Circadian rhythm of cortisol and estradiol in healthy women

ABSTRACT CIRCADIAN RHYTHM OF CORTISOL AND ESTRADIOL IN HEALTHY WOMEN by KARYN G. BUTLER AUGUST 2011 Advisor: Dr. Jean E. Davis Major: Nursing Degree: Doctor of Philosophy Daily variation in human processes and behaviors has been identified for centuries. Study of these circadian rhythms demonstrates their role in human health. Sickness behaviors include alterations in affect, sleep quality and energy. The study of the relationship between circadian rhythms has been limited to isolated rhythms. The role of temporal relationships among rhythms has received little attention. Sickness behaviors are prevalent in many disorders including depression, cancer, and autoimmune disorders. Two hormones that have been shown to play a role in the manifestation of sickness behaviors are cortisol and estradiol. To date the role of the relationship between cortisol and estradiol circadian rhythms and sickness behaviors remains unknown. The purpose of this study is to explore the temporal relationship between the rhythms of cortisol and estradiol and its relationship to sickness behaviors. It was hypothesized that a cortisol-estradiol phase angle difference (PAD) would exist that would correlate with optimal affect, sleep quality and energy. A small scale, comparative, correlational design was used to test the hypothesis. A sample of twenty-three university women (11 morning-types and 12 evening-types) between the ages of twenty to thirty-five were recruited from an urban university. Salivary samples were collected every two hours for a twenty-four hour period. Subjective measures of affect, sleep quality and energy were recorded. Salivary samples were assayed for cortisol and estradiol levels and fitted to a cosinor model with ultradian harmonics for each participant. Relationships between the cortisol-estradiol PAD and affect, sleep quality and energy measures were evaluated using a second degree polynomial equation. Results showed a significant correlation in affect measures (p \u3c 0.05), but not sleep quality or energy. An optimal PAD was identified for affect at 3.6 hours. The phase relationship between cortisol and estradiol may play a role in the development of alterations in affect which manifest in many disorders. These findings are based on a small homogeneous sample of university women. More research is needed in a larger, more heterogeneous group of women

A computational study of sleep and the hemispheres of the brain

Sleep and sleep cycles have been studied for over a century, and scientists have worked on modeling sleep for nearly as long as computers have existed. Despite this extensive study, sleep still holds many mysteries. Larger and more extensive sleep-wake models have been developed, and the circadian drive has been depicted in numerous fashions, as well as incorporated into scores of studies. With the ever-growing knowledge of sleep comes the need to find more ways to examine, quantify, and define it in the context of the most complex part of the human anatomy -- the brain. Presented here is the development of a computational model that explores the activity of individual neurons, modeled with coupled nonlinear ordinary differential equations, in key sleep-related brain regions. The activity patterns of the individual neurons are studied, as well as their synchronization with other neurons within the same region. The model is expanded into two separate interacting hemispheres, whose activity and synchronization reveal chimera-like activity. Multiple different perspectives on jetlag are presented, exploring the impact of circadian rhythm changes. Unihemispheric sleep, the unusual form of sleep exhibited by some ocean creatures and species of birds, is observed, as well as asymmetric sleep, which occurs in human subjects suffering from sleep apnea. These investigations provide a new perspective on the intricate balance between the neural activity in different brain regions that drives the essential phenomenon that is sleep --Abstract, page iii

