Mediation analysis of chronotype, sleep-related factors, and depressive symptoms among workers: a cross-sectional study.

Background: This study aimed to examine the impact of chronotype on depressive symptoms and explore the mediating effects of sleep quality, pre-sleep cognitive arousal, and social jetlag in a sample of wage earners. Methods: A total of 3,917 waged workers were surveyed online in July 2022. Logistic regression and mediation analysis were used to assess the relationship between chronotype (morningness, intermediate, and eveningness) and depressive symptoms (Patient Health Questionnaire ≥ 5), and the mediating effects of Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Pre-Sleep Arousal Scale (PSAS). All analyses were adjusted for age, education level, income level, marital status, coffee consumption, alcohol consumption, physical activity, occupation, employment status, and working hours to calculate odds ratios (ORs). Results: The chronotypes of all the participants were divided into morningness (4.7%), intermediate (93.5%), and eveningness (1.8%). Multiple logistic regression analysis showed an increased risk of depression in the eveningness chronotype (OR: 2.96; 95% confidence interval [CI]: 1.51, 5.86). Regarding the mediation analysis, ISI mediated 28.44% (95% CI: 16.39-40.5), PSQI for 31.25% (95% CI: 19.36, 43.15), and PSAS-Cognitive Score (PSAS-C) for 23.58% (95% CI: 10.66, 36.50) of the association between chronotype and depressive symptoms. However, social jetlag did not significantly mediate this relationship. (percentage mediated = 0.75%, 95% CI: -3.88, 5.39). Conclusions: Evening chronotypes exhibit an increased risk of depressive symptoms, which ISI, PSQI, and PSAS-C partially mediated. This suggests that interventions to improve sleep quality and maintain adequate sleep habits may effectively prevent and treat depression in employees with an eveningness chronotype.

Method for quantifying arousal and consciousness in healthy states and severe brain injury via EEG-based measures of corticothalamic physiology.

BACKGROUND: Characterization of normal arousal states has been achieved by fitting predictions of corticothalamic neural field theory (NFT) to electroencephalographic (EEG) spectra to yield relevant physiological parameters. NEW METHOD: A prior fitting method is extended to distinguish conscious and unconscious states in healthy and brain injured subjects by identifying additional parameters and clusters in parameter space. RESULTS: Fits of NFT predictions to EEG spectra are used to estimate neurophysiological parameters in healthy and brain injured subjects. Spectra are used from healthy subjects in wake and sleep and from patients with unresponsive wakefulness syndrome, in a minimally conscious state (MCS), and emerged from MCS. Subjects cluster into three groups in parameter space: conscious healthy (wake and REM), sleep, and brain injured. These are distinguished by the difference X-Y between corticocortical (X) and corticothalamic (Y) feedbacks, and by mean neural response rates α and ß to incoming spikes. X-Y tracks consciousness in healthy individuals, with smaller values in wake/REM than sleep, but cannot distinguish between brain injuries. Parameters α and ß differentiate deep sleep from wake/REM and brain injury. COMPARISON WITH EXISTING METHODS: Other methods typically rely on laborious clinical assessment, manual EEG scoring, or evaluation of measures like Φ from integrated information theory, for which no efficient method exists. In contrast, the present method can be automated on a personal computer. CONCLUSION: The method provides a means to quantify consciousness and arousal in healthy and brain injured subjects, but does not distinguish subtypes of brain injury.

Feel the beat: cape fur seal males encode their arousal state in their bark rate.

The cape fur seal is one of the most colonial mammal species in the world. Breeding colonies are composed of harems held by mature males (older than 10 years) with up to 30 females and their pups, while roaming subadult males (younger and socially immature) are kept away from bulls' territories. As in other pinnipeds, cape fur seals are highly vocal and use acoustic signals in all their social interactions. Males produce barks-short vocalizations always produced in sequences-for territorial defense, mating behaviors, and agonistic interactions. These calls convey information about the sex, age class, and individual identity. This study investigated whether motivational cues such as the arousal state can be encoded in territorial males' barks and whether these cues are decoded by listening sub-adult males. The rate (number of calls per unit of time) and fundamental frequency of barks were found to significantly increase during high arousal state interactions (i.e., male-male confrontation) compared to spontaneous barks. Playback experiments revealed that subadult males responded with a higher level of vigilance when territorial males' barks had a faster bark rate. This mechanism of decoding the bulls' arousal state from barks will likely constitute an advantage for both bulls and the subadult males, by avoiding or reducing physical conflicts, and thereby reducing energy expenditure and the risk of injury. This study is the first experimental evidence of cape fur seals' using vocal rhythmic patterns to modulate their social interactions.

Supplying the sleeping brain.

During sleep, the brain experiences large fluctuations in blood volume and altered coupling between neural and vascular signals.

