Dietary restriction modulates ultradian rhythms and autocorrelation properties in mice behavior.

Animal behavior emerges from integration of many processes with different spatial and temporal scales. Dynamical behavioral patterns, including daily and ultradian rhythms and the dynamical microstructure of behavior (i.e., autocorrelations properties), can be differentially affected by external cues. Identifying these patterns is important for understanding how organisms adapt to their environment, yet unbiased methods to quantify dynamical changes over multiple temporal scales are lacking. Herein, we combine a wavelet approach with Detrended Fluctuation Analysis to identify behavioral patterns and evaluate changes over 42-days in mice subjected to different dietary restriction paradigms. We show that feeding restriction alters dynamical patterns: not only are daily rhythms modulated but also the presence, phase and/or strength of ~12h-rhythms, as well as the nature of autocorrelation properties of feed-intake and wheel running behaviors. These results highlight the underlying complexity of behavioral architecture and offer insights into the multi-scale impact of feeding habits on physiology.

Seasonal Influence on Salivary Myeloperoxidase Diurnal Variations in Young Healthy Subjects: A Preliminary Study.

BACKGROUND: The interaction between oxidative status markers and biological rhythms is considered particularly important in the pathogenesis of many diseases and more effective therapies. We aimed to determine if the salivary secretion of myeloperoxidase exhibits diurnal variations, and if the potential daily variability differs seasonally. METHODS: The study was performed in Poznan, Poland (52,25°N, 16,58°E) in 10 healthy male volunteers (age median 23.5 years). Whole mixed unstimulated saliva was collected in summer (August) and winter (December) during 36 h at 2-h intervals starting at 6 a.m. on Saturday and ending at 6 p.m. on Sunday, in the domestic setting. The samples were analysed for myeloperoxidase (MPO) and cortisol by immunoassays. The presence of the circadian rhythm of cortisol secretion in saliva confirmed the rhythmicity of the volunteers. RESULTS: For salivary MPO, significantly higher concentrations compared to midnight and noon were observed for 4 a.m. in both summer and winter. Using the cosinor analysis, the variations in salivary MPO levels showed a moderate fit for the 12-h period rhythm (acrophases: in summer 05:37/17:37, in winter 06:16/18:16), without significant differences in the rhythm parameters in summer and winter. However, higher self-reported Global Seasonal Score (which may predispose to seasonal affective disorder) was associated with significantly stronger relative amplitude (RS = 0.811) in winter season only. CONCLUSIONS: In conclusion, our findings suggest the possible ultradian rhythm for MPO in saliva, with two peaks during the day, regardless of the season.

Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial.

BACKGROUND: Primary adrenal insufficiency (PAI) mortality and morbidity remain unacceptably high, possibly arising as glucocorticoid replacement does not replicate natural physiology. A pulsatile subcutaneous pump can closely replicate cortisol's circadian and ultradian rhythm. OBJECTIVES: To assess the effect of pump therapy on quality of life, mood, functional neuroimaging, behavioural/cognitive responses, sleep and metabolism. METHODS: A 6-week randomised, crossover, double-blinded and placebo-controlled feasibility study of usual dose hydrocortisone in PAI administered as either pulsed subcutaneous or standard care in Bristol, United Kingdom (ISRCTN67193733). Participants were stratified by adrenal insufficiency type. All participants who received study drugs are included in the analysis. The primary outcome, the facial expression recognition task (FERT), occurred at week 6. RESULTS: Between December 2014 and 2017, 22 participants were recruited - 20 completed both arms, and 21 were analysed. The pump was well-tolerated. No change was seen in the FERT primary outcome; however, there were subjective improvements in fatigue and mood. Additionally, functional magnetic resonance imaging revealed differential neural processing to emotional cues and visual stimulation. Region of interest analysis identified the left amygdala and insula, key glucocorticoid-sensitive regions involved in emotional ambiguity. FERT post hoc analysis confirmed this response. There were four serious adverse events (AE): three intercurrent illnesses requiring hospitalisation (1/3, 33.3% pump) and a planned procedure (1/1, 100% pump). There was a small number of expected AEs: infusion site bruising/itching (3/5, 60% pump), intercurrent illness requiring extra (3/7, 42% pump) and no extra (4/6, 66% pump) steroid. CONCLUSIONS: These findings support the administration of hormone therapy that mimics physiology.

Personalized Non-contact Sleep Stage Estimation with Weighted Probability Estimation by Ultradian Rhythm.

