Phase Of Rhythm Research Articles

A state space modeling approach to real-time phase estimation.

Brain rhythms have been proposed to facilitate brain function, with an especially important role attributed to the phase of low-frequency rhythms. Understanding the role of phase in neural function requires interventions that perturb neural activity at a target phase, necessitating estimation of phase in real-time. Current methods for real-time phase estimation rely on bandpass filtering, which assumes narrowband signals and couples the signal and noise in the phase estimate, adding noise to the phase and impairing detections of relationships between phase and behavior. To address this, we propose a state space phase estimator for real-time tracking of phase. By tracking the analytic signal as a latent state, this framework avoids the requirement of bandpass filtering, separately models the signal and the noise, accounts for rhythmic confounds, and provides credible intervals for the phase estimate. We demonstrate in simulations that the state space phase estimator outperforms current state-of-the-art real-time methods in the contexts of common confounds such as broadband rhythms, phase resets, and co-occurring rhythms. Finally, we show applications of this approach to in vivo data. The method is available as a ready-to-use plug-in for the Open Ephys acquisition system, making it widely available for use in experiments.

Mechanisms of Flexible Information Sharing through Noisy Oscillations.

Simple SummaryTo properly interact with our environment, the brain must be able to identify external stimuli, process them, and make the right decisions all in a short time. This may involve several brain regions interacting together by sharing information birectionally via rhythmic activity. Such flexibility requires the functional connectivity between the areas to be dynamic, and a key question is the relevant parameter and operating regimes that make this possible in spite of fixed structural connectivity. Working towards this goal, we consider two coupled brain regions, each of which exhibits a noisy rhythm, a commonly observed type of neural activity. Such rhythms can be induced by the stochasticity in the neural circuitry, or be autonomously generated through nonlinearities and not necessitating noise. For these two types of rhythms, we computed the amount of information shared between the brain areas and the preferred direction(s) of sharing. We found that without the coupling delay, the flexibility needed by the brain to perform cognitive tasks requires the rhythms to be autogenerated rather than noise-induced. This is the case even with asymmetry or heterogeneity. This suggests that the importance of the dynamical regime has to be taken into account when modeling interacting neural rhythms from an information theoretical point of view.Brain areas must be able to interact and share information in a time-varying, dynamic manner on a fast timescale. Such flexibility in information sharing has been linked to the synchronization of rhythm phases between areas. One definition of flexibility is the number of local maxima in the delayed mutual information curve between two connected areas. However, the precise relationship between phase synchronization and information sharing is not clear, nor is the flexibility in the face of the fixed structural connectivity and noise. Here, we consider two coupled oscillatory excitatory-inhibitory networks connected through zero-delay excitatory connections, each of which mimics a rhythmic brain area. We numerically compute phase-locking and delayed mutual information between the phases of excitatory local field potential (LFPs) of the two networks, which measures the shared information and its direction. The flexibility in information sharing is shown to depend on the dynamical origin of oscillations, and its properties in different regimes are found to persist in the presence of asymmetry in the connectivity as well as system heterogeneity. For coupled noise-induced rhythms (quasi-cycles), phase synchronization is robust even in the presence of asymmetry and heterogeneity. However, they do not show flexibility, in contrast to noise-perturbed rhythms (noisy limit cycles), which are shown here to exhibit two local information maxima, i.e., flexibility. For quasi-cycles, phase difference and information measures for the envelope-phase dynamics obtained from previous analytical work using the Stochastic Averaging Method (SAM) are found to be in good qualitative agreement with those obtained from the original dynamics. The relation between phase synchronization and communication patterns is not trivial, particularly in the noisy limit cycle regime. There, complex patterns of information sharing can be observed for a single value of the phase difference. The mechanisms reported here can be extended to I-I networks since their phase synchronizations are similar. Our results set the stage for investigating information sharing between several connected noisy rhythms in neural and other complex biological networks.

Modeling the Influence of Chronic Sleep Restriction on Cortisol Circadian Rhythms, with Implications for Metabolic Disorders.

