Rhythmic Activity Research Articles

Representations of imaginary scenes and their properties in cortical alpha activity

Imagining natural scenes enables us to engage with a myriad of simulated environments. How do our brains generate such complex mental images? Recent research suggests that cortical alpha activity carries information about individual objects during visual imagery. However, it remains unclear if more complex imagined contents such as natural scenes are similarly represented in alpha activity. Here, we answer this question by decoding the contents of imagined scenes from rhythmic cortical activity patterns. In an EEG experiment, participants imagined natural scenes based on detailed written descriptions, which conveyed four complementary scene properties: openness, naturalness, clutter level and brightness. By conducting classification analyses on EEG power patterns across neural frequencies, we were able to decode both individual imagined scenes as well as their properties from the alpha band, showing that also the contents of complex visual images are represented in alpha rhythms. A cross-classification analysis between alpha power patterns during the imagery task and during a perception task, in which participants were presented images of the described scenes, showed that scene representations in the alpha band are partly shared between imagery and late stages of perception. This suggests that alpha activity mediates the top-down re-activation of scene-related visual contents during imagery.

Circadian-independent light regulation of mammalian metabolism.

The daily light-dark cycle is a key zeitgeber (time cue) for entraining an organism's biological clock, whereby light sensing by retinal photoreceptors, particularly intrinsically photosensitive retinal ganglion cells, stimulates the suprachiasmatic nucleus of the hypothalamus, a central pacemaker that in turn orchestrates the rhythm of peripheral metabolic activities. Non-rhythmic effects of light on metabolism have also been long known, and their transduction mechanisms are only beginning to unfold. Here, we summarize emerging evidence that, in mammals, light exposure or deprivation profoundly affects glucose homeostasis, thermogenesis and other metabolic activities in a clock-independent manner. Such light regulation could involve melanopsin-based, intrinsically photosensitive retinal ganglion cell-initiated brain circuits via the suprachiasmatic nucleus of the hypothalamus and other nuclei, or direct stimulation of opsins expressed in the hypothalamus, adipose tissue, blood vessels and skin to regulate sympathetic tone, lipolysis, glucose uptake, mitochondrial activation, thermogenesis, food intake, blood pressure and melanogenesis. These photic signalling events may coordinate with circadian-based mechanisms to maintain metabolic homeostasis, with dysregulation of this system underlying metabolic diseases caused by aberrant light exposure, such as environmental night light and shift work.

Invertebrate sounds from photic to mesophotic coral reefs reveal vertical stratification and diel diversity.

Although mesophotic coral ecosystems account for approximately 80% of coral reefs, they remain largely unexplored due to their challenging accessibility. The acoustic richness within reefs has led scientists to consider passive acoustic monitoring as a reliable method for studying both altiphotic and mesophotic coral reefs. We investigated the relationship between benthic invertebrate sounds (1.5-22.5kHz), depth, and benthic cover composition, key ecological factors that determine differences between altiphotic and mesophotic reefs. Diel patterns of snaps and peak frequencies were also explored at different depths to assess variations in biorhythms. Acoustic recorders were deployed at 20m, 60m, and 120m depths across six islands in French Polynesia. The results indicated that depth is the primary driver of differences in broadband transient sound (BTS) soundscapes, with sound intensity decreasing as depth increases. At 20-60m, sounds were louder at night. At 120m depth, benthic activity rhythms exhibited low or highly variable levels of diel variation, likely a consequence of reduced solar irradiation. On three islands, a peculiar peak in the number of BTS was observed every day between 7 and 9 PM at 120m, suggesting the presence of cyclic activities of a specific species. Our results support the existence of different invertebrate communities or distinct behaviors, particularly in deep mesophotic reefs. Overall, this study adds to the growing evidence supporting the use of passive acoustic monitoring to describe and understand ecological patterns in mesophotic reefs.

