced NREM sleep in humans is associated with AD neuropathology. Recent work has demonstrated a reduction in NREM sleep in preclinical AD, pointing to its potential utility as an early marker of dementia. We test the hypothesis that reduced NREM delta power and increased tauopathy are associated with shared underlying cortical molecular networks in preclinical AD. We integrate multi-omics data from two extensive public resources, a human Alzheimer’s disease cohort from the Mount Sinai Brain Bank (N = 125) reflecting AD progression and a (C57BL/6J × 129S1/SvImJ) F2 mouse population in which NREM delta power was measured (N = 98). Two cortical gene networks, including a CLOCK-dependent circadian network, are associated with NREM delta power and AD tauopathy progression. These networks were validated in independent mouse and human cohorts. Identifying gene networks related to preclinical AD elucidate possible mechanisms associated with the early disease phase and potential targets to alter the disease course.

A subset of DN1p neurons integrates thermosensory inputs to promote wakefulness via CNMa signaling

Sleep is an essential and evolutionarily conserved behavior that is modulated by many environmental factors. Ambient temperature shifting usually occurs during climatic or seasonal change or travel from high-latitude area to low-latitude area that affects animal physiology. Increasing ambient temperature modulates sleep in both humans and Drosophila. Although several thermosensory molecules and neurons have been identified, the neural mechanisms that integrate temperature sensation into the sleep neural circuit remain poorly understood. Here, we reveal that prolonged increasing of ambient temperature induces a reversible sleep reduction and impaired sleep consolidation in Drosophila via activating the internal thermosensory anterior cells (ACs). ACs form synaptic contacts with a subset of posterior dorsal neuron 1 (DN1p) neurons and release acetylcholine to promote wakefulness. Furthermore, we identify that this subset of DN1ps promotes wakefulness by releasing CNMamide (CNMa) neuropeptides to inhibit the Dh44-positive pars intercerebralis (PI) neurons through CNMa receptors. Our study demonstrates that the AC-DN1p-PI neural circuit is responsible for integrating thermosensory inputs into the sleep neural circuit. Moreover, we identify the CNMa signaling pathway as a newly recognized wakefulness-promoting DN1 pathway.

A Pilot Study of the Government Pharmaceutical Organization (GPO) Cannabis Extract for Multiple Sclerosis (MS) Spasticity Treatment in Thailand

Background: The prevalence of spasticity in multiple sclerosis (MS) patients is nearly 90%. Most patients do not respond to current anti-spastic medications. Objective: To evaluate the efficacy and safety of Government Pharmaceutical Organization cannabis extract (GPOCE) in the treatment of spasticity in MS patients in Thailand. Materials and Methods: This prospective pilot study in patients diagnosed with MS whose spasticity was not relieved under current spasticity treatments, was performed between November 2019 and June 2020. The GPOCE formulation of THC:CBD 1:1 was administered to all patients. The treatment outcomes were determined at 12 weeks and compared with their baseline. Results: Seven patients participated in the present study. Among these, two patients withdrew after receiving only a small dose of GPOCE. Finally, five patients were included in the final analysis. The primary outcome was a reduction in the Modified Ashworth Score (MAS), which decreased among participants from a baseline of 15 (IQR 12 to 19) to 6 (IQR 1 to 12) (p=0.043). The key secondary outcome was a clinically relevant response (CRR), which was defined as a reduction of the spasticity Numeric Rating Scale (NRS) of more than thirty percent compared to baseline. Four patients (80%) achieved CRR. Moreover, the overall spasticity NRS decreased from a median of 6 (IQR5 to 7) to 2 (IQR2 to 3). A reduction of other NRS parameters, including fatigue, pain, tremor, sleep, spasm, anxiety, and depression, was also observed after treatment. Moreover, GPOCE was generally well tolerated. Conclusion: GPOCE is useful in treating spasticity in patients with MS. The safety profile is acceptable under the supervision of a health care provider. Keywords: Multiple sclerosis (MS), Cannabis extract, Spasticity

Splitting sleep between the night and a daytime nap reduces homeostatic sleep pressure and enhances long-term memory

Daytime naps have been linked with enhanced memory encoding and consolidation. It remains unclear how a daily napping schedule impacts learning throughout the day, and whether these effects are the same for well-rested and sleep restricted individuals. We compared memory in 112 adolescents who underwent two simulated school weeks containing 8 or 6.5 h sleep opportunities each day. Sleep episodes were nocturnal or split between nocturnal sleep and a 90-min afternoon nap, creating four experimental groups: 8 h-continuous, 8 h-split, 6.5 h-continuous and 6.5 h-split. Declarative memory was assessed with picture encoding and an educationally realistic factual knowledge task. Splitting sleep significantly enhanced afternoon picture encoding and factual knowledge under both 6.5 h and 8 h durations. Splitting sleep also significantly reduced slow-wave energy during nocturnal sleep, suggesting lower homeostatic sleep pressure during the day. There was no negative impact of the split sleep schedule on morning performance, despite a reduction in nocturnal sleep. These findings suggest that naps could be incorporated into a daily sleep schedule that provides sufficient sleep and benefits learning.