Circadian rhythm mechanism in the suprachiasmatic nucleus and its relation to the olfactory system.

Animals need sleep, and the suprachiasmatic nucleus, the center of the circadian rhythm, plays an important role in determining the timing of sleep. The main input to the suprachiasmatic nucleus is the retinohypothalamic tract, with additional inputs from the intergeniculate leaflet pathway, the serotonergic afferent from the raphe, and other hypothalamic regions. Within the suprachiasmatic nucleus, two of the major subtypes are vasoactive intestinal polypeptide (VIP)-positive neurons and arginine-vasopressin (AVP)-positive neurons. VIP neurons are important for light entrainment and synchronization of suprachiasmatic nucleus neurons, whereas AVP neurons are important for circadian period determination. Output targets of the suprachiasmatic nucleus include the hypothalamus (subparaventricular zone, paraventricular hypothalamic nucleus, preoptic area, and medial hypothalamus), the thalamus (paraventricular thalamic nuclei), and lateral septum. The suprachiasmatic nucleus also sends information through several brain regions to the pineal gland. The olfactory bulb is thought to be able to generate a circadian rhythm without the suprachiasmatic nucleus. Some reports indicate that circadian rhythms of the olfactory bulb and olfactory cortex exist in the absence of the suprachiasmatic nucleus, but another report claims the influence of the suprachiasmatic nucleus. The regulation of circadian rhythms by sensory inputs other than light stimuli, including olfaction, has not been well studied and further progress is expected.

Circadian Rhythms of Body Temperature and Locomotor Activity in Spontaneously Hypertensive Rats under Frequent Changes in Light Conditions.

Changes in lighting accompany modern urbanization trends and can lead to various pathologies based on circadian disturbances. In this study, we assessed the changes in the circadian rhythm of core body temperature (Tcore) and locomotor activity of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) following exposure to different lighting conditions: extended light phase of the day (16 h-8 h, 20 h-4 h, 24 h-0 h), light pollution, monochromatic light, and bright light therapy. The telemetry data was collected after experimental lighting conditions during periods with standard lighting (12 h of light and 12 h of darkness) and was processed using linear and cosinor analysis. The daily rhythms of rats' parameters persisted in accordance with the standard lighting regime. Tcore changes were observed in both groups compared to the initial period: in WKY, a decrease in Tcore during the darkness and an increase during the light; in SHR, the opposite trend, with Tcore increased during the darkness and decreased during the light phase of the day. A relationship between Tcore and activity was observed with weak correlation. WKY exhibited more pronounced signs of adaptive variation and desynchronization compared to SHR, which could be associated with a wider range of functional capabilities of the organism without cardiovascular pathology.

Stroke in the Time of Circadian Medicine.

Time-of-day significantly influences the severity and incidence of stroke. Evidence has emerged not only for circadian governance over stroke risk factors, but also for important determinants of clinical outcome. In this review, we provide a comprehensive overview of the interplay between chronobiology and cerebrovascular disease. We discuss circadian regulation of pathophysiological mechanisms underlying stroke onset or tolerance as well as in vascular dementia. This includes cell death mechanisms, metabolism, mitochondrial function, and inflammation/immunity. Furthermore, we present clinical evidence supporting the link between disrupted circadian rhythms and increased susceptibility to stroke and dementia. We propose that circadian regulation of biochemical and physiological pathways in the brain increase susceptibility to damage after stroke in sleep and attenuate treatment effectiveness during the active phase. This review underscores the importance of considering circadian biology for understanding the pathology and treatment choice for stroke and vascular dementia and speculates that considering a patient's chronotype may be an important factor in developing precision treatment following stroke.

Long-term effects of environmental dynamic lighting on sleep-wake rhythm, mood and behaviour in older adults with intellectual disabilities.

