Neurobiology of Sleep and Circadian Rhythms最新文献

The magnitude of the stimulus to the biological clock will depend upon the distribution of circadian phototransduction circuits across the retinae and the spatial distribution of luminous stimuli in the environment. The present study compared nocturnal melatonin suppression for light exposures to the superior, inferior, nasal, and temporal retina in one eye independent of shading from the brow and the nose. The stimulus was a 40° diameter luminous disc, half of which was blue light (LED, λ_peak = 470 nm) and the other amber light (LED, λ_peak = 590 nm). Experimentally, the orientation of the bipartite disc was rotated to each of the four cardinal points of the visual field. A full, 40° blue disc was also employed by replacing the amber half-disc with another blue half-disc. The blue full- and half-discs always produced 100 photopic lx at the cornea. As hypothesized, nocturnal melatonin suppression was statistically greatest when the blue half-disc was delivered to the nasal hemi-field (35%); the other three hemi-fields were equally affected by the blue half-disc (≈20%). Melatonin suppression for the full-disc was 24%, which was not statistically different than the average suppression for the four hemi-fields of 27%.

In this commentary, I play the Devil’s advocate and assume the title of High Contrarian. I intend to be provocative to challenge long-standing ideas about sleep. I blame all on Professor Craig Heller, who taught me to think this way as a graduate student in his laboratory. Scientists should fearlessly jump into the foaming edge of what we know, but also consider how safe are their intellectual harbors. There are many ideas we accept as ‘known’: that sleep is ubiquitous in the animal kingdom, that it serves vital functions, that it plays an essential role in brain plasticity. All of this could be wrong. As one example, I reexamine the idea that sleep is regulated by a mysterious ‘homeostat’ that determines sleep need based on prior wake time.

Background

Relatively few studies investigated the association between rest-activity circadian rhythm and cognitive impairment in population-based study, and the evidence from Asian populations is sparse. We aimed to examine the relationship of actigraphy measured rest-activity circadian rhythm with mild cognitive impairment (MCI) or cognitive impairment in Hong Kong healthy community-dwelling older adults.

Methods

We recruited 174 Hong Kong healthy adults aged ≥65 years (36 male vs. 138 female) during April–September 2018, and followed up them for 12 months. Participants were invited to wear wrist actigraphy for 7 days in both baseline and follow-up study. We used the actigraph data to calculate their midline statistic of rhythm (MESOR), amplitude, acrophase and percent rhythm. Montreal Cognitive Assessment (MoCA) was used to assess their cognitive scores at baseline and follow-up. Multivariate logistic regression model was performed to estimate the association of rest-activity circadian rhythm parameters with MCI; whilst multinomial logistic regression model was used to examine the association between rhythm parameters and changes of cognitive scores (i.e., worsen: <-1, stable: -1 to 1, better cognition: ≥2) after 12-months follow-up respectively.

Results

There was no association between rest-activity circadian rhythm parameters and MCI or cognitive impairment at baseline. Compared to those with an averaged value of acrophase (1:24pm-3:00pm), results of multinominal logistic regression showed that participants with a delayed acrophase (after 3:00pm) were less likely to have better cognition (adjusted odds ratio (AOR) = 0.32, 95% confidence interval (CI) = 0.11–0.88). Upon one year of follow-up, participants who delayed their acrophase for 24 min than their baseline measurements were also less likely to have better cognitive functions (AOR = 0.26, 95%CI = 0.08–0.79).

Conclusions

Results from both the baseline survey and follow-up study consistently confirmed that older adults, especially in light of the majority of participants being the females, with delayed acrophase were less likely to have better cognition in the Asian population.

Automatic sleep stage scoring based on deep neural networks has come into focus of sleep researchers and physicians, as a reliable method able to objectively classify sleep stages would save human resources and simplify clinical routines. Due to novel open-source software libraries for machine learning, in combination with enormous recent progress in hardware development, a paradigm shift in the field of sleep research towards automatic diagnostics might be imminent. We argue that modern machine learning techniques are not just a tool to perform automatic sleep stage classification, but are also a creative approach to find hidden properties of sleep physiology. We have already developed and established algorithms to visualize and cluster EEG data, facilitating first assessments on sleep health in terms of sleep-apnea and consequently reduced daytime vigilance. In the following study, we further analyze cortical activity during sleep by determining the probabilities of momentary sleep stages, represented as hypnodensity graphs and then computing vectorial cross-correlations of different EEG channels. We can show that this measure serves to estimate the period length of sleep cycles and thus can help to find disturbances due to pathological conditions.