Chronic sleep deficiency is prevalent in modern society and is associated with increased risk of metabolic and other diseases. While the mechanisms by which chronic sleep deficiency induces pathophysiological changes are yet to be elucidated, the hypothalamic–pituitary–adrenal (HPA) axis may be an important mediator of these effects. Cortisol, the primary hormone of the HPA axis, exhibits robust circadian rhythmicity and is moderately influenced by sleep and wake states and other physiology. Several studies have explored the effects of acute or chronic sleep deficiency (i.e., usually from self-selected chronic sleep restriction, CSR) on the HPA axis. Quantifying long-term changes in the circadian rhythm of cortisol under CSR in controlled conditions is inadequately studied due to practical limitations. We use a semi-mechanistic mathematical model of the HPA axis and the sleep/wake cycle to explore the influence of CSR on cortisol circadian rhythmicity. In qualitative agreement with experimental findings, model simulations predict that CSR results in physiologically relevant disruptions in the phase and amplitude of the cortisol rhythm. The mathematical model presented in this work provides a mechanistic framework to further explore how CSR might lead to HPA axis disruption and subsequent development of chronic metabolic complications.

Alpha and high gamma phase amplitude coupling during motor imagery and weighted cross-frequency coupling to extract discriminative cross-frequency patterns

Motor imagery modulates specific neural oscillations like actual movement does. Representatively, suppression of the alpha power (e.g., event-related desynchronization [ERD]) is the typical pattern of motor imagery in the motor cortex. However, in addition to this amplitude-based feature, the coupling across frequencies includes important information about the brain functions and the existence of such complex information has been reported in various invasive studies. Yet, the interaction across multiple frequencies during motor imagery processing is still unclear and has not been widely studied, particularly concerning the non-invasive signals. In this study, we provide empirical evidence of the comodulation between the phase of alpha rhythm and the amplitude of high gamma rhythm during the motor imagery process. We used electroencephalography (EEG) in our investigation during the imagination of left- or right-hand movement recorded from 52 healthy subjects, and quantified the ERD of alpha and phase-amplitude coupling (PAC) which is a relative change of modulation index to the base line period (before the cue). As a result, we found that the coupling between the phase of alpha (8–12 Hz) and the amplitude of high gamma (70–120 Hz) and this PAC decreases during motor imagery and then rebounds to the baseline like alpha ERD (r = 0.29 to 0.42). This correlation between PAC and ERD was particularly stronger in the ipsilateral area. In addition, trials that demonstrated higher alpha power during the ready period (before the cue) showed a larger ERD during motor imagery and similarly, trials with higher modulation index during the ready period yielded a greater decrease in PAC during imagery. In the classification analysis, we found that the effective phase frequency that showed better decoding accuracy in left and right-hand imagery, varied across subjects. Motivated by result, we proposed a weighted cross-frequency coupling (WCFC) method that extracts the maximal discriminative feature by combining band power and CFC. In the evaluation, WCFC with only two electrodes yielded a performance comparable to the conventional algorithm with 64 electrodes in classifying left and right-hand motor imagery. These results indicate that the phase-amplitude frequency plays an important role in motor imagery, and that optimizing this frequency ranges is crucial for extracting information features to decode the motor imagery types.

Changes in Body Temperature of Small Mammals and Birds in a Few Minutes Range as Reflection of Environmental Influences.

The study examined the changes in intraperitoneal body temperature of laboratory mice, Jungar hamsters, European greenfinch Chloris chloris, and starlings. In a few minutes range, these changes significantly correlated not only between the animals of the same species, but also between the different classes such as birds and mammals, which were isolated from each other and maintained under different illumination regimen. This phenomenon indicates some external influence(s) on the central mechanisms of the thermal control system not related to illumination regiment. In 80% cases, the phases of most pronounced rhythms of body temperature oscillating with the periods of 8-9 and 12-13 min coincided with those of geomagnetic field within the accuracy of ±1 min. However, the amplitude of body temperature oscillations did not depend on the amplitude of geomagnetic field (GMF) oscillations. Synchronicity of the changes in body temperature and GMF was observed at the amplitude of GMF oscillation of 0.4 nT, which is extremely low value. In contrast, there was no reaction of body temperature to greater (6-10 nT) but irregular and abrupt perturbations of GMF.