Light pollution affects activity differentially across breeding stages in an urban exploiter: an experiment in the house sparrow (Passer domesticus)

Artificial Light At Night (ALAN) is a major urban perturbation, which can have detrimental effects on wildlife. Recent urban planning has led to an increased use of white light emission diodes (LEDs) in cities. However, little is known about the effects of this type of ALAN on wild vertebrates, especially during reproduction. We designed an experiment to test the impact of ALAN on the activity rhythms (daily time of first activity (TFA) and time of last activity (TLA)) of captive House sparrows (Passer domesticus) during several reproductive stages (from pre-breeding to post-breeding). We also tested the impact of ALAN on reproductive performance (laying date, clutch size, hatching and fledging success). Experimental birds were active earlier in the morning (earlier TFA) relative to controls although experimental and control birds did not differ in their TLA. The effect of ALAN on TFA was apparent during specific stages only (pre-breeding and chick-rearing stages), suggesting that sparrows actively adjust their activity in response to ALAN only during specific periods. This impact of ALAN on activity did not persist through the whole breeding season, suggesting that sparrows may habituate to ALAN. Alternatively, they may not be able to sustain a long-term increased activity in response to ALAN because of sleep deprivation and related physiological costs. Finally, we did not find any impact of ALAN on the reproductive performance of captive house sparrows held under optimal conditions. This suggests that ALAN may not be dramatically detrimental to the reproduction of this urban exploiter, at least when food availability is not constraining.

High-energy pacing inhibits slow-wave dysrhythmias in the small intestine.

The motility of the gastrointestinal tract is coordinated in part by rhythmic slow waves, and disrupted slow-wave patterns are linked to functional motility disorders. At present, there are no treatment strategies that primarily target slow-wave activity. This study assessed the use of pacing to suppress glucagon-induced slow-wave dysrhythmias in the small intestine. Slow waves in the jejunum were mapped in vivo using a high-resolution surface-contact electrode array in pigs (n = 7). Glucagon was intravenously administered to induce hyperglycemia. Slow-wave propagation patterns were categorized into antegrade, retrograde, collision, pacemaker, and uncoupled activity. Slow-wave characteristics such as period, amplitude, and speed were also quantified. Postglucagon infusion, pacing was applied at 4 mA and 8 mA and the resulting slow waves were quantified spatiotemporally. Antegrade propagation was dominant throughout all stages with a prevalence of 55 ± 38% at baseline. However, glucagon infusion resulted in a substantial and significant increase in uncoupled slow waves from 10 ± 8% to 30 ± 12% (P = 0.004) without significantly altering the prevalence of other slow-wave patterns. Slow-wave frequency, amplitude, and speed remained unchanged. Pacing, particularly at 8 mA, significantly suppressed dysrhythmic slow-wave patterns and achieved more effective spatial entrainment (85%) compared with 4 mA (46%, P = 0.039). This study defined the effect of glucagon on jejunal slow waves and identified uncoupling as a key dysrhythmia signature. Pacing effectively entrained rhythmic activity and suppressed dysrhythmias, highlighting the potential of pacing for gastrointestinal disorders associated with slow-wave abnormalities.NEW & NOTEWORTHY Glucagon was infused in pigs to induce hyperglycemia and the resulting slow-wave response in the intact jejunum was defined in high resolution for the first time. Subsequently, with pacing, the glucagon-induced dysrhythmias were suppressed and spatially entrained for the first time with a success rate of 85%. The ability to suppress slow-wave dysrhythmias through pacing is promising in treating motility disorders that are associated with intestinal dysrhythmias.

Speaker Competence Affects Prefrontal Theta and Occipital Alpha Power during Selective Word Learning in Preschoolers.

