Olfactory Bulbectomy Impedes Social but Not Photic Reentrainment of Circadian Rhythms in Female Octodon degus

Recent studies demonstrated that nonphotic (social) cues markedly accelerate reentrainment to large phase shifts of the light-dark (LD) cycle in female Octodon degus and that such changes are likely effected by chemosensory stimuli. This experiment investigated the effects of olfactory bulbectomies on (1) socially facilitated reentrainment rates of circadian rhythms following a 6-h phase advance of the LD cycle, (2) photic reentrainment rates of circadian rhythms following a 6-h advance of the LD cycle, (3) photic entrainment, and (4) the circadian period (τ) of activity rhythms in constant darkness (DD). Olfactory bulbectomies (BX) blocked socially facilitated reentrainment rates but did not alter reentrainment rates of circadian rhythms to photic cues alone. In addition, BX lowered mean daily locomotor activity levels and decreased the amplitude of the activity rhythm in degus housed in entrained (LD 12:12) conditions but did not alter the phase of activity onset or offset, duration (α) of activity, or mean daily core body temperature. Bulbectomies also failed to modify τ of free-running activity rhythms. This experiment confirms that the olfactory bulbs and che mosensory cues are necessary for socially facilitated reentrainment. In contrast to their effects in nocturnal rodents, BX do not produce significant circadian photic changes in diurnal degus. This is the first experiment to determine that chemosensory stimuli modulate the circadian system in a diurnal rodent.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66499/2/10.1177_074873049701200408.pd

Sex differences and effects of social cues on daily rhythms following phase advances in Octodon degus

Two experiments were designed to determine whether social cues could enhance the rate of resynchronization in body temperature and general activity rhythms in male or female Octodon degus following a 6 h phase advance. The first experiment examined average resynchronization rates for animals in each condition. The second experiment examined resynchronization rates for a smaller group of animals, each treated as its own control. Female phase-shifters resynchronized temperature and activity rhythms significantly faster when housed with an entrained (donor) female than those females housed with another phase-shifting female or housed alone. Females housed with entrained males resynchronized their temperature rhythms significantly slower than females housed with entrained females. No differences in resynchronization rate for phase-shifting males existed between test conditions. However, activity rhythms of male controls (housed alone) reentrained significantly faster than those of female controls. These experiments demonstrate a sex difference in (i) reentrainment rate by photic cues alone; (ii) donors' effect on female phase-shifters' resynchronization; and (iii) phase-shifters' resynchronization response to donor cues. In these studies, resynchronization in the presence of another animal could either have been achieved by entrainment of the pacemaker or by masking of the circadian rhythms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60641/1/sex_differences.pd

PER3 Polymorphism Predicts Cumulative Sleep Homeostatic but Not Neurobehavioral Changes to Chronic Partial Sleep Deprivation

The variable number tandem repeat (VNTR) polymorphism 5-repeat allele of the circadian gene PERIOD3 (PER3(5/5)) has been associated with cognitive decline at a specific circadian phase in response to a night of total sleep deprivation (TSD), relative to the 4-repeat allele (PER3(4/4)). PER3(5/5) has also been related to higher sleep homeostasis, which is thought to underlie this cognitive vulnerability. To date, no study has used a candidate gene approach to investigate the response to chronic partial sleep deprivation (PSD), a condition distinct from TSD and one commonly experienced by millions of people on a daily and persistent basis. We evaluated whether the PER3 VNTR polymorphism contributed to cumulative neurobehavioral deficits and sleep homeostatic responses during PSD.PER3(5/5) (n = 14), PER3(4/5) (n = 63) and PER3(4/4) (n = 52) healthy adults (aged 22-45 y) demonstrated large, but equivalent cumulative decreases in cognitive performance and physiological alertness, and cumulative increases in sleepiness across 5 nights of sleep restricted to 4 h per night. Such effects were accompanied by increasing daily inter-subject variability in all groups. The PER3 genotypes did not differ significantly at baseline in habitual sleep, physiological sleep structure, circadian phase, physiological sleepiness, cognitive performance, or subjective sleepiness, although during PSD, PER3(5/5) subjects had slightly but reliably elevated sleep homeostatic pressure as measured physiologically by EEG slow-wave energy in non-rapid eye movement sleep compared with PER3(4/4) subjects. PER3 genotypic and allelic frequencies did not differ significantly between Caucasians and African Americans.The PER3 VNTR polymorphism was not associated with individual differences in neurobehavioral responses to PSD, although it was related to one marker of sleep homoeostatic response during PSD. The comparability of PER3 genotypes at baseline and their equivalent inter-individual vulnerability to sleep restriction indicate that PER3 does not contribute to the neurobehavioral effects of chronic sleep loss