Reversible modulation of circadian time with chronophotopharmacology

The circadian clock controls daily rhythms of physiological processes. The presence of the clock mechanism throughout the body is hampering its local regulation by small molecules. A photoresponsive clock modulator would enable precise and reversible regulation of circadian rhythms using light as a bio-orthogonal external stimulus. Here we show, through judicious molecular design and state-of-the-art photopharmacological tools, the development of a visible light-responsive inhibitor of casein kinase I (CKI) that controls the period and phase of cellular and tissue circadian rhythms in a reversible manner. The dark isomer of photoswitchable inhibitor 9 exhibits almost identical affinity towards the CKIα and CKIδ isoforms, while upon irradiation it becomes more selective towards CKIδ, revealing the higher importance of CKIδ in the period regulation. Our studies enable long-term regulation of CKI activity in cells for multiple days and show the reversible modulation of circadian rhythms with a several hour period and phase change through chronophotopharmacology.

The Role of Colony Temperature in the Entrainment of Circadian Rhythms of Honey Bee Foragers.

Honey bees utilize their circadian rhythms to accurately predict the time of day. This ability allows foragers to remember the specific timing of food availability and its location for several days. Previous studies have provided strong evidence toward light/dark cycles being the primary Zeitgeber for honey bees. Work in our laboratory described large individual variation in the endogenous period length of honey bee foragers from the same colony and differences in the endogenous rhythms under different constant temperatures. In this study, we further this work by examining the temperature inside the honey bee colony. By placing temperature and light data loggers at different locations inside the colony we measured temperature at various locations within the colony. We observed significant oscillations of the temperature inside the hive, that show seasonal patterns. We then simulated the observed temperature oscillations in the laboratory and found that using the temperature cycle as a Zeitgeber, foragers present large individual differences in the phase of locomotor rhythms for temperature. Moreover, foragers successfully synchronize their locomotor rhythms to these simulated temperature cycles. Advancing the cycle by six hours, resulting in changes in the phase of activity in some foragers in the assay. The results are shown in this study highlight the importance of temperature as a potential Zeitgeber in the field. Future studies will examine the possible functional and evolutionary role of the observed phase differences of circadian rhythms.

045 Associations of Actigraphic Sleep and Circadian Rest/Activity Rhythms with Cognition in the Early Phase of Alzheimer’s Disease

Abstract Introduction Alterations in sleep and circadian rhythms are common in persons with Alzheimer’s disease (AD) dementia, but the nature of such changes in the early phases of AD remains unclear. This study compared sleep and circadian rest/activity rhythms (RARs), measured by standard and novel actigraphic indices, between participants with normal cognition or mild cognitive impairment (MCI), and examined cross-sectional associations between these measures and cognition. Methods Actigraphy data were collected in 179 individuals (mean age=72.6 years, gender=64.8% female) with normal cognition (n=153) or MCI (n=26) from the Biomarkers for Older Controls at Risk of Dementia (BIOCARD) study. Standard sleep parameters (i.e., total sleep time [TST], sleep efficiency [SE], wake after sleep onset [WASO], average wake bout length [WBL]), and standard non-parametric RAR metrics (i.e., relative amplitude [RA], intradaily variability [IV], interdaily stability [IS]) were generated. Functional principal component (fPC) methods were used to generate three novel RAR indices (fPC1, fPC2, fPC3) representing 69% of the total variance. Cognitive test scores were used to generate composite measures reflecting the domains of episodic memory and executive function using factor analysis. Regression models were used to compare sleep and circadian RAR parameters between the diagnostic groups and to evaluate their associations with cognitive performance. Results After adjustment for age, sex, education, and APOE-4 genotype, compared to normal controls, MCI subjects had significantly lower SE, lower RA, and lower scores on the novel RAR measure fPC3, which reflects a later rhythm phase, lower amplitude, and lower activity both at night and early in the day. In analyses combining data from participants with MCI and controls, several standard RAR parameters (e.g., higher RA and IS) and higher fPC3 scores were associated with both better episodic memory and executive function. Additionally, several standard measures (e.g., lower WASO and IV) and lower fPC1 scores (reflecting higher rhythm amplitude and greater activity throughout daytime hours) were linked with better executive function. Conclusion MCI participants have sleep and circadian alterations, which are significantly associated with cognitive performance. A novel RAR measure, fPC3, showed differences in rhythm patterns that extended from the night into the daytime. Support (if any) Funding-support NIA (U19-AG033655, T32-AG027668, R01-AG050507) and AASMF (#223-BS-19).