Neurovascular coupling and bilateral connectivity during NREM and REM sleep.

To understand how arousal state impacts cerebral hemodynamics and neurovascular coupling, we monitored neural activity, behavior, and hemodynamic signals in un-anesthetized, head-fixed mice. Mice frequently fell asleep during imaging, and these sleep events were interspersed with periods of wake. During both NREM and REM sleep, mice showed large increases in cerebral blood volume ([HbT]) and arteriole diameter relative to the awake state, two to five times larger than those evoked by sensory stimulation. During NREM, the amplitude of bilateral low-frequency oscillations in [HbT] increased markedly, and coherency between neural activity and hemodynamic signals was higher than the awake resting and REM states. Bilateral correlations in neural activity and [HbT] were highest during NREM, and lowest in the awake state. Hemodynamic signals in the cortex are strongly modulated by arousal state, and changes during sleep are substantially larger than sensory-evoked responses.

Body temperature and sleep.

Sleep in mammals is accompanied by a decrease in core body temperature (CBT). The circadian clock in the hypothalamic suprachiasmatic nucleus regulates daily rhythms in both CBT and arousal states, and these rhythms are normally coupled. Reductions in metabolic heat production resulting from behavioral quiescence and reduced muscle tone along with changes in autonomic nervous system activity and thermoeffector activity contribute to the sleep-related fall in CBT. Reductions in sympathetic tone to the peripheral vasculature resulting in heat loss through the skin are reflected in a sleep-related increase in distal skin temperature that is a prominent feature of sleep onset in humans. Within a sleep episode, patterns of autonomic nervous system and thermoeffector activity and the ability to defend against heat and cold exposure differ during nonrapid eye movement (NREM) and rapid eye movement sleep. Anatomic and functional integration of the control of arousal states and thermoregulation occur in the preoptic/anterior hypothalamus. Subsets or warm-sensing neurons in the preoptic/anterior hypothalamus implicated in CBT regulation are spontaneously activated during sleep onset and NREM sleep compared to waking and may underlie sleep-related changes in autonomic nervous system and thermoeffector activity.

[Regulation action and nerve electrophysiology mechanism of acupuncture on arousal state in patients of primary insomnia].

OBJECTIVE: To compare the difference between acupuncture and estazolam on arousal state in patients of primary insomnia, and to explore its nerve electrophysiology mechanism. METHODS: Sixty-four patients of primary insomnia were randomized into an acupuncture group (32 cases) and a medication group (32 cases). After 3 patients were excluded, 31 cases in the acupuncture group and 30 cases in the medication group were included. Patients in the acupuncture group were treated with acupuncture at Sishencong (EX-HN 1), Anmian (Extra), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6), Shenmai (BL 62) as main acupoints, combined with supporting acupoints, once a day, five times per week, continuously for 4 weeks. Patients in the medication group were treated with oral administration of estazolam, once a day, continuously for 4 weeks. The Pittsburgh sleep quality index (PSQI) and mean sleep latency (MSL) of multiple sleep latency test (MSLT) were compared before and after treatment in the two groups; the polysomnography (PSG) was applied to monitor the indices regarding sleep structure. RESULTS: Compared before treatment, PSQI score was reduced after treatment in the two groups (both P<0.01), which was more significant in the acupuncture group (P<0.05). Compared before treatment, sleep onset latency (SOL), number of awakenings (NWAK) and wake after sleep onset (WASO) were reduced, while total sleep time (TST) and sleep efficiency (SE) were significantly increased in the two groups after treatment (all P<0.01). Compared before treatment, the percentage of non-rapid eye movement period 1/2/3 (N1, N2, N3) and the percentage of rapid eye movement period (REM) to TST were not significantly changed after treatment in the medication group (all P>0.05). Compared before treatment, the percentage of N1, N2 to TST was reduced, while the percentage of N3 and REM to TST was increased after treatment in the acupuncture group (P<0.01). The SOL, NWAK, WASO, TST, SE were not statistically changed after treatment in each group (all P>0.05). Compared with the medication group, the percentage of N1 and N2 was reduced while that of N3 and REM was increased after treatment in the acupuncture group (all P<0.01). After treatment, MSL of MSLT were obviously decreased in the two groups (both P<0.01), which were more significant in the acupuncture group (P<0.05). CONCLUSIONS: Acupuncture can more effectively improve sleep quality of primary insomnia than estazolam, and is more beneficial for regulation of hyperarousal state.

Relationship between the changes in M1 excitability after motor learning and arousal state as assessed by short-latency afferent inhibition.