The circadian clock, which generates the internal daily rhythm largely mediated through release of melatonin, can be disrupted in various ways. Multiple factors result in a disruption of the circadian cycle in the clinical context, of interest are anti-cancer drugs such as cisplatin. Cisplatin modulates the circadian clock through two mechanisms: 1) the circadian clock control of DNA excision repair and 2) the effect of circadian clock disruption on apoptosis. Cisplatin can stimulate multiple classified molecules, including DNA repair factors, DNA damage recognition factors and transcription factors in drug resistance and cisplatin-induced signal transduction. These factors interact with each other and can be transformed by DNA damage. Hence, these molecular interactions are intimately involved in cell proliferation and damage-induced apoptosis. Cisplatin has a dual-effect on circadian genes: upregulation of CLOCK expression causes an increase in proliferation but upregulation of BMAL1 expression causes an increase in apoptosis. Therefore, the interference of circadian genes by cisplatin can have multiple, opposing effects on apoptosis and cell proliferation, which may have unintended pro-cancer effects. Melatonin and intracellular Ca²⁺ also have a dual-effect on cell proliferation and apoptosis and can disrupt circadian rhythms.

Sleep deprivation (SD) and fatigue have detrimental effects on performance in operational settings. Few studies have investigated the cumulative effects of SD and fatigue on performance under heavy workload demands. Therefore, we investigated the efficacy of multiple repeated doses of caffeine as a countermeasure to SD and fatigue during 77 h total SD (TSD) during the early morning hours. Twenty-three males and females, 18 – 35 years of age, who identified as moderate caffeine consumers completed the Psychomotor Vigilance Task (PVT) 141 times during the experimental test period. Caffeine was administered in a multi-dose paradigm over three nights without sleep. Participants received either caffeine (200 mg) or placebo at the beginning of each 2-h test block from 0100 – 0900 (800 mg total per night). While PVT speed declined for both groups across all 3 nights, the caffeine group consistently out-performed the placebo group. Caffeine maintained attentiveness (1-5 s lapses) on night 1, but this advantage was lost on nights 2 and 3. Caffeine outperformed placebo for responsive lapses (5-9 s lapses) across all three nights, but caffeine performance was still notably worse than at baseline. Prolonged non-responsive lapses (beyond 10 s) were only reduced by caffeine on night 2. Caffeine was more effective than placebo across all nights at sustaining completion speed of a complex motor sequence task and a manual coordination task. Essentially, caffeine is an effective countermeasure for SD, as it mitigates declines in speed and failures to respond, and sustains motor planning and coordination. However, caffeine does not restore normal functioning during SD and cannot be considered as a replacement for sleep.

Recently, it has been suggested that sleep problems in autism spectrum disorder (ASD) not only are associated symptoms, but may be deeply related to ASD pathogenesis. Common clinical practice relating to developmental disorders, has shown that parents of children with ASD have often stated that it is more difficult to raise children in the neonatal period because these children exhibit sleep problems. This study investigated the possibility that abnormal neonatal sleep-wake rhythms are related to future ASD development.

We administered questionnaires to assess parent(s) of children with ASD and controls. A retrospective analysis was conducted among 121 children with ASD (94 male and 27 female children) recruited from the K-Development Support Center for Children (K-ASD), 56 children with ASD (40 male and 16 female children) recruited from the H-Children's Sleep and Development Medical Research Center (H-ASD) and 203 children (104 male and 99 female children) recruited from four nursery schools in T-city (control).

Irritable/over-reactive types of sleep-wake rhythms that cause difficulty in raising children, such as 1) frequently waking up, 2) difficulty falling asleep, 3) short sleep hours, and 4) continuous crying and grumpiness, were observed more often in ASD groups than in the control group. Additionally, the number of the mothers who went to bed after midnight during pregnancy was higher in the ASD groups than in the control group.

Sleep-wake rhythm abnormalities in neonates may be considerable precursors to future development of ASD. Formation of ultradian and postnatal circadian rhythms should be given more attention when considering ASD development. Although this is a retrospective study, the results suggest that a prospective study regarding this issue may be important in understanding and discovering intervention areas that may contribute to preventing and/or properly treating ASD.

Purpose

We reported one patient infected with acute respiratory syndrome coronavirus-2 (SARS-CoV-2) presented with sleep disorders; insomnia and restless leg syndrome.

Methods

Patient data were obtained from medical records from Al-Raghy Isolation Hospital in Assuit University.

Results

A 49-year-old female patient presented with insomnia and restless leg syndrome associated with anosmia, ageusia. Three days before, she had developed a cough, malaise and athenia, headache, arthralgia, myalgia affecting mainly upper limbs, diarrhea and a fever followed by tachypnea. The naso-oropharyngeal swab test for coronavirus disease 2019 (COVID-19) by qualitative real-time reverse-transcriptase–polymerase-chain-reaction assay was positive. The patient was treated with Oseltamivir 75mg and clarithromycin 500 mg (12 hourly for each respectively) for 10 days with paracetamol. Two weeks later, the patient made a complete neurological and respiratory recovery.

Conclusion

Our case highlighted the rare occurrence of restless leg syndrome and insomnia during the COVID-19 pandemic. The era of sleep disorders spectrum in patients with COVID-19 remains to be characterized suggesting a frightening scientific association between COVID-19 and neuropsychiatric illness.