Rhythmic Activity Research Articles

Night shift-induced circadian disruption: links to initiation of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and risk of hepatic cancer

The circadian system plays a crucial role in regulating metabolic homeostasis at both systemic and tissue levels by synchronizing the central and peripheral clocks with exogenous time cues, known as zeitgebers (such as the light/dark cycle). Our body’s behavioral rhythms, including sleep-wake cycles and feeding-fasting patterns, align with these extrinsic time cues. The body cannot effectively rest and repair itself when circadian rhythms are frequently disrupted. In many shift workers, the internal rhythms fail to fully synchronize with the end and start times of their shifts. Additionally, exposure to artificial light at night (LAN), irregular eating patterns, and sleep deprivation contribute to circadian disruption and misalignment. Shift work and jet lag disrupt the normal circadian rhythm of liver activity, resulting in a condition known as “circadian disruption”. This disturbance adversely affects the metabolism and homeostasis of the liver, contributing to excessive fat accumulation and abnormal liver function. Additionally, extended working hours, such as prolonged night shifts, may worsen the progression of non-alcoholic fatty liver disease (NAFLD) toward non-alcoholic steatohepatitis (NASH) and increase disease severity. Studies have demonstrated a positive correlation between night shift work (NSW) and elevated liver enzymes, indicative of hepatic metabolic dysfunction, potentially increasing the risk of hepatocellular carcinoma (HCC) related to NAFLD. This review consolidates research findings on circadian disruption caused by NSW, late chronotype, jet lag, and social jet lag, drawing insights from studies involving both humans and animal models that investigate the effects of these factors on circadian rhythms in liver metabolism.

Understanding the clinical management of co-occurring sleep-related bruxism and obstructive sleep apnea in adults: A narrative and critical review.

Sleep-related bruxism (SRB) is a motor oral behavior characterized by tooth grinding and jaw clenching activity, reported by 8%-12% of the adult general population and 3% of older individuals. The frequency of one of its biomarkers, rhythmic masticatory muscle activity (RMMA), remains elevated across ages. Obstructive sleep apnea (OSA) is associated with the brief and repetitive pause of breathing (apnea) and with transient reduction in oxygen (hypoxia). OSA is observed at all ages and in about 50% of older individuals with a male preponderance. SRB clinical assessment is based on self-reporting of tooth grinding sound, awareness of clenching, jaw pain or headache, and clinical observation of tooth damage. OSA clinical assessment is based on sleepiness and fatigue, snoring, sleep quality, and awareness of breathing cessation, plus clinical examination of anatomical factors (e.g., obesity, retrognathia, large tonsil, macroglossia), age, gender, and body mass. Although the literature does not support association or causality between these two conditions, the co-occurrence is reported in about 30%-50% of adults. To confirm a diagnosis of co-occurring SRB and OSA, home sleep testing (HST) may be indicated. A sleep test is performed using electromyography (EMG) of jaw muscle (masseter or temporalis) and cardio-respiratory variables (e.g., air flow, respiratory effort, oxygen level, heart rate). The management of co-occurring SRB and OSA for individuals with prosthodontic needs is challenging to prevent compromising the oro-pharyngeal space and breathing efficiency. OSA treatment in the presence of SRB includes continuous positive airway pressure (CPAP) use alone or with an occlusal splint or mandibular advancement device (MAD). In addition, the following may be considered: supine sleep correction device, myofuncional therapy, medications, and surgeries. All have limitations and risks. Individual variability suggests that phenotyping is mandatory to select the most efficient and personalized treatment.

