Ultradian Research Articles

Sleepy Psychotherapists: How Clinicians' Biological Factors May Affect the Conduct of Psychotherapy.

Numerous therapist variables and cognitive biases can affect the quality of the therapeutic alliance and the conduct and outcomes of psychotherapy. This article aims to examine factors that potentially affect clinician performance, including chronobiological variables of clinicians and patients. The author reviewed literature pertaining to biological influences on human cognitive performance and considered how these factors may apply to the practice of psychotherapy. Biological factors potentially affecting the conduct and quality of psychotherapy were identified. These factors include decision fatigue, hunger, sleep deficit, shift work, and several chronobiological issues related to circadian rhythms and episodic ultradian rhythms. In addition, misaligned scheduling of psychotherapy sessions in relation to therapist and patient evening-morning chronotypes may impede the effectiveness of psychotherapy. The practice of psychotherapy is cognitively demanding, requiring that clinicians remain constantly alert and in command of their executive functions. Decreases in clinician alertness resulting from homeostatic depletion, chronobiologically misaligned schedules, and illness-associated factors may reduce the quality and benefit of psychotherapy sessions. Mitigation strategies are available. Investigations of these factors are needed.

Revealing the hidden reality of the mammalian 12-h ultradian rhythms.

Biological oscillations often cycle at different harmonics of the 24-h circadian rhythms, a phenomenon we coined "Musica Universalis" in 2017. Like the circadian rhythm, the 12-h oscillation is also evolutionarily conserved, robust, and has recently gained new traction in the field of chronobiology. Originally thought to be regulated by the circadian clock and/or environmental cues, recent new evidences support the notion that the majority of 12-h rhythms are regulated by a distinct and cell-autonomous pacemaker that includes the unfolded protein response (UPR) transcription factor spliced form of XBP1 (XBP1s). 12-h cycle of XBP1s level in turn transcriptionally generates robust 12-h rhythms of gene expression enriched in the central dogma information flow (CEDIF) pathway. Given the regulatory and functional separation of the 12-h and circadian clocks, in this review, we will focus our attention on the mammalian 12-h pacemaker, and discuss our current understanding of its prevalence, evolutionary origin, regulation, and functional roles in both physiological and pathological processes.

A new ultradian rhythm in mammalian cell dry mass observed by holography

We have discovered a new 4 h ultradian rhythm that occurs during the interphase of the cell cycle in a wide range of individual mammalian cells, including both primary and transformed cells. The rhythm was detected by holographic lens-free microscopy that follows the histories of the dry mass of thousands of single live cells simultaneously, each at a resolution of five minutes. It was vital that the rhythm was observed in inherently heterogeneous cell populations, thus eliminating synchronization and labeling bias. The rhythm is independent of circadian rhythm, and is temperature-compensated. We show that the amplitude of the fundamental frequency provides a way to quantify the effects of, chemical reagents on cells, thus shedding light on its mechanism. The rhythm is suppressed by proteostasis disruptors and is detected only in proliferating cells, suggesting that it represents a massive degradation and re-synthesis of protein every 4 h in growing cells.

The relationship between early post-operative ACTH / cortisol following pituitary surgery and long-term glucocorticoid requirement - Do ultradian rhythms matter?