This paper focused on ultradian rhythms (a sleep cycle of approximately 60 to 120 minute) for personalizing sleep stage estimation, and proposed a personalized sleep stage estimation method that weights the results estimated by machine learning with the predicted ultradian rhythms. The ultradian rhythms are predicted by the body movement density which is correlated with ultradian rhythm. To investigate the effectiveness of the proposed method, this paper conducts human subjects experiment for eight subjects.Clinical relevance- The proposed method is compared with the results estimated by conventional ML, and the result of the proposed method is competitive with their conventional counterparts. This indicates that the ultradian rhythm has the potential for developing personalized sleep stage estimation.

Temporal dynamics and composition of ocular surface microbiota in C57BL/6J mice: uncovering a 12h ultradian rhythm.

Purpose: This study aimed to investigate the presence of rhythmic fluctuations in the composition, abundance, and functions of commensal core bacteria on the ocular surface of C57BL/6J mice. Methods: Male C57BL/6J mice, aged 12 weeks, were subjected to a 12-hour light/12-hour dark cycle. Ocular surface tissue samples were collected at four time points (ZT) over a 24-hour period at six-hour intervals. The core ocular surface microbiota's oscillation cycles and frequencies were assessed using 16S rRNA gene sequencing targeting the V3-V4 region, along with the JTK_CYCLE algorithm. Functional predictions of these bacteria were conducted using PICRUSt2. Results: Deep sequencing of the ocular surface microbiota highlighted the high abundance of commensal bacteria, with Proteobacteria, Actinobacteriota, and Firmicutes collectively constituting over 90% of the total sample abundance. Among the 22 core bacterial genera, 11 exhibited robust 12-hour rhythms, including Halomonas, Pelagibacterium, Pseudomonas, Nesterenkonia, norank_f_Hyphomonadaceae, Stenotrophomonas, Anoxybacillus, Acinetobacter, Zoogloea, Brevibacillus, and Ralstonia. Further taxonomic analysis indicated significant intra-cluster similarities and inter-cluster differences at the order, family, and genus levels during ZT0/12 and ZT6/18. Community interaction networks and functional prediction analyses revealed synchronized 12-hour rhythmic oscillations in neural, immune, metabolic, and other pathways associated with symbiotic bacteria. Conclusion: This study demonstrates the presence of ultradian rhythmic oscillations in commensal bacteria on the ocular surface of normal C57BL/6J mice, with a 12-hour cycle. These findings suggest a crucial role for ultradian rhythms in maintaining ocular surface homeostasis in the host.

Ultradian rhythms: Life's dance to the music of time.

A recent and updated translation of a book, earlier published in Russian in 2021, contains a fascinating account of the development of a central theme in our understanding of the kinetics of cellular growth and development (Brodsky 2022). The book deals with the twin concepts of ultradian (i.e. about one hour period) signals and cellto-cell communication. The author, Vsevolod Ya. Brodsky, has performed a major service by discussing in a comprehensive manner studies on high-frequency oscillations in intercellular communication. The book will be especially valuable to readers who are not familiar with the extensive Russian literature on the subject, much of which has been ignored elsewhere. The present Commentary uses it as a take-off point in order to highlight issues that are common to the area of biological rhythms generally and ultradian oscillations in particular. In view of the importance of the book, we critique it towards the latter part of the Commentary in the style of a book review.

Effect of Heliogeophysical and Atmospheric Factors on the Degree of Synchronization of Ultradian Rhythms of Body Temperature in Mice.

In a long-term (8 months) study, we examined the degree of synchronization of ultradian body temperature oscillations of two isolated groups of mice kept under constant dim illumination. In most cases, the periods of increased activity accompanied by rapid elevation of body temperature coincided in these groups of mice, but in some days, no significant synchronization between the examined parameters was observed. Analysis of the effects of environmental factors on the degree of synchronization of ultradian rhythms in mice revealed association of this parameter with the dynamics of atmospheric pressure (AtmP) and to a lesser extent with the vertical component of interplanetary magnetic field Bz. The loss in synchronicity of ultradian rhythms of mouse activity occurred after a rapid drop of AtmP or during pronounced negative Bz. Therefore, these factors can be viewed as desynchronizers of the biological ultradian rhythms.

Analysis of Association of Ultradian Body Temperature Rhythms in Animals with Intensity of Fluctuations of Radioactive Decay of Natural 40K Isotope.