Disrupted rest-activity circadian rhythms are associated with all-cause mortality in patients with chronic kidney diseases

ABSTRACT Circadian rhythms are important biological contributors to health. Rest activity rhythms (RAR) are emerging as biomarkers of circadian behavior that are associated with chronic disease when abnormal. RAR have not yet been characterized in chronic kidney diseases (CKD). Leveraging the National Health and Nutrition Examination Survey (2011–2014), patients with CKD (n = 1114; Mean [95% CI]: Age, 50 [58–61] y; 52% female) were compared with non-CKD individuals (n = 5885; Age, 47 [46–48] y; 52% female). Actigraphy data were processed for RAR parameters including rhythmic strength (amplitude), the rhythm adjusted mean (mesor), the timing of peak activity (acrophase), activity regularity (inter-daily stability), and activity fragmentation (intra-daily variability). Cox regression was performed to assess RAR parameters for the prediction of all-cause mortality. Compared to non-CKD adults, patients with CKD had a lower rhythmic amplitude and mesor, and exhibited greater fragmentation and less day-to-day stability in RAR (ps < 0.001). Among CKD patients, a lower rhythmic amplitude (HR [95% CI]: 0.88 [0.82–0.96]; p < 0.001), a lower rhythm adjusted mean (0.87 [0.81–0.95]; p = 0.002), and a higher daily activity fragmentation (1.87 [1.10–3.18]; p = 0.023) were associated with an increased risk of all-cause mortality. Patients with CKD showed dampened rhythmic amplitudes and greater fragmentation of activity that were associated with a higher risk of all-cause mortality. These findings demonstrate a relationship between circadian disruption and prognosis in patients with CKD.

The Involvement of GABA in the Modulation of the Rhythm of Electrical Activity in the Small Intestine during Food Deprivation.

In experiments on male Wistar rats, the stages of adaptive changes in the rhythm of periodic electrical activity in the small intestine during food deprivation were identified and the effect of GABA on changes of the rhythm under these conditions was assessed. It was found that on days 1-3 of food deprivation, the migrating myoelectric complex (MMC) in the small intestine is preserved, but the cycle becomes rarer. On days 4-6, MMC disappears, irregular and regular activity with no periods of quiescence is recorded. On days 7-9, predominantly irregular activity of the small intestine with short quiescence periods is observed. Enteral administration of GABA at different stages of food deprivation modulates electrical activity and preserves small intestinal MMC.

Evolution of EEG Findings in Patients with Acute Brain Injury.

Increasing use of continuous EEG monitoring (cEEG) provides the opportunity to observe temporal trends in EEG patterns during the acute phase of brain injury. These trends have not been extensively documented. Methods We conducted a retrospective chart review of patients undergoing cEEG between January 1st and June 30th, 2019, at two academic medical centers. Only patients with acute brain injury having electrographic or electroclinical seizures or epileptic EEG findings on day one of monitoring and ≥ two calendar days of cEEG were included. The temporal evolution of EEG patterns was depicted as a heatmap. Results Of 1356 screened patients, 101 met the study criteria. Clinical acute symptomatic seizures occurred in 30 patients (29.7%) prior to EEG. The median number of days of cEEG was four (IQR 3-6). Amongst patients with electrographic seizures, status epilepticus, generalized periodic discharges, or sporadic epileptiform discharges, 24.6% had improvement and 54.1% had resolution of epileptic EEG findings by the final day of monitoring. In contrast, 65% with lateralized periodic discharges or lateralized rhythmic delta activity persisted or worsened. Overall, 61.4% (62/101) showed either improvement (19.8%) or resolution (41.6%) of their EEG findings prior to hospital discharge. Of the 36 patients with follow-up EEGs at a median of 4.5 (IQR 3-8) months after admission for acute brain injury, 83% (30/36) showed either improvement (1/36; 2.7%) or resolution (29/36; 80.6%). Conclusions We observed a trend towards normalization of most epileptiform patterns except LPDs and LRDA, over time in patients with acute brain injury. The clinical significance of this trend as it relates to antiseizure medication treatment and neurologic outcomes warrants further investigation in an independent cohort.

Cellular mechanisms of synchronized rhythmic burst generation in the ventromedial hypothalamus.