BACKGROUND: Sleep-wake problems and depressive symptoms are common in people with intellectual disabilities (IDs) and are thought to be related to the unstable sleep-wake rhythm in this population. Previously, we showed that after increasing environmental light exposure, mid-sleep and sleep onset advanced, and mood improved over a period of 14 weeks after installing environmental dynamic light installations in the living room of people with IDs. We invited participants of that short-term study to take part in the current study on sleep-wake rhythm, mood and behaviour in older adults with IDs 1 year after installing environmental dynamic light installations in the common living rooms of six group homes. METHODS: A pre-post study was performed from October 2017 to February 2019. We included 45 participants (63.5 ± 8.5 years, 67% female) from six group home facilities who provided data at baseline (9, 4 and 1 weeks prior to installing light installations), short term (3, 7 and 14 weeks after installing light installations) and 1 year (54 weeks after installing light installations). Wrist activity was measured with actigraphy (GENEActiv) to derive the primary outcome of interdaily stability of sleep-wake rhythms as well as sleep estimates. Mood was measured with the Anxiety, Depression and Mood Scale. Behaviour was measured with the Aberrant Behaviour Checklist. RESULTS: One year after installing dynamic lighting, we did not find a change in interdaily stability. Total sleep time decreased (ß = -25.40 min; confidence interval: -10.99, -39.82), and sleep onset time was delayed (ß = 25.63 min; confidence interval: 11.18, 40.08). No effect on mood or behaviour was found. CONCLUSIONS: We did not find a change in sleep-wake rhythm, mood or behaviour in older persons with IDs living in care facilities 1 year after installing the light. We did find evidence for a long-term effect on sleep duration and sleep timing. The results have to be interpreted with care as the current study had a limited number of participants. The need for more research on the long-term effects of enhancing environmental light in ID settings is evident.

Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery.

The blood-brain barrier (BBB) is a critical interface separating the central nervous system from the peripheral circulation, ensuring brain homeostasis and function. Recent research has unveiled a profound connection between the BBB and circadian rhythms, the endogenous oscillations synchronizing biological processes with the 24-hour light-dark cycle. This review explores the significance of circadian rhythms in the context of BBB functions, with an emphasis on substrate passage through the BBB. Our discussion includes efflux transporters and the molecular timing mechanisms that regulate their activities. A significant focus of this review is the potential implications of chronotherapy, leveraging our knowledge of circadian rhythms for improving drug delivery to the brain. Understanding the temporal changes in BBB can lead to optimized timing of drug administration, to enhance therapeutic efficacy for neurological disorders while reducing side effects. By elucidating the interplay between circadian rhythms and drug transport across the BBB, this review offers insights into innovative therapeutic interventions.

Chrononutrition in traditional European medicine-Ideal meal timing for cardiometabolic health promotion.

Meal timing plays a crucial role for cardiometabolic health, given the circadian regulation of cardiometabolic function. However, to the best of our knowledge, no concept of meal timing exists in traditional European medicine (TEM). Therefore, in this narrative review, we aim to define the optimal time slot for energy intake and optimal energy distribution throughout the day in a context of TEM and explore further implications. By reviewing literature published between 2002 and 2022, we found that optimal timing for energy intake may be between 06:00 and 09:00, 12:00 and 14:00, and between 15:00 and 18:00, with high energy breakfast, medium energy lunch and low energy dinner and possibly further adjustments according to one's chronotype and genetics. Also, timing and distribution of energy intake may serve as a novel therapeutic strategy to optimize coction, a concept describing digestion and metabolism in TEM. Please cite this article as: Eberli NS, Colas L, Gimalac A. Chrononutrition in traditional European medicine-Ideal meal timing for cardiometabolic health promotion. J Integr Med. 2024; 22(2);115-125.

Circadian rhythm of intraocular pressure.