In the present study, we investigated the cognitive processes underlying selective word learning in preschoolers. We measured rhythmic neural activity in the theta (4-8 Hz) and alpha frequency range (7-12 Hz) in 67 four-year-olds. EEG was recorded during anticipation and encoding of novel labeling events performed by a speaker who had previously shown either competence (correct) or incompetence (incorrect) in labeling familiar objects. In both groups, children selected the target object equally often upon recall. However, children observing the incompetent speaker revealed weaker representations of novel words indicated by an increased likelihood for selecting familiar but incorrect items upon recall. Modulations in theta and alpha power suggest differential processing of novel label-object pairs depending on the speakers' competence. In the incompetent, but not the competent, speaker condition, increases in prefrontal theta power during anticipation and encoding were related to increased recall success. Findings suggest that theta power in the present study reflects cognitive control. In both conditions, occipital alpha power-indicating attentional processes-reflected familiarity with novel items, but in opposite directions. In familiar item trials, alpha power was increased observing the incompetent and decreased observing the competent speaker. Thus, both cognitive control and attention processes during word learning are differentially affected by speaker characteristics.

Effects of the low Fowler's sleep position and methazolamide treatment on sleep bruxism: A randomized controlled trial.

Intracranial pressure is one of the determinants of sympathetic activities, and sleep bruxism is associated with increased sympathetic activities. This study aimed to investigate effects of the low Fowler's sleep position and methazolamide treatment on the occurrence of rhythmic masticatory muscle activities/sleep bruxism episodes in patients with sleep bruxism in a randomized controlled trial. Polysomnographic recordings were performed on the patients with sleep bruxism sleeping in the low Fowler's (15°-30°) or supine position (n = 11), and with methazolamide or placebo treatment (100 mg, 3-4 hr before bedtime, P.O., n = 9), and changes in sleep variables and heart rate variance during sleep in the low Fowler's position or with methazolamide treatment were determined. Sleep bruxism index, number of masseter muscle electromyographic bursts per hour of sleep, ratio of rhythmic masticatory muscle activities/sleep bruxism duration to the total sleep duration, index of total limb movements, index of limb movements with rhythmic masticatory muscle activities, and number of sleep bruxism clusters per hour of sleep in the low Fowler's position and after methazolamide intake were significantly smaller (p < 0.05-0.001) than those in the supine position and after placebo intake, respectively. The low-frequency heart rate variance powers during non-rapid eye movement sleep stage 2 (N2) in the low Fowler's position and with methazolamide treatment were significantly lower (p < 0.05) than those during sleep in the supine position and with placebo treatment, respectively. In conclusion, sleep in the low Fowler's position and methazolamide treatment were associated with significant decreases in the occurrence of rhythmic masticatory muscle activities/sleep bruxism episodes, which might be due to a reduction in intracranial pressure and sympathetic activities mainly during non-rapid eye movement sleep stage 2.

Association Between QRS Characteristics in Pulseless Electrical Activity and Survival Outcome in Cardiac Arrest Patients: A Systematic Review and Meta-Analysis

Objective Recent studies have shown inconsistent results regarding the association between QRS characteristics and survival outcomes in patients with cardiac arrest and pulseless electrical activity (PEA) rhythms. This meta-analysis aimed to identify the usefulness of QRS width and frequency as prognostic tools for outcomes in patients with cardiac arrest and PEA rhythm. Methods Extensive searches were conducted using Medline, Embase, and the Cochrane Library to find articles published from database inception to 4 June 2023. Studies that assessed the association between the QRS characteristics of cardiac arrest patients with PEA rhythm and survival outcomes were included. The Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies. Results A total of 9727 patients from seven observational studies were included in this systematic review and meta-analysis. The wide QRS group (QRS ≥ 120 ms) was associated with significantly higher odds of mortality than the narrow QRS group (QRS < 120 ms) (odds ratio (OR) = 1.86, 95% confidence interval (CI) = 1.11–3.11, I 2 = 58%). The pooled OR for mortality was significantly higher in patients with a QRS frequency of < 60/min than in those with a QRS frequency of ≥ 60/min (OR = 1.90, 95% CI = 1.19–3.02, I 2 = 65%). Conclusions Wide QRS width or low QRS frequency is associated with increased odds of mortality in patients with PEA cardiac arrest. These findings may be beneficial to guide the disposition of cardiac arrest patients with PEA during resuscitation.