The ventromedial hypothalamus (VMH) plays an important role in feeding behavior and control of the sympathetic nervous system (SNS). The VMH includes a group of neurons that exhibit strong synchronized rhythmic burst firing (so-called VMH oscillation). This VMH oscillation is glucose inhibited, responsive to feeding-related peptides, and is functionally coupled to outputs of the SNS. However, the details of its rhythm generation and synchronization mechanisms are unknown. In the present study, we investigated cellular mechanisms of VMH oscillation by means of electrophysiological recordings and calcium imaging in juvenile rat slice preparations including the VMH. In the electrophysiological study, we performed membrane potential recording from neurons in the vicinity of pipettes for field potential recording. We found that the rhythmic bursts in the VMH were preserved in low Ca2+/high Mg2+ synaptic transmission blockade solution. During membrane hyperpolarization by current injection, the action potential was largely inhibited, but fluctuation of the membrane potential remained with a frequency similar to that at resting potential level. The electric VMH oscillation disappeared after application of either a gap junction blocker, carbenoxolone (100µM), or a persistent sodium channel blocker, riluzole (20µM). Membrane potentials and input resistances of rhythmic burst neurons in the VMH were not significantly changed during these manipulations. A calcium imaging study revealed that all VMH cells exhibiting synchronized rhythmic activity detected by intracellular calcium increases were silenced following the application of carbenoxolone. These results suggest that VMH oscillation arises from the activation of persistent sodium channels and coupling via gap junctions.

Sex- and age-specific differences in the use of antiarrhythmic therapies among atrial fibrillation patients: a nationwide cohort study.

Atrial fibrillation (AF) patients frequently require active rhythm control therapy to maintain sinus rhythm and reduce symptom burden. Our study assessed whether antiarrhythmic therapies (AATs) are used disproportionately between men and women after new-onset AF. The nationwide Finnish anticoagulation in atrial fibrillation (FinACAF) registry-based linkage study covers all patients with new-onset AF in Finland during 2007-2018. Study outcomes included initiation of AATs in the form of antiarrhythmic drugs (AAD), cardioversion, or catheter ablation. The study population constituted of 229 565 patients (50% females). Women were older than men (76.6 ± 11.8 vs. 68.9 ± 13.4 years) and had higher prevalence of hypertension or hyperthyroidism, but lower prevalence of vascular disease, diabetes, renal disease, and cardiomyopathies than men. Overall, 17.6% of women and 25.1% of men were treated with any AAT. Women were treated with AADs more often than men in all age groups (adjusted subdistribution hazard ratio (aSHR) 1.223, 95%-CI 1.187-1.261). Cardioversions were also performed less often on women than on men aged <65 years (aSHR 0.722, 95%-CI 0.695-0.749), more often in patients ≥75 years (aSHR 1.166, 95%-CI 1.108-1.227), while no difference between the sexes existed in patients aged 65-74 years. Ablations were performed less often in women aged <65 years (aSHR 0.908, 95%-CI 0.826-0.998) and ≥75 years (aSHR 0.521, 95%-CI 0.354-0.766), whereas there was no difference in patients aged 65-74 years. Women used more AAD than men in all age groups but underwent fewer cardioversion and ablation procedures when aged <65 years.

Discovering temporal-spatial features of jobs-housing relationship from a regional perspective: A nationwide study

The recent developments in regionalization have redefined the concept of jobs-housing relationship, calling for reexaminations from the regional perspective. This paper studies the temporal and spatial features of jobs-housing relationship and their relations with regional mobility and regional structure in 2258 Quxians (urban districts or rural counties) across China based on 49 months of cellular signaling data. Results show that jobs-housing relationship differ between city types and have seasonal cycles and yearly trends reflecting the rhythm and development of human activity. The temporal variations in jobs-housing relationship are affected by regional mobility, and larger intercity travel volume leads to lower balance level. The spatial variations in jobs-housing relationship are influenced by the form of regional structure, as measured using the Zipf scaling exponent. More polarized regions are less balanced with exceptions in underdeveloped regions. There is an underlying inflection point in jobs-housing relationship that is similar to its long-term average value and reflects regional market equilibrium. This paper contributes to existing literature by providing a big-data driven nationwide jobs-housing study fully aware of the theoretical and practical needs of a regionalizing world. Findings advances our understanding of macroscopic jobs-housing relationship, and offers policy suggestions for governments across the globe.