A Computational Study of Sleep and the Hemispheres of the Brain

Sleep and sleep cycles have been studied for over a century, and scientists have worked on modeling sleep for nearly as long as computers have existed. Despite this extensive study, sleep still holds many mysteries. Larger and more extensive sleep-wake models have been developed, and the circadian drive has been depicted in numerous fashions, as well as incorporated into scores of studies. With the ever-growing knowledge of sleep comes the need to find more ways to examine, quantify, and define it in the context of the most complex part of the human anatomy – the brain. Presented here is the development of a computational model that explores the activity of individual neurons, modeled with coupled nonlinear ordinary differential equations, in key sleep-related brain regions. The activity patterns of the individual neurons are studied, as well as their synchronization with other neurons within the same region. The model is expanded into two separate interacting hemispheres, whose activity and synchronization reveal chimera-like activity. Multiple different perspectives on jetlag are presented, exploring the impact of circadian rhythm changes. Unihemispheric sleep, the unusual form of sleep exhibited by some ocean creatures and species of birds, is observed, as well as asymmetric sleep, which occurs in human subjects suffering from sleep apnea. These investigations provide a new perspective on the intricate balance between the neural activity in different brain regions that drives the essential phenomenon that is sleep

Cirkadiánní systém a spánek u jedinců s ADHD

Porucha pozornosti s hyperaktivitou (ADHD) je spojována s poruchami spánku a abnormalitami cirkadiánního systému. Studie z posledních let poukazují na souvislosti s pozdním chronotypem a syndromem opožděné spánkové fáze, polymorfismy hodinových genů, geografickou variabilitou v intenzitě slunečního záření, delší spánkovou latencí a narušenou kvalitou spánku. Výzkumy prováděné s dětskými a dospělými pacienty se však mnohdy neshodují ve svých závěrech. Přestože byla navržena nová diagnostická kategorie ADHD-SOM označující jedince, u kterých je část symptomů způsobena chronickými spánkovými potížemi, většina důkazů je korelační povahy. Práce shrnuje výzkumná zjištění týkající se cirkadiánních a spánkových korelátů ADHD a některé potenciální mechanismy, kterými by tyto koreláty mohly být s poruchou spojeny. Chronoterapie a spánkové intervence představují slibné metody v podpůrné léčbě ADHD.Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with sleep disorders and abnormalities of the circadian system. In recent studies, ADHD has been linked to late chronotype and delayed sleep phase disorder, clock gene polymorphisms, geographic variation in solar irradiation, longer sleep latency, and impaired sleep quality. However, research findings in children with ADHD often differ from those in adult patients. A new diagnostic category, ADHD-SOM, has been proposed to describe individuals whose symptoms are partially caused by chronic sleep issues. However, most of the evidence is correlational. The thesis summarizes research on sleep and circadian correlates of ADHD and some of the potential mechanisms explaining these associations. Chronotherapy and sleep interventions are promising methods of adjunctive ADHD treatment.Department of PhysiologyKatedra fyziologiePřírodovědecká fakultaFaculty of Scienc

Advances in Clinical Neurophysiology

Including some of the newest advances in the field of neurophysiology, this book can be considered as one of the treasures that interested scientists would like to collect. It discusses many disciplines of clinical neurophysiology that are, currently, crucial in the practice as they explain methods and findings of techniques that help to improve diagnosis and to ensure better treatment. While trying to rely on evidence-based facts, this book presents some new ideas to be applied and tested in the clinical practice. Advances in Clinical Neurophysiology is important not only for the neurophysiologists but also for clinicians interested or working in wide range of specialties such as neurology, neurosurgery, intensive care units, pediatrics and so on. Generally, this book is written and designed to all those involved in, interpreting or requesting neurophysiologic tests

Isolating The Effects Of Body Mass And Energy Balance On Sleep And Metabolic Health