The study monitored the long-term body temperature (BT) oscillations of C57BL/6 mice and outbred starlings (Sturnus vulgaris) to compare them with fluctuation in decay rate of radioactive natural 40K isotope. The spectrum analysis revealed simultaneous changes of the predominant periods in BT spectra of the animals and those in fluctuation in 40K decay rate. A positive correlation was established between BT dynamics and fluctuation in decay rate. The superposed epoch analysis revealed predominant coincidence of the moments of BT and fluctuation in 40K decay rate. The novel data indicate association between BT ultradian rhythms with quasirhythmic variations of fluctuation in 40K decay rate.

A dynamically coherent pattern of rhythms that matches between distant species across the evolutionary scale.

We address the temporal organization of circadian and ultradian rhythms, crucial for understanding biological timekeeping in behavior, physiology, metabolism, and alignment with geophysical time. Using a newly developed five-steps wavelet-based approach to analyze high-resolution time series of metabolism in yeast cultures and spontaneous movement, metabolism, and feeding behavior in mice, rats, and quails, we describe a dynamically coherent pattern of rhythms spanning over a broad range of temporal scales (hours to minutes). The dynamic pattern found shares key features among the four, evolutionary distant, species analyzed. Specifically, a branching appearance given by splitting periods from 24 h into 12 h, 8 h and below in mammalian and avian species, or from 14 h down to 0.07 h in yeast. Scale-free fluctuations with long-range correlations prevail below ~ 4 h. Synthetic time series modeling support a scenario of coexisting behavioral rhythms, with circadian and ultradian rhythms at the center of the emergent pattern observed.

DEC-7/SUSD2, a sushi domain-containing protein, regulates an ultradian behavior mediated by intestinal epithelial Ca2+ oscillations in Caenorhabditis elegans.

In Caenorhabditis elegans, rhythmic posterior body wall muscle contractions mediate the highly regular defecation cycle. These contractions are regulated by inositol-1,4,5-trisphosphate (InsP3) receptor-dependent Ca2+ oscillations in intestinal epithelial cells. Here, we find that mutations in dec-7, which encodes the nematode ortholog of the human Sushi domain-containing 2 protein (SUSD2), lead to an increase in InsP3 receptor-dependent rhythmic posterior body wall muscle contractions. DEC-7 is highly expressed in the intestinal epithelia and localizes to the cell-cell junction. The increase in rhythmic activity caused by the loss of dec-7 is dependent on the innexin gap junction protein INX-16. Moreover, DEC-7 is required for the clustering of INX-16 to the cell-cell junction of the intestinal epithelia. We hypothesize that DEC-7/SUSD2 regulates INX-16 activity to mediate the rhythmic frequency of the defecation motor program. Thus, our data indicate a critical role of a phylogenetically conserved cell-cell junction protein in mediating an ultradian rhythm in the intestinal epithelia of C. elegans.NEW & NOTEWORTHY The conserved complement group protein DEC-7/SUSD2 acts at the apical cell-cell junction of C. elegans intestinal epithelia to mediate gap junction protein organization and function to facilitate a Ca2+ wave-regulated ultradian behavior.

Physiological Rhythms and Biological Variation of Biomolecules: The Road to Personalized Laboratory Medicine.

The concentration of biomolecules in living systems shows numerous systematic and random variations. Systematic variations can be classified based on the frequency of variations as ultradian (<24 h), circadian (approximately 24 h), and infradian (>24 h), which are partly predictable. Random biological variations are known as between-subject biological variations that are the variations among the set points of an analyte from different individuals and within-subject biological variation, which is the variation of the analyte around individuals' set points. The random biological variation cannot be predicted but can be estimated using appropriate measurement and statistical procedures. Physiological rhythms and random biological variation of the analytes could be considered the essential elements of predictive, preventive, and particularly personalized laboratory medicine. This systematic review aims to summarize research that have been done about the types of physiological rhythms, biological variations, and their effects on laboratory tests. We have searched the PubMed and Web of Science databases for biological variation and physiological rhythm articles in English without time restrictions with the terms "Biological variation, Within-subject biological variation, Between-subject biological variation, Physiological rhythms, Ultradian rhythms, Circadian rhythm, Infradian rhythms". It was concluded that, for effective management of predicting, preventing, and personalizing medicine, which is based on the safe and valid interpretation of patients' laboratory test results, both physiological rhythms and biological variation of the measurands should be considered simultaneously.

Co-expression of diurnal and ultradian rhythms in the plasma metabolome of common voles (Microtus arvalis).