Neuropeptide-dependent spike time precision and plasticity in circadian output neurons.

Circadian rhythms influence various physiological and behavioral processes such as sleep-wake cycles, hormone secretion, and metabolism. Circadian output neurons are a group of neurons that receive input from the central circadian clock located in the suprachiasmatic nucleus of the mammalian brain and transmit timing information to different regions of the brain and body, coordinating the circadian rhythms of various physiological processes. In Drosophila , an important set of circadian output neurons are called pars intercerebralis (PI) neurons, which receive input from specific clock neurons called DN1. These neurons can further be subdivided into functionally and anatomically distinctive anterior (DN1a) and posterior (DN1p) clusters. The neuropeptide diuretic hormones 31 (Dh31) and 44 (Dh44) are the insect neuropeptides known to activate PI neurons to control activity rhythms. However, the neurophysiological basis of how Dh31 and Dh44 affect circadian clock neural coding mechanisms underlying sleep in Drosophila is not well understood. Here, we identify Dh31/Dh44-dependent spike time precision and plasticity in PI neurons. We find that the application of synthesized Dh31 and Dh44 affects membrane potential dynamics of PI neurons in the precise timing of the neuronal firing through their synergistic interaction, possibly mediated by calcium-activated potassium channel conductance. Further, we characterize that Dh31/Dh44 enhances postsynaptic potentials in PI neurons. Together, these results suggest multiplexed neuropeptide-dependent spike time precision and plasticity as circadian clock neural coding mechanisms underlying sleep in Drosophila .

Experimentally Elevated Levels of Testosterone Advance Daily Onset of Activity in Short-Day Housed Male House Sparrows (Passer domesticus).

Seasonal changes in sleep/wake cycles and behaviors related to reproduction often co-occur with seasonal fluctuations in sex hormones. Experimental studies have established that fluctuations in circulating testosterone mediate circadian rhythms. However, most studies are performed under constant lighting conditions and fail to investigate the effects of testosterone on the phenotypic output of circadian rhythms, that is, chronotype (daily activity patterns under light:dark cycles). Here, we experimentally elevated testosterone with implants during short nonbreeding daylengths in male house sparrows (Passer domesticus) to test if observed seasonal changes in chronotype are directly in response to photoperiod or to testosterone. We fitted individuals with accelerometers to track activity across treatment periods. Birds experienced three treatments periods: short day photoperiods before manipulation (SD), followed by testosterone implants while still on short days (SD + T). Implants were then removed. After a decrease in cloacal protuberance size, an indicator of low testosterone levels, birds were then photostimulated on long days (LD). Blood samples were collected at night, when testosterone peaks, to compare testosterone levels to daily onset/offset activity for experimental periods. Our results indicate that experimentally elevated testosterone under short nonbreeding photoperiods significantly advanced daily onset of activity and total daily activity relative to daylength. This suggests that testosterone, independent of photoperiod, is responsible for seasonal shifts in chronotypes and daily activity rhythms. These findings suggest that sex steroid hormone actions regulate timing of daily behaviors, likely coordinating expression of reproductive behaviors to appropriate times of the day.

Sex-Related Variation in Circadian Rhythms in the Bumble Bee Bombus terrestris.