To determine whether early (4-8h) post-operative ACTH after trans-sphenoidal surgery (TSS) predicts long-term hypothalamic-pituitary-adrenal (HPA) axis function and to investigate early morning day 1 ACTH/cortisol variability using rapid sampling. Prospective observational study. Participants undergoing TSS were included; those treated with glucocorticoids pre-operatively received 100mg intravenous hydrocortisone on anaesthetic induction. ACTH and cortisol were measured post-operatively at+4h and+8h after induction and on day 1 every 10minutes between 0700h and 0900h. glucocorticoid requirement at 6months. Nineteen participants (10F, 9M): 6/19 (32%) were treated with replacement glucocorticoids pre-operatively; 4 had ceased by 6weeks post-operatively. One patient developed new hypopituitarism post-operatively meaning 3/19 (16%) required glucocorticoids at 6months. Post-operative+4h ACTH<14.3pmol/L (65ng/L) predicted secondary adrenal insufficiency (SAI) (sensitivity 100%, specificity 75%), whilst no participant with a post-operative+4h ACTH≥14.3pmol/L (65ng/L) required glucocorticoids at 6months. Day 1 ACTH and cortisol showed a significant circadian fall between 0700h-0900h; ACTH 4.2pmol/L (IQR 2.9-5.9) to 3.7pmol/L (IQR 2.9-5.1) P=.006 and cortisol 549nmol/L (IQR 337-618) to 439nmol/L (IQR 315-606) P<.001, with clinically insignificant ultradian secretory pulses. No participant with a post-operative+4h ACTH≥14.3pmol/L (65ng/L) required glucocorticoids at 6months; however, given only 3/19 participants had the primary outcome of interest, this must be confirmed in a larger cohort. The timing of a day 1 morning cortisol between 0700h and 0900h influences the accuracy of a single cut-off to diagnose SAI after pituitary surgery.

The use of prednisolone versus dual-release hydrocortisone in the treatment of hypoadrenalism.

The introduction of adrenocortical extract in 1930 improved the life expectancy of hyhpoadrenal patients, with further increases seen after the introduction of cortisone acetate from 1948. Most patients are now treated with synthetic hydrocortisone, and incremental advances have been made with optimisation of daily dosing and the introduction of multidose regimens. There remains a significant mortality gap between individuals with treated hypoadrenalism and the general population. It is unclear whether this gap is a result of glucocorticoid over-replacement, under-replacement or loss of the circadian and ultradian rhythm of cortisol secretion, with the risk of detrimental excess glucocorticoid exposure at later times in the day. The way forwards will involve replacement of the diurnal cortisol rhythm with better glucocorticoid replacement regimens. The steroid profile produced by both prednisolone and dual-release hydrocortisone (Plenadren), provide a smoother glucocorticoid profile of cortisol than standard oral multidose regimens of hydrocortisone and cortisone acetate. The individualisation of prednisolone doses and lower bioavailability of Plenadren offer reductions in total steroid exposure. Although there is emerging evidence of both treatments offering better cardiometabolic outcomes than standard glucocorticoid replacement regimens, there is a paucity of evidence involving very low dose prednisolone (2–4 mg daily) compared to the larger doses (~7.5 mg) historically used. Data from upcoming clinical studies on prednisolone will therefore be of key importance in informing future practice.

BIORHYTHMOLOGICAL PORTRAIT OF WORKERS OF THE DRILLING CREW IN EXTREME NORTHERN LATITUDES

Each organism at an individual level builds its system of temporary relationships with the different amplitude of oscillations - an individual biorhythmological portrait. Using Holter monitoring in the AnnaFlash2000 software in the ISCIM6 statistical processing, the ultradian rhythms of the driller crew in extreme northern latitudes studied. It revealed that the individual rhythmic processes of acrophase and cardiac rhythm bathyphase, which testify to the leading role of hypoxia, hypercapnia in adaptive mechanisms, influence the joint professional activity of small labour groups. It established that working in different biological rhythms, the driller’s team has a low degree of compatibility. The synchronization of biological rhythms in the team is achieving by the general properties of temperament as phlegmatic. More successful in adaptation - phlegmatic sanguine.