Metabolic rhythms include rapid, ultradian (hourly) dynamics, but it remains unclear what their relationship to circadian metabolic rhythms is, and what role meal timing plays in coordinating these ultradian rhythms in metabolism. Here, we characterized widespread ultradian rhythms under ad libitum feeding conditions in the plasma metabolome of the vole, the gold standard animal model for behavioral ultradian rhythms, naturally expressing ~2-h foraging rhythms throughout the day and night. These ultradian metabolite rhythms co-expressed with diurnal 24-h rhythms in the same metabolites and did not align with food intake patterns. Specifically, under light-dark entrained conditions we showed twice daily entrainment of phase and period of ultradian behavioral rhythms associated with phase adjustment of the ultradian cycle around the light-dark and dark-light transitions. These ultradian activity patterns also drove an ultradian feeding pattern. We used a unique approach to map this behavioral activity/feeding status to high temporal resolution (every 90 min) measures of plasma metabolite profiles across the 24-h light-dark cycle. A total of 148 known metabolites were detected in vole plasma. Supervised, discriminant analysis did not group metabolite concentration by feeding status, instead, unsupervised clustering of metabolite time courses revealed clusters of metabolites that exhibited significant ultradian rhythms with periods different from the feeding cycle. Two clusters with dissimilar ultradian dynamics, one lipid-enriched (period = 3.4 h) and one amino acid-enriched (period = 4.1 h), both showed co-expression with diurnal cycles. A third cluster solely comprised of glycerophospholipids (specifically ether-linked phosphatidylcholines) expressed an 11.9 h ultradian rhythm without co-expressed diurnal rhythmicity. Our findings show coordinated co-expression of diurnal metabolic rhythms with rapid dynamics in feeding and metabolism. These findings reveal that ultradian rhythms are integral to biological timing of metabolic regulation, and will be important in interpreting the impact of circadian desynchrony and meal timing on metabolic rhythms.

Twelve-hour rhythms in transcript expression within the human dorsolateral prefrontal cortex are altered in schizophrenia.

Twelve-hour (12 h) ultradian rhythms are a well-known phenomenon in coastal marine organisms. While 12 h cycles are observed in human behavior and physiology, no study has measured 12 h rhythms in the human brain. Here, we identify 12 h rhythms in transcripts that either peak at sleep/wake transitions (approximately 9 AM/PM) or static times (approximately 3 PM/AM) in the dorsolateral prefrontal cortex, a region involved in cognition. Subjects with schizophrenia (SZ) lose 12 h rhythms in genes associated with the unfolded protein response and neuronal structural maintenance. Moreover, genes involved in mitochondrial function and protein translation, which normally peak at sleep/wake transitions, peak instead at static times in SZ, suggesting suboptimal timing of these essential processes.

Beyond circadian rhythms: emerging roles of ultradian rhythms in control of liver functions.

The mammalian liver must cope with various metabolic and physiological changes that normally recur every day and primarily stem from daily cycles of rest-activity and fasting-feeding. Although a large body of evidence supports the reciprocal regulation of circadian rhythms and liver function, the research on the hepatic ultradian rhythms have largely been lagging behind. However, with the advent of more cost-effective high-throughput omics technologies, high-resolution time-lapse imaging, and more robust and powerful mathematical tools, several recent studies have shed new light on the presence and functions of hepatic ultradian rhythms. In this review, we will first very briefly discuss the basic principles of circadian rhythms, and then cover in greater details the recent literature related to ultradian rhythms. Specifically, we will highlight the prevalence and mechanisms of hepatic 12-h rhythms, and 8-h rhythms, which cycle at the second and third harmonics of circadian frequency. Finally, we also refer to ultradian rhythms with other frequencies and examine the limitations of the current approaches as well as the challenges related to identifying ultradian rhythm and addressing their molecular underpinnings.

Modified Wavelet Analyses Permit Quantification of Dynamic Interactions Between Ultradian and Circadian Rhythms.