Intraocular pressure (IOP) plays a crucial role in glaucoma development, involving the dynamics of aqueous humor (AH). AH flows in from the ciliary body and exits through the trabecular meshwork (TM). IOP follows a circadian rhythm synchronized with the suprachiasmatic nucleus (SCN), the circadian pacemaker. The SCN resets peripheral clocks through sympathetic nerves or adrenal glucocorticoids (GCs). IOP's circadian rhythm is governed by circadian time signals, sympathetic noradrenaline (NE), and GCs, rather than the local clock. The activity of Na+/K+-ATPase in non-pigmented epithelial cells in the ciliary body can influence the nocturnal increase in IOP by enhancing AH inflow. Conversely, NE, not GCs, can regulate the IOP rhythm by suppressing TM macrophage phagocytosis and AH outflow. The activation of the ß1-adrenergic receptor (AR)-mediated EPAC-SHIP1 signal through the ablation of phosphatidylinositol triphosphate may govern phagocytic cup formation. These findings could offer insights for better glaucoma management, such as chronotherapy.

EEG rhythm separation and time-frequency analysis of fast multivariate empirical mode decomposition for motor imagery BCI.

Motor imagery electroencephalogram (EEG) is widely employed in brain-computer interface (BCI) systems. As a time-frequency analysis method for nonlinear and non-stationary signals, multivariate empirical mode decomposition (MEMD) and its noise-assisted version (NA-MEMD) has been widely used in the preprocessing step of BCI systems for separating EEG rhythms corresponding to specific brain activities. However, when applied to multichannel EEG signals, MEMD or NA-MEMD often demonstrate low robustness to noise and high computational complexity. To address these issues, we have explored the advantages of our recently proposed fast multivariate empirical mode decomposition (FMEMD) and its noise-assisted version (NA-FMEMD) for analyzing motor imagery data. We emphasize that FMEMD enables a more accurate estimation of EEG frequency information and exhibits a more noise-robust decomposition performance with improved computational efficiency. Comparative analysis with MEMD on simulation data and real-world EEG validates the above assertions. The joint average frequency measure is employed to automatically select intrinsic mode functions that correspond to specific frequency bands. Thus, FMEMD-based classification architecture is proposed. Using FMEMD as a preprocessing algorithm instead of MEMD can improve the classification accuracy by 2.3% on the BCI Competition IV dataset. On the Physiobank Motor/Mental Imagery dataset and BCI Competition IV Dataset 2a, FMEMD-based architecture also attained a comparable performance to complex algorithms. The results indicate that FMEMD proficiently extracts feature information from small benchmark datasets while mitigating dimensionality constraints resulting from computational complexity. Hence, FMEMD or NA-FMEMD can be a powerful time-frequency preprocessing method for BCI.

Effect of exercise based interventions on sleep and circadian rhythm in cancer survivors-a systematic review and meta-analysis.

Background: Disrupted circadian rhythm commonly reported in cancer survivors is closely associated with cancer related fatigue, sleep disturbances and compromised quality of life. As more cancer survivors request non-pharmacological treatment strategies for the management of their chronic sleep-related symptoms, there is a need for meta-analyses of various interventions such as exercise on sleep and circadian rhythm disturbances. Methods: A search for RCT's was conducted in April 2020 and updated in July 2023 using relevant keywords for cancer, sleep, circadian rhythm and exercise interventions on PubMed, Scopus, Web of Science, PEDro and CINAHL. Results: Thirty-six studies were included for qualitative analysis and 26, for meta-analysis. Thirty-five studies analyzed sleep outcomes, while five analyzed circadian rhythm. RCT's studying the effect of aerobic exercise, resistance exercise, combined aerobic and resistance exercise, physical activity, yoga, or tai chi were included. Meta-analysis results showed significant exercise-related improvements on sleep quality assessed by Pittsburgh Sleep Quality index (PSQI) (SMD = -0.50 [-0.87, -0.13], p = 0.008), wake after sleep onset (WASO) (SMD = -0.29 [-0.53, -0.05], p = 0.02) and circadian rhythm, assessed by salivary cortisol levels (MD = -0.09 (95% CI [-0.13 to -0.06]) mg/dL, p < 0.001). Results of the meta-analysis indicated that exercise had no significant effect on sleep efficiency, sleep onset latency, total sleep time and circadian rhythm assessed by accelerometry values. Conclusion: While some sleep and circadian rhythm outcomes (PSQI, WASO and salivary cortisol) exhibited significant improvements, it is still somewhat unclear what exercise prescriptions would optimize different sleep and circadian rhythm outcomes across a variety of groups of cancer survivors. Implication: As exercise does not exacerbate cancer-related circadian rhythm and sleep disturbances, and may actually produce some significant benefits, this meta-analysis provides further evidence for cancer survivors to perform regular exercise.

