The preoptic area (POA) is necessary for sleep, but the fundamental POA circuits have remained elusive. Previous studies showed that galanin (GAL)- and GABA-producing neurons in the ventrolateral ...preoptic nucleus (VLPO) express cFos after periods of increased sleep and innervate key wake-promoting regions. Although lesions in this region can produce insomnia, high frequency photostimulation of the POA
neurons was shown to paradoxically cause waking, not sleep. Here we report that photostimulation of VLPO
neurons in mice promotes sleep with low frequency stimulation (1-4 Hz), but causes conduction block and waking at frequencies above 8 Hz. Further, optogenetic inhibition reduces sleep. Chemogenetic activation of VLPO
neurons confirms the increase in sleep, and also reduces body temperature. In addition, chemogenetic activation of VLPO
neurons induces short-latency sleep in an animal model of insomnia. Collectively, these findings establish a causal role of VLPO
neurons in both sleep induction and heat loss.
In children requiring electroencephalography (EEG), sleep recording can provide crucial information. As EEG recordings during spontaneous sleep are not always possible, pharmacological sleep-inducing ...agents are sometimes required. The aim of the study was to evaluate safety and efficacy of melatonin (Mel) and dexmedetomidine (Dex; intranasal and sublingual application) for sleep induction prior to EEG.
In this prospective randomized study, 156 consecutive patients aged 1-19 years were enrolled and randomized by draw into melatonin group (Mel;
= 54; dose: 0.1 mg/kg), dexmedetomidine (Dex) sublingual group (DexL;
= 51; dose: 3 mcg/kg) or dexmedetomidine intranasal group (DexN;
= 51; dose: 3 mcg/kg). We compared the groups in several parameters regarding efficacy and safety and also carried out a separate analysis for a subgroup of patients with complex behavioral problems.
Sleep was achieved in 93.6% of participants after the first application of the drug and in 99.4% after the application of another if needed. Mel was effective as the first drug in 83.3% and Dex in 99.0% (
< 0.001); in the subgroup of patients with complex developmental problems Mel was effective in 73.4% and Dex in 100% (
< 0.001). The patients fell asleep faster after intranasal application of Dex than after sublingual application (
= 0.006). None of the patients had respiratory depression, bradycardia, desaturation, or hypotension.
Mel and Dex are both safe for sleep induction prior to EEG recording in children. Dex is more effective compared to Mel in inducing sleep, also in the subgroup of children with complex behavioral problems.
Dexmedetomidine and Melatonin for Sleep Induction for EEG in Children, NCT04665453.
To compare Melatonin with Triclofos for efficacy (proportion of successful EEG, need of augmentation, sleep onset latency (SOL), yield of discharges, duration of sleep, presence and grade of ...artifacts) and tolerability (adverse effect profile).
A randomized trial was performed (block randomization). All children were advised regarding sleep deprivation, EEG technician administered the drug. EEG was labelled successful if at least 30 min of record could be obtained (sleep with or without awake state). Pediatric neurologist reported the EEG findings-sleep onset latency, epileptiform abnormalities and graded the artifacts (excess beta activity and movement artifacts if present). The parents were interviewed telephonically next day by a pediatric resident for any adverse effects. The parents, pediatric neurologist and pediatric resident were blinded for the drug given.
228 children were randomized (114 each received Melatonin and Triclofos). Both the groups were comparable at baseline for age group and demographic data. The proportion of successful EEG was 89.4% in Melatonin and 91.2% in Triclofos. First dose was effective in 64% in Melatonin and 63.15% in Triclofos group. Augmentation dose was needed in 25.4% in Melatonin and 28% in Triclofos group. Mean total sleep duration was 80 min after Melatonin and 82.39 after Triclofos administration. Adverse effects were observed in 6.14% of Melatonin and 8.65% of Triclofos group. None of the results were statistically significant.
There was no significant difference between efficacy and tolerability of Melatonin and Triclofos. Melatonin can be safely used to achieve sleep for EEG in children.