758 Circadian rest-activity signatures in women with major depressive disorder

Abstract Introduction Patients with major depressive disorder (MDD) show disrupted circadian rhythms and sleep, including reduced daytime physical activity and poor sleep quality. However, previous findings are masked by psychotropic medication intake, co-morbid diseases and years of chronic mental illness. Here, we aim at identifying circadian motor activity patterns in unmedicated women at the onset of MDD. Methods Twelve young unmedicated women with MDD (Mean+-SD: 24.9+-5.2y; range: 18-33y) and eight age-matched healthy women (Mean+-SD: 24.5+-3.2y; range: 20-31y) participated in our study. Activity recordings were collected using wrist-worn wearable devices (actigraphs) for ~7 days in real-life settings. Cosinor analyses were performed to assess the amplitude and phase of the 24-h rest-activity activity rhythms. Non-parametric analyses were used to quantify interdaily stability and intradaily variability of the rest-activity rhythm. Furthermore, we calculated the mean activity level and scaling exponent alpha, which quantifies the temporal correlation in activity fluctuations, per 3-h bins across the 24-h sleep-wake cycle. Results Women with MDD showed a significantly higher amplitude of the 24-h rest-activity activity rhythm (Mean+-SD: 332.7+-120.8 arbitrary units) than the controls (179.7+-122.9; p=0.002), elicited by higher activity levels during the daytime (0-12h after habitual wake-up time; p<0.01). In contrast, women with MDD showed a trend for lower interdaily stability levels than controls (respectively, 0.41+-0.07 and 0.46+-0.08; p=0.05). Interestingly, a significant interaction effect of “group” and “time since habitual wake” was elicited for scaling exponent alpha (p<0.001). Accordingly, women with MDD had higher alpha values during habitual sleep (0–6 hours before habitual wake-up time) than controls (respectively, 1.18+-0.22 and 1.12+-0.22). Conclusion Unmedicated women at the onset of MDD had altered circadian motor activity patterns, as indexed by higher amplitude particularly during daytime while awake, less stable 24-h activity rhythms, and highly correlated activity patterns during sleep that closely resemble those typically occurring during wakefulness. These findings suggest that MDD per se may be associated with impaired rest-activity profiles. Ultimately, the use of wearable devices might hold important prospects for the early detection of individuals at risk for mood disorders. Support (if any) Swiss National Science Foundation Grants START #3100–055385.98, 3130-0544991.98 and 320000-108108; NIH RF1AG064312, RF1AG059867

Optogenetic manipulations of preBӧtC Oprm1 expressing neurons reveal dual mechanisms of opioid‐induced respiratory depression

The analgesic utility of opioid-based drugs is limited by the risk of adverse and life-threatening side effects, including respiratory depression. Opioid-induced respiratory depression (OIRD) is characterized by a pronounced decrease in the frequency and regularity of inspiratory efforts. The inspiratory rhythm originates from the preBötzinger Complex (preBӧtC), a network of interconnected neurons located bilaterally in the ventral medulla. At the network level, the frequency and regularity of the inspiratory rhythm is primarily determined by the inter-burst interval (IBI) which is regulated, in part, by pre-inspiratory spiking activity of excitatory preBötC neurons. To shed light on the cellular- and network-level consequences of μ-opioid receptor (MOR) activation in the preBötC, we utilized Oprm1Cre mice to optogenetically identify and manipulate MOR expressing neurons. We found that ~50% of functionally identified preBӧtC neurons express Oprm1, and Oprm1 expression is distributed evenly among neurons with pre-inspiratory, inspiratory, expiratory, and tonic discharge identities. Patch clamp recordings revealed that MOR activation reduces spiking of Oprm1+ pre-inspiratory neurons preferentially between inspiratory bursts during the percolation phase of the inspiratory rhythm, with a more modest suppression of spiking activity during inspiratory bursts. These changes at the single-cell level were manifested at the level of the preBӧtC network as a decrease in the total integrated spiking activity during the IBI and an increase in the probability of burst failures. However, in both rhythmic brainstem slices and anesthetized adult mice, optogenetic hyperpolarization of preBӧtC Oprm1+ neurons to mimic the changes in spiking activity induced by MOR activation did not phenocopy OIRD. In addition to changes in spiking activity, we found that MOR activation reduces the efficacy of excitatory synaptic transmission from Oprm1+ neurons to their post-synaptic targets by ~50%. This synaptic effect of MOR activation limits the ability of Oprm1+ preBӧtC neurons to drive the inspiratory rhythm. Based on these results in vitro and in vivo, we constructed a computational network in silico to model the effects of MOR activation on preBötC rhythmogenesis. Using this in silico model, we included subpopulation of Oprm1+ model neurons and tested the functional consequences of 1) hyperpolarization to suppress spiking vs. 2) suppression of synaptic transmission. By manipulating these mechanisms independently or in combination, we find that these dual mechanisms of opioid action act synergistically to make a normally robust inspiratory rhythm generating network particularly prone to collapse when challenged with exogenous opioids.