Circadian rhythm in pro-arrhythmic activity of pulmonary vein cardiomyocytes

Abstract Introduction Cardiomyocytes in the pulmonary vein (PV) sleeves are a major source of ectopic activity driving atrial fibrillation (AF) and episodes of AF in patients are more prevalent at night. While it is known that circadian clocks within the heart regionally control 24-hour variation in pacemaking and ventricular repolarisation, the mechanisms underlying the nighttime preponderance in AF are unknown. Purpose This study addresses the hypothesis that circadian rhythms exist in the pro-arrhythmic activity of PV cardiomyocytes. Methods Male Wistar rats maintained in a 24-hour cycle of 12-hr light/dark (lights-on at Zeitgeber time, ZT=0; lights-off, ZT12) were subject to terminal general anaesthesia (140 mg/kg Na pentobarbital i.p.) at ZT=0, 6, 12 or 18 hr and the hearts removed. RNA was extracted from left atrial (LA) appendage (LAA) and proximal PV at the LA/PV junction (3 rats per ZT) and RNA sequencing conducted. Reads were mapped to the rat genome, counts normalised and models in which ZT was or was not included as a factor compared (Likelihood Ratio Test, adjusted-P&amp;lt;0.01). Whole-cell current clamp recordings were made from cardiomyocytes isolated from the proximal PV (n=308) and the LAA (n=264) (N=74 rats). The effects of noradrenaline (NA, 1 µM) and acetylcholine (ACh, 1 µM) were examined. Data were plotted against the ZT of the time of recording and fitted to a sine wave to establish circadian rhythmicity (P&amp;lt;0.05, extra-sum-of-squares F-test). The effect of ≥24 hr constant dark in the period immediately before experiment was examined. Data are reported as mean ± standard error. Results The expression of 1368 genes varied significantly with ZT, including circadian clock components (e.g. Bmal1, Per1). PV cells were larger than LAA cells (73±1.6 pF vs 53±1.3 pF, P&amp;lt;0.0001) and had more depolarised resting membrane potential (-69±0.2 mV vs -72±0.1 mV, P&amp;lt;0.0001). Both cell types showed circadian variation in action potential duration at 90% repolarisation (APD90) and frequency of pro-arrhythmic activity. Pro-arrhythmic activity was greatest in PV cells and the frequency was greater during the rest phase (ZT0-12) in both cell types. In contrast, the circadian rhythm in APD90 differed between cell type, with the longest APD­­90 recorded during the active phase in PV cells (ZT12-24) but during the rest phase in LAA cells. Pro-arrhythmic activity was increased by NA and decreased by ACh in both cell types with maximal effect during the rest phase. Conclusion Circadian variation in APD90 and proarrhythmic-activity has been demonstrated in isolated proximal PV and LAA cardiomyocytes, with differences in rhythm between the two cell types. RNA sequencing suggests the presence of peripheral clocks in LAA and PV cardiomyocytes. Understanding these mechanisms is important in development of future therapeutic options for AF.

Psychomotor symptoms, cognitive impairments and suicidal thoughts after COVID-19 infection: a case report and the possible allostatic mechanism.

Although neuropsychiatric manifestations are common in survivors of coronavirus disease 2019 (COVID-19), the pathophysiology is not yet elucidated. Here we describe the case of a geriatric inpatient who developed postCOVID depression with psychomotor retardation, anxiety, hopelessness, executive function problems, and suicidal ideations. The language problems and cognitive impairments coemerged with the motor problems. We propose a mechanism associated with problems in energy prediction and regulation in which the coronavirus infection, which causes neuroinflammation and viral activity in the nervous system, interferes with the reward pathway and sensory prediction process. Sigma-1 receptor agonists such as sertraline may regulate energy expenditure and, thus, be beneficial to the process. The treatment improvements in our patient included those in the autonomic nervous system, activity, and circadian rhythm.