Glucocorticoid ultradian rhythmicity differentially regulates mood and resting state networks in the human brain: A randomised controlled clinical trial

Adrenal glucocorticoid secretion into the systematic circulation is characterised by a complex rhythm, composed of the diurnal variation, formed by changes in pulse amplitude of an underlying ultradian rhythm of short duration hormonal pulses. To elucidate the potential neurobiological significance of glucocorticoid pulsatility in man, we have conducted a randomised, double-blind, placebo-controlled, three-way crossover clinical trial on 15 healthy volunteers, investigating the impact of different glucocorticoid rhythms on measures of mood and neural activity under resting conditions by recruiting functional neuroimaging, computerised behavioural tests and ecological momentary assessments. Endogenous glucocorticoid biosynthesis was pharmacologically suppressed, and plasma levels of corticosteroid restored by hydrocortisone replacement in three different regimes, either mimicking the normal ultradian and circadian profile of the hormone, or retaining the normal circadian but abolishing the ultradian rhythm of the hormone, or by our current best oral replacement regime which results in a suboptimal circadian and ultradian rhythm. Our results indicate that changes in the temporal mode of glucocorticoid replacement impact (i) the morning levels of self-perceived vigour, fatigue and concentration, (ii) the diurnal pattern of mood variation, (iii) the within-network functional connectivity of various large-scale resting state networks of the human brain, (iv) the functional connectivity of the default-mode, salience and executive control networks with glucocorticoid-sensitive nodes of the corticolimbic system, and (v) the functional relationship between mood variation and underlying neural networks. The findings indicate that the pattern of the ultradian glucocorticoid rhythm could affect cognitive psychophysiology under non-stressful conditions and opens new pathways for our understanding on the neuropsychological effects of cortisol pulsatility with relevance to the goal of optimising glucocorticoid replacement strategies.

Neurotransmitters and nitric oxide are released in various brain areas according to ultradian and infradian rhythms

The push-pull superfusion technique was used to investigate release of endogenous neurotransmitters and nitric oxide in various brain regions. The transmitters catecholamines, histamine, GABA, glutamate, as well and nitric oxide are released according to ultradian rhythms which generate fluctuations of vegetative functions such as blood pressure and arousal. More frequent infradian oscillations of neurotransmitter and nitric oxide release fates are implicated in mutual interneural control.

Neurotransmitters and nitric oxide are released in various brain areas according to ultradian and infradian rhythms

The push-pull superfusion technique was used to investigate release of endogenous neurotransmitters and nitric oxide in various brain regions. The transmitters catecholamines, histamine, GABA, glutamate, as well and nitric oxide are released according to ultradian rhythms which generate fluctuations of vegetative functions such as blood pressure and arousal. More frequent infradian oscillations of neurotransmitter and nitric oxide release fates are implicated in mutual interneural control.

Neurotransmitters and nitric oxide are released in various brain areas according to ultradian and infradian rhythms

Neurotransmitters and nitric oxide are released in various brain areas according to ultradian and infradian rhythms

Prolonged functional cerebral asymmetry as a consequence of dysfunctional parvocellular paraventricular hypothalamic nucleus signaling: An integrative model for the pathophysiology of bipolar disorder

Approximately 45 million people worldwide are diagnosed with bipolar disorder (BD). While there are many known risk factors and models of the pathologic processes influencing BD, the exact neurologic underpinnings of BD are unknown. We attempt to integrate the existing literature and create a unifying hypothesis regarding the pathophysiology of BD with the hope that a concrete model may potentially facilitate more specific diagnosis, prevention, and treatment of BD in the future. We hypothesize that dysfunctional signaling from the parvocellular neurons of the paraventricular hypothalamic nucleus (PVN) results in the clinical presentation of BD. Functional damage to this nucleus and its signaling pathways may be mediated by myriad factors (e.g. immune dysregulation and auto-immune processes, polygenetic variation, dysfunctional interhemispheric connections, and impaired or overactivated hypothalamic axes) which could help explain the wide variety of clinical presentations along the BD spectrum. The neurons of the PVN regulate ultradian rhythms, which are observed in cyclic variations in healthy individuals, and mediate changes in functional hemispheric lateralization. Theoretically, dysfunctional PVN signaling results in prolonged functional hemispheric dominance. In this model, prolonged right hemispheric dominance leads to depressive symptoms, whereas left hemispheric dominance correlated to the clinical picture of mania. Subsequently, physiologic processes that increase signaling through the PVN (hypothalamic-pituitaryadrenal axis, hypothalamic- pituitary-gonadal axis, and hypothalamic-pituitary-thyroid axis activity, suprachiasmatic nucleus pathways) as well as, neuro-endocrine induced excito-toxicity, auto-immune and inflammatory flairs may induce mood episodes in susceptible individuals. Potentially, ultradian rhythms slowing with age, in combination with changes in hypothalamic axes and maturation of neural circuitry, accounts for BD clinically presenting more frequently in young adulthood than later in life.