Relationship between circadian rhythm and brain cognitive functions.

Circadian rhythms are considered a masterstroke of natural selection, which gradually increase the adaptability of species to the Earth's rotation. Importantly, the nervous system plays a key role in allowing organisms to maintain circadian rhythmicity. Circadian rhythms affect multiple aspects of cognitive functions (mainly via arousal), particularly those needed for effort-intensive cognitive tasks, which require considerable top-down executive control. These include inhibitory control, working memory, task switching, and psychomotor vigilance. This mini review highlights the recent advances in cognitive functioning in the optical and multimodal neuroimaging fields; it discusses the processing of brain cognitive functions during the circadian rhythm phase and the effects of the circadian rhythm on the cognitive component of the brain and the brain circuit supporting cognition.

Hormonal fine-tuning of clock in decidual region of mouse placenta by dopamine, melatonin, insulin, leptin and ghrelin

IntroductionThe maternal part of the rodent placenta harbors a circadian clock which robustly responds to glucocorticoids, however, its sensitivity to other hormones has not been elucidated. In this study, we tested five selected hormones (dopamine, melatonin, insulin, leptin and ghrelin) for their effectiveness to affect the clock in decidual region of mouse placenta in vitro. MethodsWe administered the hormones or corresponding vehicles at various time points over 24 h to organotypic placental explants of mPer2Luc mice containing the decidua basalis (DB) region and monitored their effects on amplitude, period, median expression level (mesor) and phase of PER2-driven bioluminescence rhythms. ResultsDopamine significantly increased the amplitude, robustly dampened the mesor, and during a narrow time interval (corresponding to daytime) induced phase delays of the rhythms. In contrast, melatonin had no effect on amplitude, but induced phase advances of the rhythms at the opposite time window than dopamine (corresponding to nighttime). Leptin and ghrelin, but not insulin, slightly increased amplitudes and moderately modulated phase delays of the clock, suggesting that the DB clock, in contrast to other peripheral clocks, is rather resilient to abrupt changes in levels of feeding- and metabolism-related hormones. DiscussionThe results demonstrate for the first time that dopamine and melatonin exhibit delicate yet specific effects on parameters of the DB clock and may thus potentially contribute to fine-tuning of its phase under in vivo conditions. It also implies that dysregulation of their levels, which accompany various pathologies, may account for malfunction of the clock in DB.

Children with autism spectrum disorder show altered functional connectivity and abnormal maturation trajectories in response to inverted faces.