Obesity is associated with numerous metabolic and behavioral abnormalities, including excessive daytime sleepiness independent of sleep disorders (e.g., sleep apnea). In humans, obesity is traditionally classified by weight metrics such as body mass index (BMI); over one-third of Americans are obese based on BMI. The most common cause of obesity is chronic positive energy balance due to overconsumption of calorically-dense diets. However, it is difficult to isolate the independent effects of ‘overnutrition/positive energy balance’ and ‘excess body weight’ on metabolic and behavioral parameters since the former causes the latter. Therefore, the focus of this dissertation is to discover how diet/energy balance, independent from body weight, affect sleep/wake behavior and metabolic health using the high-fat diet (HFD)-induced obese mouse model. In Chapter 2, I introduce the Diet Switch (DS) feeding paradigm which generates two groups of mice of similar body weight by divergent energy balance. Using the DS protocol, I show that diet-induced changes to energy balance can affect sleep and wakefulness independent of actual body weight. In Chapter 3, I explore the role of a central regulator of energy balance, peroxisome proliferator-activated receptor gamma (PPARg), on HFD-induced sleep abnormalities; our results indicate that central PPARg does not influence sleep/wake behavior. In Chapter 4, I again use the DS feeding paradigm, but instead measure various molecular (blood biomarkers and hypothalamic gene expression), behavioral (spontaneous activity), and metabolic (indirect calorimetry) outcomes. Using linear regression modeling, I quantify the relative influence of body weight and diet/energy balance on these parameters, and relate these key findings to the results from Chapter 2. Taken together, these studies offer novel insights into the pathogenesis and reversibility of obesity-related sleep and metabolic disorders

Rhythmic Masticatory Muscle Activity during Sleep: Etiology and Clinical Perspectives