Cardiovascular measures display robust phenotypic stability across long-duration intervals involving repeated sleep deprivation and recovery

IntroductionWe determined whether cardiovascular (CV) measures show trait-like responses after repeated total sleep deprivation (TSD), baseline (BL) and recovery (REC) exposures in two long-duration studies (total N = 11 adults).MethodsA 5-day experiment was conducted twice at months 2 and 4 in a 4-month study (N = 6 healthy adults; 3 females; mean age ± SD, 34.3 ± 5.7 years; mean BMI ± SD, 22.5 ± 3.2 kg/m2), and three times at months 2, 4, and 8 in an 8-month study (N = 5 healthy adults; 2 females; mean age ± SD, 33.6 ± 5.17 years; mean BMI ± SD, 27.1 ± 4.9 kg/m2). Participants were not shift workers or exposed to TSD in their professions. During each experiment, various seated and standing CV measures were collected via echocardiography [stroke volume (SV), heart rate (HR), cardiac index (CI), left ventricular ejection time (LVET), and systemic vascular resistance index (SVRI)] or blood pressure monitor [systolic blood pressure (SBP)] after (1) two BL 8h time in bed (TIB) nights; (2) an acute TSD night; and (3) two REC 8–10 h TIB nights. Intraclass correlation coefficients (ICCs) assessed CV measure stability during BL, TSD, and REC and for the BL and REC average (BL + REC) across months 2, 4, and 8; Spearman’s rho assessed the relative rank of individuals’ CV responses across measures.ResultsSeated BL (0.693–0.944), TSD (0.643–0.962) and REC (0.735–0.960) CV ICCs showed substantial to almost perfect stability and seated BL + REC CV ICCs (0.552–0.965) showed moderate to almost perfect stability across months 2, 4, and 8. Individuals also exhibited significant, consistent responses within seated CV measures during BL, TSD, and REC. Standing CV measures showed similar ICCs for BL, TSD, and REC and similar response consistency.DiscussionThis is the first demonstration of remarkably robust phenotypic stability of a number of CV measures in healthy adults during repeated TSD, BL and REC exposures across 2, 4, and 8 months, with significant consistency of responses within CV measures. The cardiovascular measures examined in our studies, including SV, HR, CI, LVET, SVRI, and SBP, are useful biomarkers that effectively track physiology consistently across long durations and repeated sleep deprivation and recovery

Characterizing Glycemic Control and Sleep in Adults with Long-Standing Type 1 Diabetes and Hypoglycemia Unawareness Initiating Hybrid Closed Loop Insulin Delivery