The processing of information conveyed by faces is a critical component of social communication. While the neurophysiology of processing upright faces has been studied extensively in autism spectrum disorder (ASD), less is known about the neurophysiological abnormalities associated with processing inverted faces in ASD. We used magnetoencephalography (MEG) to study both long-range and local functional connectivity, with the latter assessed using local cross-frequency coupling, in response to inverted faces stimuli, in 7-18 years old individuals with ASD and age and IQ matched typically developing (TD) individuals. We found abnormally reduced coupling between the phase of the alpha rhythm and the amplitude of the gamma rhythm in the fusiform face area (FFA) in response to inverted faces, as well as reduced long-range functional connectivity between the FFA and the inferior frontal gyrus (IFG) in response to inverted faces in the ASD group. These group differences were absent in response to upright faces. The magnitude of functional connectivity between the FFA and the IFG was significantly correlated with the severity of ASD, and FFA-IFG long-range functional connectivity increased with age in TD group, but not in the ASD group. Our findings suggest that both local and long-range functional connectivity are abnormally reduced in children with ASD when processing inverted faces, and that the pattern of abnormalities associated with the processing of inverted faces differs from the pattern of upright faces in ASD, likely due to the presumed greater reliance on top-down regulations necessary for efficient processing of inverted faces. LAY SUMMARY: We found alterations in the neurophysiological responses to inverted faces in children with ASD, that were not reflected in the evoked responses, and were not observed in the responses to upright faces. These alterations included reduced local functional connectivity in the fusiform face area (FFA), and decreased long-range alpha-band modulated functional connectivity between the FFA and the left IFG. The magnitude of long-range functional connectivity between the FFA and the inferior frontal gyrus was correlated with the severity of ASD.

A new hypertonic saline assay for analgesic screening in mice: effects of animal strain, sex, and diurnal phase.

There exists a pressing need for the identification of novel analgesics. We recently reported on a new preclinical assay for rapid analgesic screening based on intraplantar (i.pl.) injection of 10% hypertonic saline (HS) in female outbred (CD-1) mice. Herein, we characterized the HS assay's performance in inbred (C57BL/6) mice, sensitivity to sex differences, and effects of diurnal rhythm phase. In randomized, controlled, blinded in vivo animal experiments, we studied nociceptive responses induced by i.pl. HS in C57BL/6 (vs CD-1) mice of both sexes (n=240) and determined diurnal rhythm phase effects in female animals. We established the HS assay's sensitivity to morphine by constructing dose-response curves and calculating half-maximal inhibitory doses (ID50s). The injection of i.pl. HS produced nociceptive (licking and biting) responses in all C57BL/6 mice tested. In both C57BL/6 and CD-1 mice, the mean (95% confidence interval [CI]) response magnitudes were greater in females vs males (C57BL/6: 87 sec [64 to 110] vs 45 sec [29 to 61]; difference in means, 42 sec; 95% CI, 17 to 68; P < 0.001; n = 10/group; CD-1: 110 sec [95 to 126] vs 53 sec [32 to 74]; difference in means, 57 sec; 95% CI, 34 to 79; P < 0.001; n = 10/group). The mean (95% CI) nociceptive responses were greater at 24:00 hr than at 12:00 hr in C57BL/6 mice (64 sec [40 to 88] vs 37 sec [24 to 51]; difference in means, 27 sec; 95% CI, 7 to 47; P = 0.007; n = 10/group), but not in CD-1 mice (P = 0.97). Intravenous morphine dose-dependently attenuated nociceptive responses of both C57BL/6 and CD-1 mice (ID50, 0.6 and 2.5 mg·kg-1, respectively; P = 0.41). These findings in inbred and outbred mice solidify the utility of the HS assay as an effective, rapid, robust, and versatile preclinical tool for analgesic screening.

High-throughput measurement of fibroblast rhythms reveals genetic heritability of circadian phenotypes in diversity outbred mice and their founder strains

Circadian variability is driven by genetics and Diversity Outbred (DO) mice is a powerful tool for examining the genetics of complex traits because their high genetic and phenotypic diversity compared to conventional mouse crosses. The DO population combines the genetic diversity of eight founder strains including five common inbred and three wild-derived strains. In DO mice and their founders, we established a high-throughput system to measure cellular rhythms using in vitro preparations of skin fibroblasts. Among the founders, we observed strong heritability for rhythm period, robustness, phase and amplitude. We also found significant sex and strain differences for these rhythms. Extreme differences in period for molecular and behavioral rhythms were found between the inbred A/J strain and the wild-derived CAST/EiJ strain, where A/J had the longest period and CAST/EiJ had the shortest. In addition, we measured cellular rhythms in 329 DO mice, which displayed far greater phenotypic variability than the founders—80% of founders compared to only 25% of DO mice had periods of ~ 24 h. Collectively, our findings demonstrate that genetic diversity contributes to phenotypic variability in circadian rhythms, and high-throughput characterization of fibroblast rhythms in DO mice is a tractable system for examining the genetics of circadian traits.