L’activité rythmique des muscles masticateurs (ARMM) pendant le sommeil se retrouve chez environ 60% de la population générale adulte. L'étiologie de ce mouvement n'est pas encore complètement élucidée. Il est cependant démontré que l’augmentation de la fréquence des ARMM peut avoir des conséquences négatives sur le système masticatoire. Dans ce cas, l'ARMM est considérée en tant que manifestation d'un trouble moteur du sommeil connue sous le nom de bruxisme. Selon la Classification Internationale des Troubles du Sommeil, le bruxisme est décrit comme le serrement et grincement des dents pendant le sommeil. La survenue des épisodes d’ARMM est associée à une augmentation du tonus du système nerveux sympathique, du rythme cardiaque, de la pression artérielle et elle est souvent en association avec une amplitude respiratoire accrue. Tous ces événements peuvent être décrits dans le contexte d’un micro-éveil du sommeil. Cette thèse comprend quatre articles de recherche visant à étudier i) l'étiologie de l’ARMM pendant le sommeil en relation aux micro-éveils, et à évaluer ii) les aspects cliniques du bruxisme du sommeil, du point de vue diagnostique et thérapeutique. Pour approfondir l'étiologie de l’ARMM et son association avec la fluctuation des micro-éveils, nous avons analysé le patron cyclique alternant (ou cyclic alternating pattern (CAP) en anglais), qui est une méthode d’analyse qui permet d’évaluer l'instabilité du sommeil et de décrire la puissance des micro-éveils. Le CAP a été étudié chez des sujets bruxeurs et des sujets contrôles qui ont participé à deux protocoles expérimentaux, dans lesquels la structure et la stabilité du sommeil ont été modifiées par l'administration d'un médicament (la clonidine), ou avec l'application de stimulations sensorielles (de type vibratoire/auditif) pendant le sommeil. Dans ces deux conditions expérimentales caractérisées par une instabilité accrue du sommeil, nous étions en mesure de démontrer que les micro-éveils ne sont pas la cause ou le déclencheur de l’ARMM, mais ils représentent plutôt la «fenêtre permissive» qui facilite l'apparition de ces mouvements rythmiques au cours du sommeil. Pour évaluer la pertinence clinique du bruxisme, la prévalence et les facteurs de risque, nous avons effectué une étude épidémiologique dans une population pédiatrique (7-17 ans) qui était vue en consultation en orthodontie. Nous avons constaté que le bruxisme est un trouble du sommeil très fréquent chez les enfants (avec une prévalence de 15%), et il est un facteur de risque pour l'usure des dents (risque relatif rapproché, RRR 8,8), la fatigue des muscles masticateurs (RRR 10,5), les maux de tête fréquents (RRR 4,3), la respiration bruyante pendant le sommeil (RRR 3,1), et divers symptômes liés au sommeil, tels que la somnolence diurne (RRR 7,4). Ces résultats nous ont amenés à développer une étude expérimentale pour évaluer l'efficacité d'un appareil d'avancement mandibulaire (AAM) chez un groupe d'adolescents qui présentaient à la fois du bruxisme, du ronflement et des maux de tête fréquents. L'hypothèse est que dans la pathogenèse de ces comorbidités, il y a un mécanisme commun, probablement lié à la respiration pendant le sommeil, et que l'utilisation d'un AAM peut donc agir sur plusieurs aspects liés. À court terme, le traitement avec un AAM semble diminuer l'ARMM (jusqu'à 60% de diminution), et améliorer le ronflement et les maux de tête chez les adolescents. Cependant, le mécanisme d'action exact des AAM demeure incertain; leur efficacité peut être liée à l'amélioration de la respiration pendant le sommeil, mais aussi à l'influence que ces appareils pourraient avoir sur le système masticatoire. Les interactions entre le bruxisme du sommeil, la respiration et les maux de tête, ainsi que l'efficacité et la sécurité à long terme des AAM chez les adolescents, nécessitent des études plus approfondies.Approximately 60% of the general adult population experiences rhythmic masticatory muscle activity (RMMA) during sleep. The etiology of this movement is not yet understood. However, it has been demonstrated that an increased frequency of RMMA may have detrimental consequences on the stomatognathic system. In this case, RMMA is considered the manifestation of a sleep-related motor disorder known as sleep bruxism (SB). According to the definition of the International Classification of Sleep Disorders, SB is the activity of tooth grinding and clenching during sleep. The occurrence of SB-related activity, i.e., RMMA, is associated with rises of sympathetic tone, heart rate, blood pressure, and it is frequently concomitant with larger respiratory breaths. All these events can be described within a sleep arousal. The present thesis includes four research articles aimed to study i) the etiology of RMMA during sleep in relation to sleep arousal; and ii) the clinical perspectives of SB assessment and management. To further investigate the etiology of RMMA and its association with sleep arousal fluctuations we analyzed the cyclic alternating pattern (CAP), a scoring method to assess sleep instability and describe sleep arousal pressure. CAP was scored in SB subjects and controls that participated in two experimental protocols in which sleep architecture and stability were altered by either a medication (i.e., clonidine), or sensory stimulations (i.e., vibratory/auditory). Under these experimental conditions known to increase sleep instability, we were able to show that sleep arousal is not the trigger or cause of RMMA, rather the “permissive window” that facilitates the occurrence of RMMA during