Исследование соотношений между показателями ритмической активности сердца человека

The purpose of this article was to determine the correlations between the electrical and mechanical parameters of the rhythmic activity of the heart (HRA) in humans taking into account age and the effect of functional loads. Materials and methods. The research involved 146 people of both sexes aged between two hours after birth and 92 years, who were examined using functional tests that differed depending on the age of the subjects. Electrocardiogram (ECG) and heart rate (HR) parameters were recorded in the standard lead II using the Poly-Spectrum ECG system (Neurosoft, Ivanovo). Results. Correlations between HRA parameters can be traced from the first hours of post-embryogenesis throughout the rest of a person’s life. The data obtained indicate a dependence of HRA on the age and on the effect of functional tests, as well as confirm the proposition that there is an inverse relationship between HR dynamics and the dynamics of myocardial electrical parameters. ECG recordings at birth indicate that the correlations between ECG and HR are formed as early as in the prenatal period. Their correlations in people aged between 70 and 92 years indicate a strain associated with the wear and tear of the body’s functional systems. HR and ECG parameters are based on the electrical properties of the myocardium, which are significantly affected by the autonomic nervous system (ANS). A linear range of correlations between HR and ECG intervals was compiled. The maximum values of the duration of the PP interval and TP segment correspond to the minimum HR values. With an increase in HR from 40 to 80 beats/min, the duration of the TP segment decreases twoto three-fold. With HR reaching 120 ± 5 beats/min, the duration of the TP segment drops to zero. Since the increase in HR continues further in response to functional tests, it is obvious that at this stage the process is provided only by the neurohumoral components of the ANS. Due to the maximum variability of the duration of the TP segment, its most important role in the organization of HRA is emphasized.

Effects of transcranial direct current stimulation on brain activity and cortical functional connectivity in children with autism spectrum disorders.

Transcranial direct current stimulation (tDCS) has emerged as a therapeutic option to mitigate symptoms in individuals with autism spectrum disorder (ASD). Our study investigated the effects of a two-week regimen of tDCS targeting the left dorsolateral prefrontal cortex (DLPFC) in children with ASD, examining changes in rhythmic brain activity and alterations in functional connectivity within key neural networks: the default mode network (DMN), sensorimotor network (SMN), and dorsal attention network (DAN). We enrolled twenty-six children with ASD and assigned them randomly to either an active stimulation group (n=13) or a sham stimulation group (n=13). The active group received tDCS at an intensity of 1mA to the left DLPFC for a combined duration of 10 days. Differences in electrical brain activity were pinpointed using standardized low-resolution brain electromagnetic tomography (sLORETA), while functional connectivity was assessed via lagged phase synchronization. Compared to the typically developing children, children with ASD exhibited lower current source density across all frequency bands. Post-treatment, the active stimulation group demonstrated a significant increase in both current source density and resting state network connectivity. Such changes were not observed in the sham stimulation group. tDCS targeting the DLPFC may bolster brain functional connectivity in patients with ASD, offering a substantive groundwork for potential clinical applications.

E3 ubiquitin ligase UBR5 modulates circadian rhythm by facilitating the ubiquitination and degradation of the key clock transcription factor BMAL1.

The circadian clock is the inner rhythm of life activities and is controlled by a self-sustained and endogenous molecular clock, which maintains a ~ 24 h internal oscillation. As the core element of the circadian clock, BMAL1 is susceptible to degradation through the ubiquitin-proteasome system (UPS). Nevertheless, scant information is available regarding the UPS enzymes that intricately modulate both the stability and transcriptional activity of BMAL1, affecting the cellular circadian rhythm. In this work, we identify and validate UBR5 as a new E3 ubiquitin ligase that interacts with BMAL1 by using affinity purification, mass spectrometry, and biochemical experiments. UBR5 overexpression induced BMAL1 ubiquitination, leading to diminished stability and reduced protein level of BMAL1, thereby attenuating its transcriptional activity. Consistent with this, UBR5 knockdown increases the BMAL1 protein. Domain mapping discloses that the C-terminus of BMAL1 interacts with the N-terminal domains of UBR5. Similarly, cell-line-based experiments discover that HYD, the UBR5 homolog in Drosophila, could interact with and downregulate CYCLE, the BMAL1 homolog in Drosophila. PER2-luciferase bioluminescence real-time reporting assay in a mammalian cell line and behavioral experiments in Drosophila reveal that UBR5 or hyd knockdown significantly reduces the period of the circadian clock. Therefore, our work discovers a new ubiquitin ligase UBR5 that regulates BMAL1 stability and circadian rhythm and elucidates the underlying molecular mechanism. This work provides an additional layer of complexity to the regulatory network of the circadian clock at the post-translational modification level, offering potential insights into the modulation of the dysregulated circadian rhythm.