Circadian rhythms provide daily temporal structure to cellular and organismal biological processes, ranging from gene expression to cognition. Higher-frequency (intradaily) ultradian rhythms are similarly ubiquitous but have garnered far less empirical study, in part because of the properties that define them-multimodal periods, non-stationarity, circadian harmonics, and diurnal modulation-pose challenges to their accurate and precise quantification. Wavelet analyses are ideally suited to address these challenges, but wavelet-based measurement of ultradian rhythms has remained largely idiographic. Here, we describe novel analytical approaches, based on discrete and continuous wavelet transforms, which permit quantification of rhythmic power distribution across a broad ultradian spectrum, as well as precise identification of period within empirically determined ultradian bands. Moreover, the aggregation of normalized wavelet matrices allows group-level analyses of experimental treatments, thereby circumventing limitations of idiographic approaches. The accuracy and precision of these wavelet analyses were validated using in silico and in vivo models with known ultradian features. Experiments in male and female mice yielded robust and repeatable measures of ultradian period and power in home cage locomotor activity, confirming and extending reports of ultradian rhythm modulation by sex, gonadal hormones, and circadian entrainment. Seasonal changes in day length modulated ultradian period and power, and exerted opposite effects in the light and dark phases of the 24 h day, underscoring the importance of evaluating ultradian rhythms with attention to circadian phase. Sex differences in ultradian rhythms were more prominent at night and depended on gonadal hormones in male mice. Thus, relatively straightforward modifications to the wavelet procedure allowed quantification of ultradian rhythms with appropriate time-frequency resolution, generating accurate, and repeatable measures of period and power which are suitable for group-level analyses. These analytical tools may afford deeper understanding of how ultradian rhythms are generated and respond to interoceptive and exteroceptive cues.

Coupling-dependent metabolic ultradian rhythms in confluent cells.

Ultradian rhythms in metabolism and physiology have been described previously in mammals. However, the underlying mechanisms for these rhythms are still elusive. Here, we report the discovery of temperature-sensitive ultradian rhythms in mammalian fibroblasts that are independent of both the cell cycle and the circadian clock. The period in each culture is stable over time but varies in different cultures (ranging from 3 to 24 h). We show that transient, single-cell metabolic pulses are synchronized into stable ultradian rhythms across contacting cells in culture by gap junction-mediated coupling. Coordinated rhythms are also apparent for other metabolic and physiological measures, including plasma membrane potential (Δψp), intracellular glutamine, α-ketoglutarate, intracellular adenosine triphosphate (ATP), cytosolic pH, and intracellular calcium. Moreover, these ultradian rhythms require extracellular glutamine, several different ion channels, and the suppression of mitochondrial ATP synthase by α-ketoglutarate, which provides a key feedback mechanism. We hypothesize that cellular coupling and metabolic feedback can be used by cells to balance energy demands for survival.

Circadian Clock, Glucocorticoids and NF-κB Signaling in Neuroinflammation- Implicating Glucocorticoid Induced Leucine Zipper as a Molecular Link.

Inflammation including neuroinflammation is considered a protective response and is directed to repair, regenerate, and restore damaged tissues in the central nervous system. Persistent inflammation due to chronic stress, age related accrual of free radicals, subclinical infections or other factors lead to reduced survival and increased neuronal death. Circadian abnormalities secondary to altered sleep/wake cycles is one of the earliest signs of neurodegenerative diseases. Brain specific or global deficiency of core circadian trans-activator brain and muscle ARNT (Arylhydrocarbon Receptor Nuclear Translocator)-like protein 1 (BMAL1) or that of the transrepressor REV-ERBα, impaired neural function and cognitive performance in rodents. Consistently, transcripts of inflammatory cytokines and host immune responses have been shown to exhibit diurnal variation, in parallel with the disruption of the circadian rhythm. Glucocorticoids that exhibit both a circadian rhythm similar to that of the core clock transactivator BMAL1 and tissue specific ultradian rhythm are critical in the control of neuroinflammation and re-establishment of homeostasis. It is widely accepted that the glucocorticoids suppress nuclear factor-kappa B (NF-κB) mediated transactivation and suppress inflammation. Recent mechanistic elucidations suggest that the core clock components also modulate NF-κB mediated transactivation in the brain and peripheral tissues. In this review we discuss evidence for interactions between the circadian clock components, glucocorticoids and NF-κB signaling responses in the brain and propose glucocorticoid induced leucine zipper (GILZ) encoded by Tsc22d3, as a molecular link that connect all three pathways in the maintenance of CNS homeostasis as well as in the pathogenesis of neuroinflammation-neurodegeneration.

Sex Differences in Pubertal Circadian and Ultradian Rhythmic Development Under Semi-naturalistic Conditions.