Mating success depends on many factors, but first of all, a male and a female need to meet at the same place and time. The circadian clock is an endogenous system regulating activity and sex-related behaviors in animals. We studied bumble bees (Bombus terrestris) in which the influence of circadian rhythms on sexual behavior has been little explored. We characterized circadian rhythms in adult emergence and locomotor activity under different illumination regimes for males and gynes (unmated queens). We developed a method to monitor adult emergence from the pupal cocoon and found no circadian rhythms in this behavior for either males or gynes. These results are not consistent with the hypothesis that the circadian clock regulates emergence from the pupa in this species. Consistent with this premise, we found that both gynes and males do not show circadian rhythms in locomotor activity during the first 3 days after pupal emergence, but shortly after developed robust circadian rhythms that are readily shifted by a phase delay in illumination regime. We conclude that the bumble bees do not need strong rhythms in adult emergence and during early adult life in their protected and regulated nest environment, but do need strong activity rhythms for timing flights and mating-related behaviors. Next, we tested the hypothesis that the locomotor activity of males and gynes have a similar phase, which may improve mating success. We found that both males and gynes have strong endogenous circadian rhythms that are entrained by the illumination regime, but males show rhythms at an earlier age, their rhythms are stronger, and their phase is slightly advanced relative to that of gynes. An earlier phase may be advantageous to males competing to mate a receptive gyne. Our results are consistent with the hypothesis that sex-related variations in circadian rhythms is shaped by sexual selection.

7503 Light Composition Alters Feline Stress in a Shelter Environment

Abstract Disclosure: A.M. Yaw: None. M.E. Gardella: None. J. Jacobs: None. H.M. Hoffmann: None. Millions of cats enter animal shelters each year. Unfortunately, due to high numbers of cats entering shelters and limited physical housing space, over 50% of healthy and adoptable cats with extended shelter stays are euthanized yearly. While animal shelters are essential for keeping cats safe from unfit living conditions, they are a stressful environment. High stress in cats increases health risks and undesirable behaviors and is associated with reduced adoptions. Given the role of light in regulating hormonal stress responses and behavior, we partnered with a Midwestern animal control and shelter to evaluate how light intensity and light composition impact feline behavior and urinary cortisol levels in 123 domestic cats (Felis catus; 65 male and 58 female). The impact of three lighting conditions, white, dim, and orange (blue-depleted) light, were evaluated for the first 5-6 days following admittance into the shelter. Individually housed adults (8 months-10 years) were outfitted with PetPace Smart Collars to evaluate locomotor activity, and cat stress was evaluated daily through urine samples and a behavioral approach test. All data were analyzed by experimenters who were blind to the groups and tested via one or two-way ANOVA or repeated measures mixed-effects model with Geisser-Greenhouse correction. Urinary cortisol levels were dependent on both light quality and day in shelter, where cats under orange light had reduced cortisol on days 4-5 in the shelter compared to cats in standard lighting. Light quality also altered cat hiding behavior, such that the percentage of cats hiding was increased on dim light compared to both standard and orange light. A novel behavioral approach task found reduced cat stress on days 4-5 in standard and orange light; however, dim light increased cat stress on day 5 in shelter. All cats exhibited circadian rhythms in locomotor activity with periods ranging from 21.33-35.67h independent of light condition and day in shelter, and locomotor activity increased on days 3-4 compared to day 2 in the shelter, with no effect of light condition. There were no sex differences in in hiding, PetPace activity, or cat stress scores under any light condition; however, females displayed increased urinary cortisol levels compared to males in standard, but not dim or orange, light. This shows for the first time that room light manipulation can help shelters enact easy and inexpensive changes that make the adjustment period shorter and less stressful for incoming cats which will improve animal wellbeing. Presentation: 6/1/2024