Correlation Analysis of Multi-Scale Ictal EEG Signals in Juvenile Myoclonic Epilepsy.

To explore the time-frequency structure and cross-scale coupling of electroencephalography (EEG) signals during seizure in juvenile myoclonic epilepsy (JME), correlations between different leads, as well as dynamic evolution in epileptic discharge, progression and end of seizure were examined. EEG data were obtained for 10 subjects with JME and 10 normal controls and were decomposed using gauss continuous wavelet transform (CWT). The phase amplitude coupling (PAC) relationship between the 11th (4.57 Hz) and 17th (0.4 Hz) scale was investigated. Correlations were examined between the 11th and 17th scale EEG signals in different leads during seizure, using multi-scale cross correlation analysis. The time-frequency structure of JME subjects showed strong rhythmic activity in the 11th and 17th scales and a close PAC was identified. Correlation analysis revealed that the ictal JME correlation first increased in the anterior head early in seizure and gradually expanded to the posterior head. PAC was exhibited between the 11th and 17th scales during JME seizure. The results revealed that the correlation in the anterior leads was higher than the posterior leads. In the perictal period, the 17th scale EEG signal preceded the 11th scale signal and remained for some time after a seizure. This suggests that the 17th scale signal may play an important role in JME seizure.

Increasing Rhythmic Gymnastics Skills in Students Through M-Gym Media

The purpose of this study was to determine whether M-Gym media could help students improve their rhythmic gymnastics skills. This study was based on Borg and Gall's research. This study was planned at Universitas Negeri Medan's Faculty of Sports Science. Meanwhile, this study was carried out for one semester, from April 2nd to April 29th, 2024. The findings of this study revealed that in the small class trial, 70% of the students' rhythmic activity abilities were evaluated as weak during the pretest stage. The test was performed on students before they begin learning with m-gym media. However, when students in small classes were taught with m-gym media, their results were different. The majority of students (83.3%) have good rhythmic abilities. In the large class trial, the majority of students' rhythmic activity abilities were rated as inadequate at the pretest stage, 56%. The test was performed on students before they begin learning with M-Gym media. However, when students in big classes were taught utilizing M-Gym media, the results were different. Most students are proficient in rhythmic gymnastics. The conclusion showed that students could perform fundamental rhythmic activity motions correctly when provided directions during learning utilizing M-Gym media.

Temporal niche partitioning among sympatric wild and domestic ungulates between warm and cold seasons

The coexistence of sympatric species with similar ecological niches has been a central issue in ecology. Clarifying the daily activity patterns of sympatric wild ungulates can help understand their temporal niche differentiation and the mechanisms of coexistence, providing information for their conservation. The Baotianman National Nature Reserve in northern China is rich in wild ungulates, but little is known about the daily activity patterns of wild ungulates in the area, making it difficult to develop effective conservation strategies. We studied five representative wild ungulates (i.e. forest musk deer, Chinese goral, Reeve’s muntjac, Siberian roe deer, and wild boar) of the region using camera-trapping data, focusing on the seasonal daily activity patterns and effects of seasonal grazing of domestic sheep, to reveal their coexistence based on temporal ecological niche differentiation. Comparative analyses of the seasonal daily activity showed that forest musk deer exhibited a single-peak activity in the warm season. Other ungulates exhibited multipeak activity. All five ungulates differed significantly in daily activity patterns. Notably, wild boar and Reeve’s muntjac showed high overlap coefficients between the cold and warm seasons. In both cold and warm seasons, the five wild ungulates and domestic sheep displayed low overlap in their daily activity rhythms potentially indicating temporal ecological niche differentiation. The results suggest that temporal isolation might be a strategy for wild ungulates to avoid domestic sheep and reduce interspecific competition, and that temporal ecological niche differentiation potentially promoted the coexistence among the studied sympatric ungulates. This understanding may provide new insights for the development of targeted conservation strategies.