Quercetin improved hepatic circadian rhythm dysfunction in middle-aged mice fed with vitamin D-deficient diet

We aimed to determine whether quercetin is capable of improving circadian rhythm and metabolism disorder under vitamin D-deficient condition. Middle-aged mice were randomly divided into four groups, namely, control (CON), vitamin D-deficient diet (VDD), quercetin (Q), and quercetin intervention in vitamin D-deficient diet (VDQ), with a total of 12 weeks’ intervention. Mice were sacrificed at zeitgeber time1 (ZT1) and ZT13 time points. At ZT1, circadian locomotor output cycle kaput (CLOCK) protein expression from VDD, Q, and VDQ groups; CRY1 from Q group; and CRY2 from VDD group were significantly lower compared to CON group. The mRNA expression of Sirt1, Bmal1, Clock, Cry1, and Cry2 in VDQ groups, also Bmal1, Clock, and Cry1 from Q group, were significantly decreased compared to CON group. At ZT13, compared to CON group, fasting insulin and homeostasis model assessment-insulin resistance (HOMA-IR) were higher in VDD group; BMAL1 was significantly increased, while CLOCK and CRY1 protein were significantly decreased from VDD group; CLOCK protein from VDQ group was significantly higher compared to CON, VDD, and Q groups, and also, BMAL1 protein expression from VDQ group was elevated compared to CON group. The mRNA expression of Bmal1, Clock, Per2, Cry1, and Cry2 in VDQ groups were significantly increased compared to CON groups. The mRNA expression of Bmal1 from VDQ group was decreased compared to both VDD and Q group. In conclusion, vitamin D-deficient diet resulted in a disordered liver circadian rhythm, and quercetin improved the hepatic circadian desynchronization. Quercetin supplementation might be effective for balancing circadian rhythm under vitamin D-deficient condition. (AU)

Effects of light therapy on sleep and circadian rhythm in older type 2 diabetics living in long-term care facilities: a randomized controlled trial.

Background: Light influences the secretion of melatonin in the body and regulates circadian rhythms, which play an important role in sleep and mood. The light level of rooms in long-term care facilities is usually far below the threshold required to regulate the body's circadian rhythm, and insufficient light can easily lead to sleep and mood disturbances among older residents in nursing homes. Therefore, the objective of this study was to investigate the effects of light therapy on sleep and circadian rhythm in older adults with type 2 diabetes residing in long-term care facilities. Methods: This study was a prospective, single-blind, randomized controlled trial. Participants were randomly assigned to either the light therapy (LT) group or the control group and received the intervention for four weeks. Primary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and objective sleep parameters recorded by a sleep monitoring bracelet, Morningness-Eveningness Questionnaire (MEQ). The secondary outcome included glycated serum protein (GSP). Data was collected at three time points: at baseline (T0), immediate post-treatment (T1), and 4-week follow-up (T2). A linear mixed model analysis was used to analyzed the data. Results: We enrolled 45 long-term care residents. Compared with the control group, significant reductions in PSQI scores were observed at T1 and T2. At T2, the sleep score of objective sleep parameters was significantly higher in the LT group compared to the control group. Additionally, compared to the baseline T0, MEQ scores were significantly lower in the LT group at T1 and T2, with no significant difference in the control group. There was no significant difference between groups in glycated serum protein values at T1 and T2. However, compared to T0, glycated serum protein values decreased in the LT group while increased in the control group at T2. Conclusion: Light therapy had a positive effect on subjective sleep quality and circadian rhythm time type in long-term care residents with type 2 diabetes, and had a possible delayed effect on objective sleep. However, no discernible alterations in blood glucose levels were detected in this study.