•First blinded randomized controlled trial of Melatonin with Triclofos to induce sleep for EEG.•No difference found in efficacy and tolerability of both the drugs when used for this indication.•Provides evidence to support the use of Melatonin as an alternative to Triclofos for short neuro physiological procedures.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The increased demand for well-being has fueled interest in sleep. Research in technology for monitoring sleep ranges from sleep efficiency and sleep stage analysis to sleep disorder detection, ...centering on wearable devices such as fitness bands, and some techniques have been commercialized and are available to consumers. Recently, as interest in digital therapeutics has increased, the field of sleep engineering demands a technology that helps people obtain quality sleep that goes beyond the level of monitoring. In particular, interest in sleep aids for people with or without insomnia but who cannot fall asleep easily at night is increasing. In this review, we discuss experiments that have tested the sleep-inducing effects of various auditory stimuli currently used for sleep-inducing purposes. The auditory stimulations were divided into (1) colored noises such as white noise and pink noise, (2) autonomous sensory meridian response sounds such as natural sounds such as rain and firewood burning, sounds of whispers, or rubbing various objects with a brush, and (3) classical music or a preferred type of music. For now, the current clinical method of receiving drugs or cognitive behavioral therapy to induce sleep is expected to dominate. However, it is anticipated that devices or applications with proven ability to induce sleep clinically will begin to appear outside the hospital environment in everyday life.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Rhynchophylline (RHY) is an alkaloid component of Uncaria, which are plants extensively used in traditional Asian medicines. Uncaria treatments increase sleep time and quality in humans, and RHY ...induces sleep in rats. However, like many traditional natural treatments, the mechanisms of action of RHY and Uncaria remain evasive. Moreover, it is unknown whether RHY modifies key brain oscillations during sleep. We thus aimed at defining the effects of RHY on sleep architecture and oscillations throughout a 24-h cycle, as well as identifying the underlying molecular mechanisms. Mice received systemic RHY injections at two times of the day (beginning and end of the light period), and vigilance states were studied by electrocorticographic recordings.
RHY enhanced slow wave sleep (SWS) after both injections, suppressed paradoxical sleep (PS) in the light but enhanced PS in the dark period. Furthermore, RHY modified brain oscillations during both wakefulness and SWS (including delta activity dynamics) in a time-dependent manner. Interestingly, most effects were larger in females. A brain spatial transcriptomic analysis showed that RHY modifies the expression of genes linked to cell movement, apoptosis/necrosis, and transcription/translation in a brain region-independent manner, and changes those linked to sleep regulation (e.g., Hcrt, Pmch) in a brain region-specific manner (e.g., in the hypothalamus).
The findings provide support to the sleep-inducing effect of RHY, expose the relevance to shape wake/sleep oscillations, and highlight its effects on the transcriptome with a high spatial resolution. The exposed molecular mechanisms underlying the effect of a natural compound should benefit sleep- and brain-related medicine.
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Sleep deficiency is linked to chronic health problems, such as heart disease, kidney disease, high blood pressure, diabetes, stroke, obesity, and depression. Healthcare practitioners are increasingly ...paying close attention to sleep and its impact on health and wellness as a measure of critical vitality. Sleep's impact on neurologic function, and cognitive endurance affect capacity throughout the lifespan. This article will address recent findings related to the potential of music to induce sleep in illness and wellness. Music therapy research findings and its efficacy as a potent cost-effective intervention will be highlighted.
The critical closing pressure (Pcrit) is the airway pressure at which the airway collapses and reflects the anatomical contribution to the genesis of obstructive sleep apnea. Pcrit is usually ...determined during non-rapid eye movement sleep at night, but has been determined under midazolam sedation during the day in the absence of sleep stage monitoring. Indeed, little is known about the effects of midazolam on sleep architecture. Moreover, deeper sedation with midazolam can decrease upper airway muscle activity and increase collapsibility compared with natural sleep. Pcrit under sedation has not been systematically compared with the usual method performed during natural sleep. Therefore, this study aimed to test the hypothesis that Pcrit following low doses of midazolam during the day would be comparable to Pcrit measured during natural sleep in the same patient. Fifteen men (age 54 ± 10 yr, body mass index 30 ± 4 kg/m(2)) with obstructive sleep apnea underwent a baseline standard overnight polysomnogram (apnea-hypopnea index 38 ± 22 events/h, range: 8-66 events/h), and Pcrit was determined during natural sleep and following midazolam. Sleep induction was obtained with low doses of midazolam (2.4 mg, range 2.0-4.4 mg), and sleep architecture was comparable to natural sleep. Natural sleep and induced sleep Pcrit were similar (-0.82 ± -3.44 and -0.97 ± 3.21 cmH(2)O, P = 0.663) and closely associated (intraclass correlation coefficient = 0.92; 95% confidence interval, 0.78-0.97, P < 0.001). Natural and midazolam-induced Pcrit correlated with obstructive sleep apnea severity, indicating that both Pcrit measures provided meaningful physiological information. Pcrit determined during the day with sleep induction is similar to natural overnight sleep and is a valid alternative approach in which to determine Pcrit.