Ultradian rhythms in heart rate variability and distal body temperature anticipate onset of\xa0the luteinizing hormone surge

The menstrual cycle is characterized by predictable patterns of physiological change across timescales. Although patterns of reproductive hormones across the menstrual cycle, particularly ultradian rhythms, are well described, monitoring these measures repeatedly to predict the preovulatory luteinizing hormone (LH) surge is not practical. In the present study, we explored whether non-invasive measures coupled to the reproductive system: high frequency distal body temperature (DBT), sleeping heart rate (HR), sleeping heart rate variability (HRV), and sleep timing, could be used to anticipate the preovulatory LH surge in women. To test this possibility, we used signal processing to examine these measures in 45 premenopausal and 10 perimenopausal cycles alongside dates of supra-surge threshold LH and menstruation. Additionally, urinary estradiol and progesterone metabolites were measured daily surrounding the LH surge in 20 cycles. Wavelet analysis revealed a consistent pattern of DBT and HRV ultradian rhythm (2–5 h) power that uniquely enabled anticipation of the LH surge at least 2 days prior to its onset in 100% of individuals. Together, the present findings reveal fluctuations in distal body temperature and heart rate variability that consistently anticipate the LH surge, suggesting that automated ultradian rhythm monitoring may provide a novel and convenient method for non-invasive fertility assessment.

Budgerigars have complex sleep structure similar to that of mammals.

Birds and mammals share specialized forms of sleep including slow wave sleep (SWS) and rapid eye movement sleep (REM), raising the question of why and how specialized sleep evolved. Extensive prior studies concluded that avian sleep lacked many features characteristic of mammalian sleep, and therefore that specialized sleep must have evolved independently in birds and mammals. This has been challenged by evidence of more complex sleep in multiple songbird species. To extend this analysis beyond songbirds, we examined a species of parrot, the sister taxon to songbirds. We implanted adult budgerigars (Melopsittacus undulatus) with electroencephalogram (EEG) and electrooculogram (EOG) electrodes to evaluate sleep architecture, and video monitored birds during sleep. Sleep was scored with manual and automated techniques, including automated detection of slow waves and eye movements. This can help define a new standard for how to score sleep in birds. Budgerigars exhibited consolidated sleep, a pattern also observed in songbirds, and many mammalian species, including humans. We found that REM constituted 26.5% of total sleep, comparable to humans and an order of magnitude greater than previously reported. Although we observed no spindles, we found a clear state of intermediate sleep (IS) similar to non-REM (NREM) stage 2. Across the night, SWS decreased and REM increased, as observed in mammals and songbirds. Slow wave activity (SWA) fluctuated with a 29-min ultradian rhythm, indicating a tendency to move systematically through sleep states as observed in other species with consolidated sleep. These results are at variance with numerous older sleep studies, including for budgerigars. Here, we demonstrated that lighting conditions used in the prior budgerigar study-and commonly used in older bird studies-dramatically disrupted budgerigar sleep structure, explaining the prior results. Thus, it is likely that more complex sleep has been overlooked in a broad range of bird species. The similarities in sleep architecture observed in mammals, songbirds, and now budgerigars, alongside recent work in reptiles and basal birds, provide support for the hypothesis that a common amniote ancestor possessed the precursors that gave rise to REM and SWS at one or more loci in the parallel evolution of sleep in higher vertebrates. We discuss this hypothesis in terms of the common plan of forebrain organization shared by reptiles, birds, and mammals.