Acupuncture Treatment for Generalized Anxiety Disorder by Activating the Vagus Nerve and Improving Heart-Rate Variability and Heart-Rhythm Coherence, A Case-Series Study.

Objective: The goal of this case series was to observe the effectiveness of acupuncture for reducing sympathetic stress and anxiety-related symptoms in generalized anxiety disorder. The effect of acupuncture on the balance of the autonomic nervous system was also examined. Materials and Methods: This was a case-series study with 10 participants enrolled. Each participant received acupuncture treatment 2 times per week for 4 weeks. Participants were evaluated with the Generalized Anxiety Disorder-7 (GAD-7) scale and the Body Perception Questionnaire-Short Form (BPQ-SF) before and after the treatment program. Heart-rate variability heart-rhythm coherence (HRC) was also assessed during each acupuncture session. Results: Five participants completed the program. Both GAD-7 and BPQ mean scores showed significant reductions. The mean HRC high-coherence ratio also increased significantly after acupuncture treatment. No adverse effects occurred. Conclusions: Acupuncture may be an effective therapy for sympathetic stress and anxiety-related symptoms. The mechanism of action may be through activating the vagus nerve and improving the HRC high coherence ratio. It is feasible to conduct larger clinical trials with random controls, longer treatment durations, and long-term follow-ups to support the results of this study.

Acupuncture in circadian rhythm sleep-wake disorders and its potential neurochemical mechanisms.

Circadian rhythm sleep-wake disorders (CRSWDs) are becoming increasingly common in modern societies due to lifestyle changes. The detrimental effects of CRSWDs on sleep and psychological health have attracted considerable attention recently. Alternative remedies for the treatment of CRSWDs have also gained attention in recent years owing to the limitations of medications. Several in vivo and clinical investigations have shown that acupuncture, one of the most important components of traditional Chinese medicine (TCM), has been shown to modulate sleep-related circadian rhythms. Owing to the lack of research on the mechanism and effectiveness of acupuncture in treating CRSWDs, clinical applications of acupuncture have not gained popularity. This paper reviews the acupuncture methods, acupoint selection, and biochemical indicators supplied by in vivo and clinical studies to explore the effectiveness of acupuncture, and summarizes the circadian rhythm mechanisms and the acupuncture characteristics on circadian rhythm. The neurochemical mechanisms linked to acupuncture in treating CRSWDs are also outlined from the perspective of the central and peripheral biological clocks. Lastly, the inadequacy of previous studies on CRSWDs and conflicting results regarding acupuncture are explored and future research directions are envisioned.

Images: "Too much heat for my non-24-hour sleep-wake disorder!" A case report.

The non-24-hour sleep-wake disorder (N24SWD) is a rare condition, sometimes associated with blindness or with suprachiasmatic nuclei lesions, resulting in a free-running rhythm or hypernycthemeral syndrome. Synchronizers, such as light, when light perception remains, melatonin, food intakes, physical activity, social interactions, and temperature, play a key role in the treatment of N24SWD. In this report, we describe a case illustrating the impact of outdoor temperature in a 34-year-old man with N24SWD effectively treated through a combination of chronotherapy interventions. During 3 consecutive heat waves, he experienced a recurrence of his natural 25.5-hour free-running rhythm, with a consistent bedtime phase delay caused by temperature, resulting in the discontinuation of chronotherapy. After these heat waves, he was able again to resynchronize his rhythms with the combination of chronotherapeutics. This case report highlights that patients with N24SWD may be particularly at risk of relapse during heat waves, with direct implications for monitoring and reinforcing chronotherapies. CITATION: Garrivet J, d'Ortho M-P, Frija-Masson J, et al. "Too much heat for my non-24-hour sleep-wake disorder!" A case report. J Clin Sleep Med. 2024;20(2):329-333.