What you need to know to avoid constipation

Introduction. Constipation is one of the most common human diseases. Doctors in England consider constipation a “secret national problem” because 50% of the population takes laxatives.The aim of this work was the introduction of chronomedicine approach to the problem of constipation.Method the study was chronoenterographia – week monitoring of the circadian rhythm of defecation.Materials. More than 2,500 people aged 24–75 years, 66% of women, were examined. The frequency and acrophase of the defecation rhythm and quality of life were analyzed.Results: circadian regular defecation rhythm (Euenteria – 7 times/wk) and irregular (Bradyenteria – 1–6 times/week) was isolated. It is shown that the presence of the morning phase of the defecation rhythm contributes to its regularity, and the absence of this phase increases the risk of constipation by 4 times. The earlier defecation occurs – the less often constipation occurs. Euenteria associated with a high level of quality of life, but Bradyenteria – on the contrary. According to the frequency of defecation, there are 3 stages of Bradyenteria: light (5–6 times/week), moderate (3–4 times/week), severe (1–2 times/week, constipation). The Roman-IV criteria for constipation recommend diagnosing only the severe stage of Bradyenteria (less than 3 times/week), and the first 2 stages of it are not diagnosed.Conclusion. Late diagnosis of constipation leads to complications: hemorrhoids, diverticulitis and colorectal cancer. For the regularity of defecation, the contribution of timely stool phase is commensurate with the complex of adequate nutrition, sufficient physical activity and optimal sleep. In order not to suffer from constipation, you need to know about regularity, timeliness and complexity. In outpatient surgery, polyethylene glycol, psyllium and sodium picosulfate are most often used to restore the regular rhythm of defecation.

Effects of prolonged night-time light exposure and traffic noise on the behavior and body temperature rhythmicity of the wild desert rodent, Gerbillus tarabuli

ABSTRACT The aim of this study was to demonstrate for the first time in Tarabul’s gerbils (Gerbillus tarabuli), the effects of simultaneous exposure to two major environmental stressors – light and noise pollutions – on the body temperature rhythm and anxious behavior. Seven groups, each consisting of 6 adult male gerbils, were subjected to a standard LD cycle (12 L:12D) with lights on at 08:00 h and off at 20:00 h, constant conditions (total darkness, DD), prolonged nighttime exposure to light (PEL: 18 L:6D) with lights on at 08:00 h and off at 02:00 h, mimicking prolonged exposure to light pollution in peri-urban areas, exposure to auditory stress (TNS) of 80 dB, and conditions combining PEL&TNS. The body temperature circadian rhythm was recorded, and behavioral tests were performed at the end of experimental phases. The results revealed the existence, for the first time in Gerbilus tarabuli, of an endogenous circadian rhythm of body temperature with a period of 23.8 ± 0.04 h. Prolonged exposure to light at night (PEL) induced a significant phase delay (02 h 09 min ± 0.16 h) of the rhythm, with an acrophase (peak time) occurring at 04:42 ± 0.13 h instead of 02:33 ± 0.21 h. Exposure to TNS for 4 hours per night induced a significant increase of the amplitude of the rhythm and a decrease of the rhythm regularity (robustness of 73.26% in TNS vs. 82.32 in control condition). While combining TNS and PEL significantly delayed the phase of the Tb rhythm by 3 h 10 min (acrophase at 06:39 ± 0.37 h instead of 02:33 ± 0.21 h), increased the amplitude, and significantly reduced the stability of the rhythm (robustness of 67.25% in PEL&TNS vs. 82.32 in control condition). PEL&TNS and TNS environments induce an important stress in gerbils highlighted by a significant decrease of the number of line crossings and time spent in the center area of the open field test. Furthermore, elevated plus maze test revealed gerbils of the PEL&TNS and TNS conditions significantly visited the lowest number of open arms and spent a shorter amount of time in it. In addition, these conditions were responsible for less activity (total number of entries in arms) than in the control and PEL conditions. These results indicate clearly that in the desert area, peri-urban light and noise pollutions disturb the circadian rhythm components and alter the behavior of Tarabul’s gerbils inducing an anxious state.