Error Function Optimization to Compare Neural Activity and Train Blended Rhythmic Networks.

We present a novel set of quantitative measures for "likeness" (error function) designed to alleviate the time-consuming and subjective nature of manually comparing biological recordings from electrophysiological experiments with the outcomes of their mathematical models. Our innovative "blended" system approach offers an objective, high-throughput, and computationally efficient method for comparing biological and mathematical models. This approach involves using voltage recordings of biological neurons to drive and train mathematical models, facilitating the derivation of the error function for further parameter optimization. Our calibration process incorporates measurements such as action potential (AP) frequency, voltage moving average, voltage envelopes, and the probability of post-synaptic channels. To assess the effectiveness of our method, we utilized the sea slug Melibe leonina swim central pattern generator (CPG) as our model circuit and conducted electrophysiological experiments with TTX to isolate CPG interneurons. During the comparison of biological recordings and mathematically simulated neurons, we performed a grid search of inhibitory and excitatory synapse conductance. Our findings indicate that a weighted sum of simple functions is essential for comprehensively capturing a neuron's rhythmic activity. Overall, our study suggests that our blended system approach holds promise for enabling objective and high-throughput comparisons between biological and mathematical models, offering significant potential for advancing research in neural circuitry and related fields.

Association of Rest-Activity Rhythm and Risk of Developing Dementia or Mild Cognitive Impairment in the Middle-Aged and Older Population: Prospective Cohort Study.

The relationship between 24-hour rest-activity rhythms (RARs) and risk for dementia or mild cognitive impairment (MCI) remains an area of growing interest. Previous studies were often limited by small sample sizes, short follow-ups, and older participants. More studies are required to fully explore the link between disrupted RARs and dementia or MCI in middle-aged and older adults. We leveraged the UK Biobank data to examine how RAR disturbances correlate with the risk of developing dementia and MCI in middle-aged and older adults. We analyzed the data of 91,517 UK Biobank participants aged between 43 and 79 years. Wrist actigraphy recordings were used to derive nonparametric RAR metrics, including the activity level of the most active 10-hour period (M10) and its midpoint, the activity level of the least active 5-hour period (L5) and its midpoint, relative amplitude (RA) of the 24-hour cycle [RA=(M10-L5)/(M10+L5)], interdaily stability, and intradaily variability, as well as the amplitude and acrophase of 24-hour rhythms (cosinor analysis). We used Cox proportional hazards models to examine the associations between baseline RAR and subsequent incidence of dementia or MCI, adjusting for demographic characteristics, comorbidities, lifestyle factors, shiftwork status, and genetic risk for Alzheimer's disease. During the follow-up of up to 7.5 years, 555 participants developed MCI or dementia. The dementia or MCI risk increased for those with lower M10 activity (hazard ratio [HR] 1.28, 95% CI 1.14-1.44, per 1-SD decrease), higher L5 activity (HR 1.15, 95% CI 1.10-1.21, per 1-SD increase), lower RA (HR 1.23, 95% CI 1.16-1.29, per 1-SD decrease), lower amplitude (HR 1.32, 95% CI 1.17-1.49, per 1-SD decrease), and higher intradaily variability (HR 1.14, 95% CI 1.05-1.24, per 1-SD increase) as well as advanced L5 midpoint (HR 0.92, 95% CI 0.85-0.99, per 1-SD advance). These associations were similar in people aged <70 and >70 years, and in non-shift workers, and they were independent of genetic and cardiovascular risk factors. No significant associations were observed for M10 midpoint, interdaily stability, or acrophase. Based on findings from a large sample of middle-to-older adults with objective RAR assessment and almost 8-years of follow-up, we suggest that suppressed and fragmented daily activity rhythms precede the onset of dementia or MCI and may serve as risk biomarkers for preclinical dementia in middle-aged and older adults.