Cellular iron depletion enhances behavioral rhythm by limiting brain Per1 expression in mice.

AIMS: Disturbances in the circadian rhythm are positively correlated with the processes of aging and related neurodegenerative diseases, which are also associated with brain iron accumulation. However, the role of brain iron in regulating the biological rhythm is poorly understood. In this study, we investigated the impact of brain iron levels on the spontaneous locomotor activity of mice with altered brain iron levels and further explored the potential mechanisms governing these effects in vitro. RESULTS: Our results revealed that conditional knockout of ferroportin 1 (Fpn1) in cerebral microvascular endothelial cells led to brain iron deficiency, subsequently resulting in enhanced locomotor activity and increased expression of clock genes, including the circadian locomotor output cycles kaput protein (Clock) and brain and muscle ARNT-like 1 (Bmal1). Concomitantly, the levels of period circadian regulator 1 (PER1), which functions as a transcriptional repressor in regulating biological rhythm, were decreased. Conversely, the elevated brain iron levels in APP/PS1 mice inhibited autonomous rhythmic activity. Additionally, our findings demonstrate a significant decrease in serum melatonin levels in Fpn1cdh5 -CKO mice compared with the Fpn1flox/flox group. In contrast, APP/PS1 mice with brain iron deposition exhibited higher serum melatonin levels than the WT group. Furthermore, in the human glioma cell line, U251, we observed reduced PER1 expression upon iron limitation by deferoxamine (DFO; iron chelator) or endogenous overexpression of FPN1. When U251 cells were made iron-replete by supplementation with ferric ammonium citrate (FAC) or increased iron import through transferrin receptor 1 (TfR1) overexpression, PER1 protein levels were increased. Additionally, we obtained similar results to U251 cells in mouse cerebellar astrocytes (MA-c), where we collected cells at different time points to investigate the rhythmic expression of core clock genes and the impact of DFO or FAC treatment on PER1 protein levels. CONCLUSION: These findings collectively suggest that altered iron levels influence the circadian rhythm by regulating PER1 expression and thereby modulating the molecular circadian clock. In conclusion, our study identifies the regulation of brain iron levels as a potential new target for treating age-related disruptions in the circadian rhythm.

Managing non-24-hour sleep-wake rhythm disorder with ramelteon in a 12-year-old girl with Pierre Robin sequence and developmental delay: a case report.

The author recently observed a case involving a 12-year-old sighted girl who exhibited symptoms typical of non-24-hour sleep-wake rhythm disorder (N24SWD). This disorder, more commonly found in blind individuals, presents a unique challenge when diagnosed in those with vision. Several interventions can be attempted, ranging from behavioral adjustments to light therapy. Although melatonin has been noted for its effectiveness in realigning the patient's sleep-wake cycle, the use of ramelteon, a melatonin receptor agonist, has seldom been reported in managing N24SWD. However, this case illuminates the potential of ramelteon as another therapeutic option for sighted individuals with N24SWD. Further study is suggested to determine the potential of ramelteon in managing this disorder among sighted individuals of varying age groups. CITATION: Huang C-H. Managing non-24-hour sleep-wake rhythm disorder with ramelteon in a 12-year-old girl with Pierre Robin sequence and developmental delay: a case report. J Clin Sleep Med. 2024;20(6):995-997.

Differential Response of MYB Transcription Factor Gene Transcripts to Circadian Rhythm in Tea Plants (Camellia sinensis).