Nocturnal hypoglycemia is life threatening for individuals with type 1 diabetes (T1D) due to loss of hypoglycemia symptom recognition (hypoglycemia unawareness) and impaired glucose counter regulation. These individuals also show disturbed sleep, which may result from glycemic dysregulation. Whether use of a hybrid closed loop (HCL) insulin delivery system with integrated continuous glucose monitoring (CGM) designed for improving glycemic control, relates to better sleep across time in this population remains unknown. The purpose of this study was to describe long-term changes in glycemic control and objective sleep after initiating hybrid closed loop (HCL) insulin delivery in adults with type 1 diabetes and hypoglycemia unawareness. To accomplish this, six adults (median age = 58 y) participated in an 18-month ongoing trial assessing HCL effectiveness. Glycemic control and sleep were measured using continuous glucose monitoring and wrist accelerometers every 3 months. Paired sample t-tests and Cohen’s d effect sizes modeled glycemic and sleep changes and the magnitude of these changes from baseline to 9 months. Reduced hypoglycemia (d = 0:47‐0:79), reduced basal insulin requirements (d = 0:48), and a smaller glucose coefficient of variation (d = 0:47) occurred with medium-large effect sizes from baseline to 9 months. Hypoglycemia awareness improved from baseline to 6 months with medium-large effect sizes (Clarke score (d = 0:60), lability index (d = 0:50), HYPO score (d = 1:06)). Shorter sleep onset latency (d = 1:53; p \u3c 0:01), shorter sleep duration (d = 0:79), fewer total activity counts (d = 1:32), shorter average awakening length (d = 0:46), and delays in sleep onset (d = 1:06) and sleep midpoint (d = 0:72) occurred with medium-large effect sizes from baseline to 9 months. HCL led to clinically significant reductions in hypoglycemia and improved hypoglycemia awareness. Sleep showed a delayed onset, reduced awakening length and onset latency, and maintenance of high sleep efficiency after initiating HCL. Our findings add to the limited evidence on the relationships between diabetes therapeutic technologies and sleep health. This trial is registered with ClinicalTrials.gov (NCT03215914)

Keeping an Eye on Circadian Time in Clinical Research and Medicine

Background: Daily rhythms are observed in humans and almost all other organisms. Most of these observed rhythms reflect both underlying endogenous circadian rhythms and evoked responses from behaviours such as sleep/wake, eating/fasting, rest/activity, posture changes and exercise. For many research and clinical purposes, it is important to understand the contribution of the endogenous circadian component to these observed rhythms. Content: The goal of this manuscript is to provide guidance on best practices in measuring metrics of endogenous circadian rhythms in humans and promote the inclusion of circadian rhythms assessments in studies of health and disease. Circadian rhythms affect all aspects of physiology. By specifying minimal experimental conditions for studies, we aim to improve the quality, reliability and interpretability of research into circadian and daily (i.e., time-of-day) rhythms and facilitate the interpretation of clinical and translational findings within the context of human circadian rhythms. We describe protocols, variables and analyses commonly used for studying human daily rhythms, including how to assess the relative contributions of the endogenous circadian system and other daily patterns in behaviours or the environment. We conclude with recommendations for protocols, variables, analyses, definitions and examples of circadian terminology.Conclusion: Although circadian rhythms and daily effects on health outcomes can be challenging to distinguish in practice, this distinction may be important in many clinical settings. Identifying and targeting the appropriate underlying (patho)physiology is a medical goal. This review provides methods for identifying circadian effects to aid in the interpretation of published work and the inclusion of circadian factors in clinical research and practice

Catechol-O-Methyltransferase Val158Met Polymorphism Associates with Individual Differences in Sleep Physiologic Responses to Chronic Sleep Loss

Val158Met polymorphism was a novel marker in healthy adults of differential vulnerability to chronic partial sleep deprivation (PSD), a condition distinct from total sleep loss and one experienced by millions on a daily and persistent basis. allelic frequencies were higher in whites than African Americans.-related treatment responses and risk factors for symptom exacerbation

Increased Sleep Fragmentation Leads to Impaired Off-Line Consolidation of Motor Memories in Humans

A growing literature supports a role for sleep after training in long-term memory consolidation and enhancement. Consequently, interrupted sleep should result in cognitive deficits. Recent evidence from an animal study indeed showed that optimal memory consolidation during sleep requires a certain amount of uninterrupted sleep