Chapter 24 - Chronotherapy

The objective of chronotherapy is to optimize medical treatments taking into account the body's circadian rhythms. Chronotherapy is referred to and practiced in two different ways: (1) to alter the sleep-wake rhythms of patients to improve the sequels of several pathologies; (2) to take into account the circadian rhythms of patients to improve therapeutics. Even minor dysfunction of the biological clock can greatly affect sleep/wake physiology causing excessive diurnal somnolence, increase in sleep onset latency, phase delays or advances in sleep onset, frequent night awakenings, reduced sleep efficiency, delayed and shortened rapid eye movement sleep, or increased periodic leg movements. Chronotherapy aims to restore the proper circadian pattern of the sleep-wake cycle, through adequate sleep hygiene, timed light exposure, and the use of chronobiotic medications, such as melatonin, that affect the output phase of circadian rhythms, thus controlling the clock. Concerning the second use of chronotherapy, therapeutic outcomes as diverse as the survival after open-heart surgery or the efficacy and tolerance to chemotherapy vary according to the time of day. However, humans are heterogeneous concerning the timing of their internal clocks. Not only different chronotypes exist but also the endogenous human circadian period (τ) is not a stable trait as it depends on many internal and external factors. If any scheduled therapeutic intervention is going to be optimized, a tool is needed for simple diagnostic and objectively measurement of an individual's internal time at any given time. Methodologic advances like the use of single-sample gene expression and metabolomics are discussed.

Phasic modulation of hippocampal synaptic plasticity by theta rhythm.

Theta rhythm and long-term potentiation (LTP) are 2 remarkable discoveries. The theta rhythm is an oscillatory neural activity of 3-10 Hz in the hippocampus. LTP is implicated as a cellular basis of memory, but the function of theta oscillation in memory is not clear. This review suggests that theta rhythm bestows optimal conditions for hippocampal LTP and memory encoding. Theta rhythm in hippocampal CA1 is generated mainly by 2 oscillating dipoles-somatic-inhibition and phase-shifted, distal dendritic excitation, with a smaller contribution by rhythmic proximal (CA3) excitation and distal inhibition. Our recent study showed that LTP of the excitatory synapses on the basal or apical dendrites of CA1 pyramidal cells peaked twice in a theta cycle, at the rising (R) and the midcycle (M) phase of the theta rhythm recorded at the distal apical dendrites. In contrast, evoked population spike excitability peaked at a single phase near the midcycle. We infer that R and M peaks of LTP correspond to maximal dendritic depolarization and maximal somatic depolarization of CA1 pyramidal cells, respectively. A ∼50° phase shift between LTP-versus-theta-phase functions suggests independent LTP at the basal and apical dendrites. It is argued that theta phase-dependent LTP occurs under physiological conditions, by pairing presynaptic activity with oscillating postsynaptic depolarization. Place cells, showing intrinsic membrane potential oscillations, are ideal LTP participants. It is suggested that theta phase-dependent LTP contributes to memory encoding, and disruption of either theta oscillation or LTP may disrupt memory in various neurological disorders, including epilepsy and Alzheimer's disease. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Absent phasing of respiratory and locomotor rhythms in running mice.

Examining whether and how the rhythms of limb and breathing movements interact is highly informative about the mechanistic origin of hyperpnoea during running exercise. However, studies have failed to reveal regularities. In particular, whether breathing frequency is inherently proportional to limb velocity and imposed by a synchronization of breaths to strides is still unclear. Here, we examined respiratory changes during running in the resourceful mouse model. We show that, for a wide range of trotting speeds on a treadmill, respiratory rate increases to a fixed and stable value irrespective of trotting velocities. Respiratory rate was yet further increased during escape-like running and most particularly at gallop. However, we found no temporal coordination of breaths to strides at any speed, intensity, or gait. Our work thus highlights that exercise hyperpnoea can operate, at least in mice and in the presently examined running regimes, without phasic constraints from limb movements.