7861 Estrogen Receptor Alpha Regulates the Sex Difference in Jet Lag in Mice

Abstract Disclosure: M.A. Venegas: None. N. Westray: None. J.S. Pendergast: None. The circadian system aligns 24-hour cycles of internal biological processes with the environmental light-dark cycle. Abrupt shifts in the timing of the light-dark cycle that occur during travel across time zones misalign internal circadian clocks with the environment and cause jet lag. The symptoms of jet lag subside when circadian clocks resynchronize to the new light-dark cycle. Female mice in proestrus resynchronize to shifted light-dark cycles faster than males. The objective of this study was to investigate the estrogen signaling mechanisms underlying this sex difference in jet lag in mice. We measured wheel-running activity rhythms in C57BL/6J male and female wild-type (WT) and ERα knockout (ERαKO) mice. Female WT mice had 2-fold greater daily activity than male mice. Disabling the function of ERα ablated the sex difference in daily activity; both male and female ERαKO mice had markedly reduced activity compared to WT mice. Next, we advanced the timing of the light-dark cycle by 6 hours to simulate eastward travel. Female WT mice resynchronized to the new light-dark cycle faster than WT males. This sex difference was abolished in ERαKO mice. The rate of resynchronization was slower in female ERaKO mice compared to WT females and was indistinguishable from males. We next investigated 2 putative mechanisms underlying the accelerated rate of resynchronization in WT females. First, mice with faster endogenous clocks resynchronize to new light-dark cycles faster. However, we found that the velocity of the endogenous clock (circadian period) did not differ between WT and ERαKO male and female mice. Second, mice with greater phase advances to light exposure in the late night also resynchronize faster. To determine the magnitude of phase advances, we housed mice in constant darkness and then exposed them to a 15-minute light pulse during the late subjective night. We found no differences in the magnitudes of phase shifts between WT and ERαKO male and female mice. Together these studies show that ERα regulates the rate of resynchronization to shifted light-dark cycles in female mice but does not do so by altering conventional circadian rhythm parameters. Uncovering the mechanisms underlying the sex difference in resynchronization to shifted light-dark cycles can be used to develop strategies to alleviate jet lag and shift work symptoms. Presentation: 6/3/2024

Chunk Duration Limits the Learning of Multiword Chunks: Behavioral and Electroencephalogram Evidence from Statistical Learning.

Language comprehension involves the grouping of words into larger multiword chunks. This is required to recode information into sparser representations to mitigate memory limitations and counteract forgetting. It has been suggested that electrophysiological processing time windows constrain the formation of these units. Specifically, the period of rhythmic neural activity (i.e., slow-frequency neural oscillations) may set an upper limit of 2-3 sec. Here, we assess whether learning of new multiword chunks is also affected by this neural limit. We applied an auditory statistical learning paradigm of an artificial language while manipulating the duration of to-be-learnt chunks. Participants listened to isochronous sequences of disyllabic pseudowords from which they could learn hidden three-word chunks based on transitional probabilities. We presented chunks of 1.95, 2.55, and 3.15 sec that were created by varying the pause interval between pseudowords. In a first behavioral experiment, we tested learning using an implicit target detection task. We found better learning for chunks of 2.55 sec as compared to longer durations in line with an upper limit of the proposed time constraint. In a second experiment, we recorded participants' electroencephalogram during the exposure phase to use frequency tagging as a neural index of statistical learning. Extending the behavioral findings, results show a significant decline in neural tracking for chunks exceeding 3 sec as compared to both shorter durations. Overall, we suggest that language learning is constrained by endogenous time constraints, possibly reflecting electrophysiological processing windows.

Daily Activity Rhythms of Animals in the Southwest Mountains, China: Influences of Interspecific Relationships and Seasons