Nasal solitary chemosensory cells govern daily rhythm in mouse model of allergic rhinitis

BackgroundWhile the daily rhythm of allergic rhinitis (AR) has long been recognized, the molecular mechanism underlying this phenomenon remains enigmatic. ObjectiveWe aim to investigate the role of circadian clock in AR development and to clarify the mechanism by which the daily rhythm of AR is generated. MethodsAR was induced in mice using the ovalbumin method. Toluidine blue staining, LC-MS/MS analysis, qPCR, and immunoblotting were performed with AR and control mice. ResultsOvalbumin-induced AR is diurnally rhythmic and associated with clock gene disruption in nasal mucosa. In particular, Rev-erbα is generally down-regulated, and its rhythm retained but with a near 12-h phase shift. Furthermore, global knockout of the core clock gene Bmal1 or Rev-erbα increases the susceptibility of mice to AR and blunts AR rhythmicity. Importantly, nasal SCCs (solitary chemosensory cells) are rhythmically activated, and inhibition of the SCC pathway leads to attenuated AR and a loss of its rhythm. Moreover, rhythmic activation of SCCs is accounted for by diurnal expression of ChAT (an enzyme responsible for the synthesis of acetylcholine) and temporal generation of the neurotransmitter acetylcholine. Mechanistically, REV-ERBα trans-represses Chat through direct binding to a specific response element, generating a diurnal oscillation in this target gene. ConclusionThese findings identify SCCs, under the control of REV-ERBα, as a driver of AR rhythmicity, and suggest targeting SCCs as a new avenue for AR management.

Homeostatic regulation of circuit activity through temperature-sensing rather than activity-sensing

Electrical signaling between nerve cells coordinates essential functions of the body. However, neurons face their own regulatory challenges, as they need to produce relatively constant activity patterns as the environment changes. Like homeostatic control that occurs within other organ systems, neural circuits are subject to homeostatic regulation as well, whereby deviations from a set point level of activity elicit corrective responses to maintain circuit output. To achieve this end, neural systems are thought to sense variables that relate to neuronal activity, such as firing rate, ion concentrations, and neuromodulators, to detect when an imbalance in activity occurs. While recording rhythmic motor activity associated with breathing in the American bullfrog, we made the surprising observation that acute cooling to 10°C silenced network activity, but after several minutes, bursting resumed and then overshot baseline frequency upon rewarming. Burst frequency drifted back to the initial value over tens of minutes, consistent with the fast regulation of an activity set point (n=9). Time controls with no temperature changes were stable throughout this period (n=7). Exposing the network to manipulations inducing similar perturbations that silence activity over the same timescale– hypoxia (n=6), glycine (n=6), and tetrodotoxin (n=4)– did not engage feedback regulation. These results suggested that temperature sensing, rather than activity sensing, controls network output. Cation channels activated by cooling in amphibians (TRPM8, n=4; TRPV3, n=4) and L-type Ca2+ channels (n=4) did not contribute to these responses. Experimental activation of the Na+/K+ pump with monensin, which raises intracellular Na+, reduced the compensation response both in the cold (p=0.01, unpaired t-test) and in the overshoot phase following warming, suggesting that cold-dependent inhibition of the Na+/K+ pump enhances network excitability. Finally, NMDA-glutamate receptors played a role in constraining the amount of compensation, as block of NMDARs with D-APV led to compensation that greatly exceeded those observed in the control experiments (n=5, p&lt;0.0001, unpaired t-test), remaining elevated above baseline upon rewarming in all experiments. The cellular mechanisms by which raising intracellular Na+ with monensin and NMDAR signaling influence compensation responses are ongoing. Overall, these results uncover a temperature-sensitive control system that regulates activity in neural circuits. Our results introduce that some neural systems may replace typical activity sensors with regulatory systems that are instead tuned to environmental cues to defend activity set points. R01NS114514, R15NS112920-01A1. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.