To examine the factors that influence the inter-individual differences in the changes in primary motor cortex (M1) excitability seen after motor learning, we investigated the relationship between the amplitude of transcranial magnetic stimulation-induced motor evoked potentials (MEP) and short-latency afferent inhibition (SAI) after motor learning, based on the working hypothesis that SAI can be used to evaluate cortical acetylcholine (ACh) activity. To confirm this working hypothesis, we manipulated the arousal state of the subjects using a vigilance task, the outcomes of which might be correlated with cortical ACh activity, and investigated the effects of arousal state on SAI. As a result, we showed that SAI was significantly affected by arousal state. Consequently, we concluded that the subjects' arousal state during motor learning tasks is one of factors to influence on inter-individual differences in the changes in M1 excitability seen after motor learning tasks.

Regulation action and nerve electrophysiology mechanism of acupuncture on arousal state in patients of primary insomnia / 中国针灸

<p><b>OBJECTIVE</b>To compare the difference between acupuncture and estazolam on arousal state in patients of primary insomnia, and to explore its nerve electrophysiology mechanism.</p><p><b>METHODS</b>Sixty-four patients of primary insomnia were randomized into an acupuncture group (32 cases) and a medication group (32 cases). After 3 patients were excluded, 31 cases in the acupuncture group and 30 cases in the medication group were included. Patients in the acupuncture group were treated with acupuncture at Sishencong (EX-HN 1), Anmian (Extra), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6), Shenmai (BL 62) as main acupoints, combined with supporting acupoints, once a day, five times per week, continuously for 4 weeks. Patients in the medication group were treated with oral administration of estazolam, once a day, continuously for 4 weeks. The Pittsburgh sleep quality index (PSQI) and mean sleep latency (MSL) of multiple sleep latency test (MSLT) were compared before and after treatment in the two groups; the polysomnography (PSG) was applied to monitor the indices regarding sleep structure.</p><p><b>RESULTS</b>Compared before treatment, PSQI score was reduced after treatment in the two groups (both<0.01), which was more significant in the acupuncture group (<0.05). Compared before treatment, sleep onset latency (SOL), number of awakenings (NWAK) and wake after sleep onset (WASO) were reduced, while total sleep time (TST) and sleep efficiency (SE) were significantly increased in the two groups after treatment (all<0.01). Compared before treatment, the percentage of non-rapid eye movement period 1/2/3 (N1, N2, N3) and the percentage of rapid eye movement period (REM) to TST were not significantly changed after treatment in the medication group (all>0.05). Compared before treatment, the percentage of N1, N2 to TST was reduced, while the percentage of N3 and REM to TST was increased after treatment in the acupuncture group (<0.01). The SOL, NWAK, WASO, TST, SE were not statistically changed after treatment in each group (all>0.05). Compared with the medication group, the percentage of N1 and N2 was reduced while that of N3 and REM was increased after treatment in the acupuncture group (all<0.01). After treatment, MSL of MSLT were obviously decreased in the two groups (both<0.01), which were more significant in the acupuncture group (<0.05).</p><p><b>CONCLUSIONS</b>Acupuncture can more effectively improve sleep quality of primary insomnia than estazolam, and is more beneficial for regulation of hyperarousal state.</p>

Hypocretin/orexin antagonism enhances sleep-related adenosine and GABA neurotransmission in rat basal forebrain.

Hypocretin/orexin (HCRT) neurons provide excitatory input to wake-promoting brain regions including the basal forebrain (BF). The dual HCRT receptor antagonist almorexant (ALM) decreases waking and increases sleep. We hypothesized that HCRT antagonists induce sleep, in part, through disfacilitation of BF neurons; consequently, ALM should have reduced efficacy in BF-lesioned (BFx) animals. To test this hypothesis, rats were given bilateral IgG-192-saporin injections, which predominantly targets cholinergic BF neurons. BFx and intact rats were then given oral ALM, the benzodiazepine agonist zolpidem (ZOL) or vehicle (VEH) at lights-out. ALM was less effective than ZOL at inducing sleep in BFx rats compared to controls. BF adenosine (ADO), γ-amino-butyric acid (GABA), and glutamate levels were then determined via microdialysis from intact, freely behaving rats following oral ALM, ZOL or VEH. ALM increased BF ADO and GABA levels during waking and mixed vigilance states, and preserved sleep-associated increases in GABA under low and high sleep pressure conditions. ALM infusion into the BF also enhanced cortical ADO release, demonstrating that HCRT input is critical for ADO signaling in the BF. In contrast, oral ZOL and BF-infused ZOL had no effect on ADO levels in either BF or cortex. ALM increased BF ADO (an endogenous sleep-promoting substance) and GABA (which is increased during normal sleep), and required an intact BF for maximal efficacy, whereas ZOL blocked sleep-associated BF GABA release, and required no functional contribution from the BF to induce sleep. ALM thus induces sleep by facilitating the neural mechanisms underlying the normal transition to sleep.