Environmental conditions alter behavioural organization and rhythmicity of a large Arctic ruminant across the annual cycle.

The existence and persistence of rhythmicity in animal activity during phases of environmental change is of interest in ecology, evolution and chronobiology. A wide diversity of biological rhythms in response to exogenous conditions and internal stimuli have been uncovered, especially for polar vertebrates. However, empirical data supporting circadian organization in behaviour of large ruminating herbivores remains inconclusive. Using year-round tracking data of the largest Arctic ruminant, the muskox (Ovibos moschatus), we modelled rhythmicity as a function of behaviour and environmental conditions. Behavioural states were classified based on patterns in hourly movements, and incorporated within a periodicity analyses framework. Although circadian rhythmicity in muskox behaviour was detected throughout the year, ultradian rhythmicity was most prevalent, especially when muskoxen were foraging and resting in mid-winter (continuous darkness). However, when combining circadian and ultradian rhythmicity together, the probability of behavioural rhythmicity declined with increasing photoperiod until largely disrupted in mid-summer (continuous light). Individuals that remained behaviourally rhythmic during mid-summer foraged in areas with lower plant productivity (NDVI) than individuals with arrhythmic behaviour. Based on our study, we conclude that muskoxen may use an interval timer to schedule their behavioural cycles when forage resources are low, but that the importance and duration of this timer are reduced once environmental conditions allow energetic reserves to be replenished ad libitum. We argue that alimentary function and metabolic requirements are critical determinants of biological rhythmicity in muskoxen, which probably applies to ruminating herbivores in general.

Effect of Surgical Removal of Testicles and Adrenal Glands on Ultradian Rhythms of Body Temperature in Male Wistar Rats under Conditions of Constant Illumination.

We have studied body temperature dynamics of mature male Wistar rats maintained under constant illumination after surgical removal of the testicles and adrenal glands. In gonadectomized animals, pronounced increases in body temperature (>0.9°C) were observed every 4-6 h; during the periods 03.35-04.30, 07.35-08.30, 11.35-12.30, 15.35-16.30, 19.35-20.30, and 23.35-00.30, they were recorded 1.5-fold more often than during the rest periods. These results do not significantly differ from the parameters of the control group. Combined removal of the testicles and adrenal glands led to shortening of main period of temperature oscillations to 4-4.5 h and a decrease in its amplitude; pronounced increase in body temperature (>0.5°C) was observed 2.1 times more often during the periods 03.35-04.30, 07.35-08.30, 11.35-12.30, 15.35-16.30, 19.35-20.30, and 23.35-00.30 than in other time intervals. Thus, the removal of the testicles and adrenal glands does not violate the 4-h intraday rhythm of body temperature.

Does damage to hypothalamic paraventricular nucleus underlie symptoms of ultradian rhythm disorder and an increased anxiety in coronavirus disease 2019?

Does damage to hypothalamic paraventricular nucleus underlie symptoms of ultradian rhythm disorder and an increased anxiety in coronavirus disease 2019?