Biological rhythms in core body temperature (CBT) provide informative markers of adolescent development under controlled laboratory conditions. However, it is unknown whether these markers are preserved under more variable, semi-naturalistic conditions, and whether CBT may therefore prove useful in a real-world setting. To evaluate this possibility, we examined fecal steroid concentrations and CBT rhythms from pre-adolescence (p26) through early adulthood (p76) in intact male and female Wistar rats under natural light and climate at the Stephen Glickman Field Station for the Study of Behavior, Ecology and Reproduction. Despite greater environmental variability, CBT markers of pubertal onset and its rhythmic progression were comparable with those previously reported in laboratory conditions in female rats and extend actigraphy-based findings in males. Specifically, sex differences emerged in CBT circadian rhythm (CR) power and amplitude prior to pubertal onset and persisted into early adulthood, with females exhibiting elevated CBT and decreased CR power compared with males. Within-day (ultradian rhythm [UR]) patterns also exhibited a pronounced sex difference associated with estrous cyclicity. Pubertal onset, defined by vaginal opening, preputial separation, and sex steroid concentrations, occurred later than previously reported under lab conditions for both sexes. Vaginal opening and increased fecal estradiol concentrations were closely tied to the commencement of 4-day oscillations in CBT and UR power. By contrast, preputial separation and the first rise in testosterone concentration were not associated with adolescent changes to CBT rhythms in male rats. Together, males and females exhibited unique temporal patterning of CBT and sex steroids across pubertal development, with tractable associations between hormonal concentrations, external development, and temporal structure in females. The preservation of these features outside the laboratory supports CBT as a strong candidate for translational pubertal monitoring under semi-naturalistic conditions in females.

Multiscale Time-resolved Analysis Reveals Remaining Behavioral Rhythms in Mice Without Canonical Circadian Clocks.

Circadian rhythms are internal processes repeating approximately every 24 hours in living organisms. The dominant circadian pacemaker is synchronized to the environmental light-dark cycle. Other circadian pacemakers, which can have noncanonical circadian mechanisms, are revealed by arousing stimuli, such as scheduled feeding, palatable meals and running wheel access, or methamphetamine administration. Organisms also have ultradian rhythms, which have periods shorter than circadian rhythms. However, the biological mechanism, origin, and functional significance of ultradian rhythms are not well-elucidated. The dominant circadian rhythm often masks ultradian rhythms; therefore, we disabled the canonical circadian clock of mice by knocking out Per1/2/3 genes, where Per1 and Per2 are essential components of the mammalian light-sensitive circadian mechanism. Furthermore, we recorded wheel-running activity every minute under constant darkness for 272 days. We then investigated rhythmic components in the absence of external influences, applying unique multiscale time-resolved methods to analyze the oscillatory dynamics with time-varying frequencies. We found four rhythmic components with periods of ∼17 h, ∼8 h, ∼4 h, and ∼20 min. When the ∼17-h rhythm was prominent, the ∼8-h rhythm was of low amplitude. This phenomenon occurred periodically approximately every 2-3 weeks. We found that the ∼4-h and ∼20-min rhythms were harmonics of the ∼8-h rhythm. Coupling analysis of the ridge-extracted instantaneous frequencies revealed strong and stable phase coupling from the slower oscillations (∼17, ∼8, and ∼4 h) to the faster oscillations (∼20 min), and weak and less stable phase coupling in the reverse direction and between the slower oscillations. Together, this study elucidated the relationship between the oscillators in the absence of the canonical circadian clock, which is critical for understanding their functional significance. These studies are essential as disruption of circadian rhythms contributes to diseases, such as cancer and obesity, as well as mood disorders.

Circadian and ultradian rhythms in normal mice and in a mouse model of Huntington's disease.

Circadian rhythms in core body temperature (CBT) have been widely studied, but fewer studies have explored higher-frequency (ultradian) rhythms in detail. We analyzed CBT recordings from young and middle-aged wild-type mice as well as from the Q175 model of Huntington's disease (HD), at sufficient temporal resolution to address the question of ultradian rhythms. We used model selection methods to show that the overall circadian pattern was better fit by a square wave than a sine wave. Then, using Fourier analysis of the CBT rhythms, we identified the spectral signature of an 8-hour oscillation that occurs in the night but not the day, an observation that can be confirmed by direct inspection of the rhythms. This diurnal amplitude modulation of the 8-hour rhythm was lost with aging as well as in the HD model. Thus, the impact of aging and disease is seen here in the loss of the ability to separate rhythms into a daytime phase and a nighttime phase. These findings raise the possibility that ultradian rhythms in CBT may be a useful biomarker for the pathology within the central nervous system.