Previous studies have shown that tryptophan and vitamin B6 used in conjunction with melatonin induce sleep more effectively than melatonin alone. This study aims at evaluating the efficacy of ...different dosages and timings of administration of a solution containing melatonin, tryptophan, and vitamin B6 for inducing sleep in children undergoing ABR testing.
294 children scheduled for Auditory Brain Response (ABR) evaluation were administered a solution containing melatonin, tryptophan, and vitamin B6 to induce sleep before the exam. Two different administration timings (pre-treatment and single shot treatment) and three dosages (0.5 ml in pre-treatment, 1.5 ml in pre-treatment, and 3 ml in single shot) were tested. The following parameters were evaluated: time needed for the subject to fall asleep before ABR testing, subject sl'eep features during ABR testing (quality, stability, duration), recorded ABR quality (including presence of abnormalities in amplitude and latency), subject waking up modality, and time needed for the subject to wake up at the end of the ABR exam.
Quality of ABR signals was similar across treatments, and subjects responded in a similar manner in terms of time needed to wake-up and wake-up modality. However, pretreatment with the 1.5 ml dose induced sleep faster than the two other dosages, and the length of the induced sleep was longer than that induced by pre-treatment with 0.5 ml. In general, the pre-treatment with 1.5 ml led to a shorter ABR exam, because reduces the time for inducing sleep, allows a long sleeping phase with a good quality, without variation in the wakening up times.
Melamil Tripto® is an alternative to sedative drugs for inducing sleep in pediatric subjects undergoing ABR testing. A pre-medication with 1.5 ml of MT 1 week before ABR testing further improves the strength of the solution.
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Summary This article reviews circadian thermoregulation in relation to sleep induction and phase of entrainment in the light of the comprehensive thermophysiological and chronobiological concepts of ...Jürgen Aschoff. The idea that temperature and sleep are interrelated is based on evolutionary history. Mammalian sleep developed in association with endothermy, and all species, independent of temporal niche, usually sleep during the circadian trough of their core body temperature (CBT) rhythm. The circadian pattern of CBT results from the balance between heat production and heat loss, the latter being relevant for sleep induction. Sleep under entrained conditions is typically initiated on the declining portion of the CBT curve when its rate of change and body heat loss is maximal. Body heat loss before lights off, via selective vasodilatation of distal skin regions, promotes sleepiness and the rapid onset of sleep. This thermophysiological effect represents the cement between the circadian clock and the sleep–wake cycle, and in turn determines phase of entrainment ( Ψ ) and sleep onset latency (SOL). These interrelationships have been recently studied in a particular subset of the general population, mainly women, who suffer from cold hands and feet (the so-called vasospastic syndrome, VS). Women with VS exhibit not only a lower capacity to lose heat during the daytime but also a prolonged SOL, a disturbed Ψ of the circadian clock with respect to the sleep–wake cycle and psychologically, a disposition to turn experienced anger inwards. This naturalistic model leads us to a more general conclusion that regulation of distal skin blood flow may have clinical relevance for insomnia, in particular sleep onset insomnia.
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In this paper, we present our study on investigating the effect of music for sleep induction and wake-up. Unlike existing studies that mostly focused on understanding how specific types of music ...affect sleep for insomnia patients or older people in laboratory conditions, we aim to study the effect of pop music with respect to the musical features on both sleep and wake-up of young adults without serious sleep disorder in the real-world environment. We conduct two extensive experiments, for which we carefully design a system consisting of hardware and software components for reliable data collection. Our analysis focuses on what types of musical features are effective for fast sleep induction and wake-up. Furthermore, we present two application scenarios of sleep music recommendation based on our findings.
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