Neonatal irritable sleep-wake rhythm as a predictor of autism spectrum disorders

Recently, it has been suggested that sleep problems in autism spectrum disorder (ASD) not only are associated symptoms, but may be deeply related to ASD pathogenesis. Common clinical practice relating to developmental disorders, has shown that parents of children with ASD have often stated that it is more difficult to raise children in the neonatal period because these children exhibit sleep problems. This study investigated the possibility that abnormal neonatal sleep-wake rhythms are related to future ASD development.We administered questionnaires to assess parent(s) of children with ASD and controls. A retrospective analysis was conducted among 121 children with ASD (94 male and 27 female children) recruited from the K-Development Support Center for Children (K-ASD), 56 children with ASD (40 male and 16 female children) recruited from the H-Children's Sleep and Development Medical Research Center (H-ASD) and 203 children (104 male and 99 female children) recruited from four nursery schools in T-city (control).Irritable/over-reactive types of sleep-wake rhythms that cause difficulty in raising children, such as 1) frequently waking up, 2) difficulty falling asleep, 3) short sleep hours, and 4) continuous crying and grumpiness, were observed more often in ASD groups than in the control group. Additionally, the number of the mothers who went to bed after midnight during pregnancy was higher in the ASD groups than in the control group.Sleep-wake rhythm abnormalities in neonates may be considerable precursors to future development of ASD. Formation of ultradian and postnatal circadian rhythms should be given more attention when considering ASD development. Although this is a retrospective study, the results suggest that a prospective study regarding this issue may be important in understanding and discovering intervention areas that may contribute to preventing and/or properly treating ASD.

Cell-Cell Interaction Disorders Associated with Senescence Can Be Repaired

This minireview summarizes the data concerning the possibility of compensating for one of the senescence disorders. In hepatocyte cultures of old rats, compared to young ones, the ultradian protein synthesis rhythms were reduced in amplitudes. Like other ultradian rhythms detected in vitro, protein synthesis rhythm is a marker of cell population synchronization through direct intercellular interactions. Amplitudes of the rhythm characterize the intensity of interactions. The interactions were enhanced after adding previously identified signaling factors of cell-cell communication to the culture medium: gangliosides, phenylephrine, melatonin, glutamic acid, and some regulatory peptides. The final three factors were also introduced in vivo. The effect lasted for 2–3 days. The addition of the blood serum of young rats to the culture medium increased the amplitudes of protein synthesis rhythm as well. The blood serum of old rats did not change the rhythm amplitudes. However, the blood serum of old rats enriched with gangliosides enhanced the amplitudes as effective as a young rat serum. These data, as well as some literature data, allow for recommending the use of signaling factors of cell-cell communication for improving the condition of elderly people.

A new model for the HPA axis explains dysregulation of stress hormones on the timescale of weeks.

Stress activates a complex network of hormones known as the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis is dysregulated in chronic stress and psychiatric disorders, but the origin of this dysregulation is unclear and cannot be explained by current HPA models. To address this, we developed a mathematical model for the HPA axis that incorporates changes in the total functional mass of the HPA hormone‐secreting glands. The mass changes are caused by HPA hormones which act as growth factors for the glands in the axis. We find that the HPA axis shows the property of dynamical compensation, where gland masses adjust over weeks to buffer variation in physiological parameters. These mass changes explain the experimental findings on dysregulation of cortisol and ACTH dynamics in alcoholism, anorexia, and postpartum. Dysregulation occurs for a wide range of parameters and is exacerbated by impaired glucocorticoid receptor (GR) feedback, providing an explanation for the implication of GR in mood disorders. These findings suggest that gland‐mass dynamics may play an important role in the pathophysiology of stress‐related disorders.

Ultradian Biorhythms of C57BL/6 Mice Body Temperature under Constant Illumination or during Natural Day-Night Cycle.

The study analyzed the dynamics of intraperitoneal body temperature in C57BL/6 mice during 39 days of uninterrupted measurements. When mice were exposed to constant illumination, the ultradian oscillations of body temperature demonstrated the rhythms with periods of 2 h, 60 min, and 12 min, which were the higher harmonics of the circadian temperature oscillations. In two mutually isolated groups exposed to constant illumination, the phases of revealed biorhythms coincided. When the mice maintained under natural illumination, the body temperature demonstrated the ultradian rhythms with the same periods, which indicated that constant illumination did not distort the parameters of ultradian biorhythms. Probably, there is an external biotropic factor with similar harmonic spectrum, which synchronizes these biorhythms.