Temporal and spatial factors regulate the interactions between apex predators, mesocarnivores, and herbivores. Prey adjust their activity patterns and spatial utilization based on predator activities; in turn, predators also adapt to the activities of their prey. To elucidate the factors influencing the daily activity rhythms of animals, 115 camera traps were established from September 2019 to June 2023 to assess the influences of interspecific relationships and seasons on the daily activity rhythms of animals in the southwest mountains of China. The species captured by the cameras included six Carnivora (such as Panthera pardus and Lynx lynx), six Artiodactyla (such as Moschus spp. and Rusa unicolor), one Primate (Macaca mulatta), and two Galliformes (Crossoptilon crossoptilon, Ithaginis cruentus). The results demonstrated that the 15 species exhibited different activity rhythms and peak activities to reduce intense resource competition. There were differences in the species’ activity rhythms in different seasons, with competition among different species being more intense in the cold season than in the warm season. In predation relationships, the overlap coefficient in the cold season exceeded that of the warm season, possibly due to the abundant resources in summer and food scarcity in winter. In competitive relationships, 15 pairs of species exhibited significantly higher overlap coefficients in the cold season compared to the warm season, possibly due to increased demands for energy during the cold period or seasonal changes in predatory behavior. By analyzing the daily and seasonal activity patterns of dominant species in the study area, temporal niche overlaps were established to compare the competition levels between species. These findings indicate that the activity rhythms of the animals in this area not only result from evolutionary adaptation but are also influenced by season, food resources, and interspecific relationships (predation and competition). Thus, efforts should be made to reduce human interference, protect food resources in the winter, and monitor animals’ interspecific relationships to protect animal diversity and maintain the stability of the ecosystem in this biodiversity hotspot in China.

Diminished circadian and ultradian rhythms of human brain activity in pathological tissue in vivo

Chronobiological rhythms, such as the circadian rhythm, have long been linked to neurological disorders, but it is currently unknown how pathological processes affect the expression of biological rhythms in the brain. Here, we use the unique opportunity of long-term, continuous intracranially recorded EEG from 38 patients (totalling 6338 hours) to delineate circadian (daily) and ultradian (minute to hourly) rhythms in different brain regions. We show that functional circadian and ultradian rhythms are diminished in pathological tissue, independent of regional variations. We further demonstrate that these diminished rhythms are persistent in time, regardless of load or occurrence of pathological events. These findings provide evidence that brain pathology is functionally associated with persistently diminished chronobiological rhythms in vivo in humans, independent of regional variations or pathological events. Future work interacting with, and restoring, these modulatory chronobiological rhythms may allow for novel therapies.

Chronobiological Spatial Clusters of Cortical Regions in the Human Brain.

We demonstrate that different regions of the cerebral cortex have different diurnal rhythms of spontaneously occurring high-frequency oscillations (HFOs). High-frequency oscillations were assessed with standard-of-care stereotactic electroencephalography in patients with drug-resistant epilepsy. To ensure generalizability of our findings beyond patients with drug-resistant epilepsy, we excluded stereotactic electroencephalography electrode contacts lying within seizure-onset zones, epileptogenic lesions, having frequent epileptiform activity, and excessive artifact. For each patient, we evaluated twenty-four 5-minute stereotactic electroencephalography epochs, sampled hourly throughout the day, and obtained the HFO rate (number of HFOs/minute) in every stereotactic electroencephalography channel. We analyzed diurnal rhythms of the HFO rates with the cosinor model and clustered neuroanatomic parcels in a standard brain space based on similarity of their cosinor parameters. Finally, we compared overlap among resting-state networks, described in the neuroimaging literature, and chronobiological spatial clusters discovered by us. We found five clusters that localized predominantly or exclusively to the left perisylvian, left perirolandic and left temporal, right perisylvian and right parietal, right frontal, and right insular-opercular cortices, respectively. These clusters were characterized by similarity of the HFO rates according to the time of the day. Also, these chronobiological spatial clusters preferentially overlapped with specific resting-state networks, particularly default mode network (clusters 1 and 3), frontoparietal network (cluster 1), visual network (cluster 1), and mesial temporal network (cluster 2). This is probably the first human study to report clusters of cortical regions with similar diurnal rhythms of electrographic activity. Overlap with resting-state networks attests to their functional significance and has implications for understanding cognitive functions and epilepsy-related mortality.

Molecular and Cellular Mechanisms of Motor Circuit Development.