The circadian clock refers to the formation of a certain rule in the long-term evolution of an organism, which is an invisible 'clock' in the body of an organism. As one of the largest TF families in higher plants, the MYB transcription factor is involved in plant growth and development. MYB is also inextricably correlated with the circadian rhythm. In this study, the transcriptome data of the tea plant 'Baiyeyihao' were measured at a photoperiod interval of 4 h (24 h). A total of 25,306 unigenes were obtained, including 14,615 unigenes that were annotated across 20 functional categories within the GO classification. Additionally, 10,443 single-gene clusters were annotated to 11 sublevels of metabolic pathways using KEGG. Based on the results of gene annotation and differential gene transcript analysis, 22 genes encoding MYB transcription factors were identified. The G10 group in the phylogenetic tree had 13 members, of which 5 were related to the circadian rhythm, accounting for 39%. The G1, G2, G8, G9, G15, G16, G18, G19, G20, G21 and G23 groups had no members associated with the circadian rhythm. Among the 22 differentially expressed MYB transcription factors, 3 members of LHY, RVE1 and RVE8 were core circadian rhythm genes belonging to the G10, G12 and G10 groups, respectively. Real-time fluorescence quantitative PCR was used to detect and validate the expression of the gene transcripts encoding MYB transcription factors associated with the circadian rhythm.

Autonomic nervous system responses in the intermediate band to cranial cutaneous stimulation.

Cardiovascular rhythms representing functional states of the autonomic nervous system (ANS) are insufficiently reflected by the current physiological model based on low and high frequency bands (LF, HF, resp.). An intermediate (IM) frequency band generated by a brainstem pacemaker was included in systemic physiological ANS analyses of forehead skin perfusion (SP), ECG, and respiration. Data of 38 healthy participants at T0 and T1 (+1 week) before, during, and following osteopathic cranial vault hold (CVH) stimulation were analyzed including momentary frequencies of highest amplitude, amplitudes in low (0.05-0.12 Hz), IM (0.12-0.18 Hz), and high (0.18-0.4 Hz) frequency bands, and established heart rate variability (HRV) metrics. During CVH, LF interval durations increased, whereas IM/HF band durations decreased significantly. Amplitudes increased significantly in all frequency bands. A cluster analysis found one response pattern dominated by IM activity (47% of participants) with highly stable 0.08 Hz oscillation to CVH, and one dominated by LF activity (0.10 Hz) at T0, increasing to IM activity at T1. Showing frequency ratios at ≈3:1, respiration was not responsible for oscillations in PPG during CVH. HRV revealed no significant responses. Rhythmic patterns in SP and respiration matched previous findings on a reticular "0.15 Hz rhythm". Involvement of baroreflex pathways is discussed as alternative explanation.

Registry and survey of circadian rhythm sleep-wake disorder patients.

Objective: Circadian Sleep Disorders Network has created a registry of circadian rhythm sleep-wake disorder (CRSWD) patients, and a survey of their experiences. The purpose of the registry is to provide volunteers willing to participate in research; the purpose of the survey is to fill some of the knowledge gaps on these disorders, including information on subjective patient experience and the efficacy and durability of treatments.Researchers are invited to contact Circadian Sleep Disorders Network for permission to use the registry to find potential research participants, and to further analyze the survey data. Patients: Over 1627 patients have participated; 1298 have completed the entire survey. Here we present results based on the 479 clinically diagnosed CRSWD patients. Methods: The survey covers a variety of topics relating to CRSWDs, including diagnosis, comorbidities, treatments, and work/educational accommodations. Conclusions: Results of this survey diverged from much of the literature. More than half the participants reported tiredness even when sleeping on their preferred schedule. While depression may cause sleep problems, our data suggests that sleep/circadian problems often precede depression.There were more people suffering from sighted non-24-hour sleep-wake rhythm disorder than some of the literature would lead us to expect.Current treatments did not appear to be helpful to a large percentage of our participants. Most of them did not find light therapy helpful and nearly all participants who tried phase-delay chronotherapy reported at best only short-term improvement. A sizable proportion of people who tried phase-delay chronotherapy subsequently developed non-24-hour sleep-wake rhythm disorder.