Motor circuits represent the main output of the central nervous system and produce dynamic behaviors ranging from relatively simple rhythmic activities like swimming in fish and breathing in mammals to highly sophisticated dexterous movements in humans. Despite decades of research, the development and function of motor circuits remain poorly understood. Breakthroughs in the field recently provided new tools and tractable model systems that set the stage to discover the molecular mechanisms and circuit logic underlying motor control. Here, we describe recent advances from both vertebrate (mouse, frog) and invertebrate (nematode, fruit fly) systems on cellular and molecular mechanisms that enable motor circuits to develop and function and highlight conserved and divergent mechanisms necessary for motor circuit development.

Challenges and Approaches in the Study of Neural Entrainment.

When exposed to rhythmic stimulation, the human brain displays rhythmic activity across sensory modalities and regions. Given the ubiquity of this phenomenon, how sensory rhythms are transformed into neural rhythms remains surprisingly inconclusive. An influential model posits that endogenous oscillations entrain to external rhythms, thereby encoding environmental dynamics and shaping perception. However, research on neural entrainment faces multiple challenges, from ambiguous definitions to methodological difficulties when endogenous oscillations need to be identified and disentangled from other stimulus-related mechanisms that can lead to similar phase-locked responses. Yet, recent years have seen novel approaches to overcome these challenges, including computational modeling, insights from dynamical systems theory, sophisticated stimulus designs, and study of neuropsychological impairments. This review outlines key challenges in neural entrainment research, delineates state-of-the-art approaches, and integrates findings from human and animal neurophysiology to provide a broad perspective on the usefulness, validity, and constraints of oscillatory models in brain-environment interaction.

Effects of 8 weeks of rhythmic physical activity on gross motor movements in 4-5-year-olds: A randomized controlled trial

ObjectiveRhythmic physical activity holds promise for positively influencing the gross motor development of 4-5-year-old children, yet empirical research in this domain remains limited. This study aimed to investigate the effects of rhythmic physical activity on the gross motor development in children aged 4–5 years. MethodsFifty children aged 4–5 years were recruited and randomly assigned to either the intervention or control group. Both groups participated in a 10-week intervention program facilitated by a professional trainer, with support from numerous dedicated volunteers from reputable sports universities. This program comprised a one-week baseline assessment followed by 8 weeks of rhythmic physical activity training conducted three times per week. Gross motor performance was assessed using the PGMQ scale before and one week after the intervention. ResultsFollowing the 8-week intervention, the intervention group demonstrated significant enhancements in displacement ability, with notable improvements observed in. Specifically, the scores for running, sliding lateral transfer, leaping step, two-footed back-and-forth jump, and total displacement ability showed significant increases (P < 0.05). Moreover, the total scores for running, standing long jump, sliding lateral transfer, leaping step, two-footed back-and-forth jump, and displacement ability exhibited significant differences between the intervention and control groups (P < 0.05). Regarding manipulative ability, the intervention group showed significant increases in scores for over-the-shoulder throwing, two-handed catching, and kicking (P < 0.05). Moreover, there were significant differences between groups in the scores for two-handed catching and kicking (P < 0.05). Concerning balance ability, the intervention group exhibited significant improvements in scores for single-leg stand, double-leg stand, and total balance ability (P < 0.05). No significant differences were observed in any of the indices within the control group (P > 0.05). The two-way repeated measures ANOVA of intervention × time revealed significant differences in scores for running, sliding lateral movement, leaping step, jumping back and forth with both feet, leading ability, kicking, manipulation ability, single-leg stand, double-leg stand, balance ability, and gross motor scores (P < 0.05). ConclusionsThis study underscores the beneficial impact of engaging in eight weeks of rhythmic physical activity on the gross motor development of 4-5-year-olds. Furthermore, the improvements in gross motor development achieved through rhythmic physical activity may surpass those obtained through general physical activity.