sleep. To evaluate the clinical relevance of SB, we conducted a survey on a 7-17 year old orthodontic population to investigate the prevalence and risk factors associated with SB. It appeared that SB is a highly prevalent sleep disorders in children (15% of prevalence), and is a risk factor for tooth wear (odds ratio, OR 8.8), jaw muscle fatigue (OR 10.5), frequent headache (OR 4.3), loud breathing during sleep (OR 3.1), and several sleep complaints, such as daytime sleepiness (OR 7.4). These findings led us to design an experimental trial using a mandibular advancement appliance (MAA) in adolescents in order to investigate the possible relationship between SB, snoring, and headache. We hypothesized that a common underlying mechanism related to breathing during sleep may be responsible for all concomitant conditions. The short-term use of an MAA appeared to reduce SB (up to 60%), and improve snoring and headache complaints in adolescents. However, the precise mechanism of action of MAA remains under debate; its effectiveness can be either related to the improvement of breathing during sleep, or its influence on the masticatory system. The interactions between SB, breathing, and headache as well as the long-term effectiveness and safety of the MAA in adolescents need further investigations.L’attività ritmica dei muscoli masticatori (ARMM) durante il sonno si osserva in circa il 60% della popolazione generale adulta. L'eziologia di questo movimento non è stata ancora del tutto compresa. Tuttavia, è dimostrato che un’aumentata frequenza di ARMM può avere conseguenze negative sul sistema stomatognatico. In questo caso, l’ARMM è considerato la manifestazione di un disturbo motorio del sonno noto come bruxismo. Secondo la Classificazione Internazionale dei Disturbi del Sonno, il bruxismo è l'attività di digrignamento e serramento dei denti durante il sonno. La comparsa di episodi di ARMM durante il sonno è associata a un aumento del tono del sistema nervoso simpatico, della frequenza cardiaca, della pressione arteriosa, ed è spesso in concomitanza con un aumentato volume inspiratorio. Le variazioni di questi parametri fisiologici sono compresi nel contesto di un arousal (micro risveglio) del sonno. Questa tesi comprende quattro articoli di ricerca volti a studiare i) l'eziologia dell’ARMM durante il sonno in relazione all’arousal, ed a valutare ii) l’inquadramento clinico del bruxismo nel sonno. Per approfondire l'eziologia dell’ARMM e l’associazione con l’arousal nel sonno, abbiamo analizzato il cyclic alternating pattern (CAP), che permette di valutare l'instabilità del sonno e descrivere la potenza degli arousals. Il CAP è stato esaminato in soggetti con bruxismo e soggetti controllo che hanno partecipato in due protocolli sperimentali, in cui la struttura e la stabilità del sonno sono stati modificati con la somministrazione di un farmaco (la clonidina), o con l’applicazione di stimolazioni sensoriali (di tipo vibratorio/uditivo) durante il sonno. In queste condizioni sperimentali caratterizzate da un’aumentata instabilità del sonno, siamo stati in grado di dimostrare che l’arousal non è la causa o il generatore dell’ARMM, ma piuttosto la "finestra permissiva" che facilita il verificarsi di questi movimenti ritmici durante il sonno. Per valutare la rilevanza clinica del bruxismo, abbiamo condotto uno studio epidemiologico in una popolazione pediatrica afferente alla clinica di ortodonzia per studiare la prevalenza e i fattori di rischio associati al bruxismo. Questa ricerca ha evidenziato che il bruxismo è un comune disturbo del sonno nei bambini (con una prevalenza del 15%), ed è un fattore di rischio per usura dentale (odds ratio, OR 8.8), fatica dei muscoli masticatori (OR 10.5), mal di testa frequenti (OR 4.3), respirazione rumorosa durante il sonno (OR 3.1), e diversi sintomi legati al sonno, quali la sonnolenza diurna (OR 7.4). Questi risultati ci hanno portato a progettare uno studio sperimentale per valutare l’efficacia di un apparecchio di avanzamento mandibolare (AAM) in un gruppo di adolescenti che presentavano al contempo bruxismo, russamento e frequenti cefalee. L’ipotesi è che nella patogenesi di tali comorbidità, vi sia un meccanismo comune, probabilmente legato alla respirazione durante il sonno, e che l’utilizzo di un AAM possa quindi avere un beneficio multiplo. Il trattamento a breve termine con un AAM sembra diminuire l’ARMM (fino al 60%) e migliorare il russamento e i mal di testa negli adolescenti. Tuttavia, l'esatto meccanismo di azione degli AAM rimane incerto; la loro efficacia può essere correlata sia al miglioramento della respirazione durante il sonno, ma anche all’influenza che questi apparecchi svolgono sul sistema masticatorio. Le interazioni tra il bruxismo nel sonno, la respirazione, e le cefalee, così come l'efficacia e la sicurezza a lungo termine degli AAM negli adolescenti, necessitano di ulteriori studi clinici

Parameters Characterization and Cognitive-Behavioral Effects of Transcranial Pulsed Current Stimulation

Neuromodulation is being recognized as “technology impacting on the neural interface” And noninvasive brain stimulation (NIBS) is becoming an interesting alternative for this interface. Transcranial pulsed current stimulation (tPCS) is emerging as an option in the field of neuromodulation as a technique that employs weak, pulsed current at different frequency ranges, inducing electrical fields that reach cortical and subcortical structures; however, little is known about its properties and mechanistic effects on electrical brain activity and how it can modulate its oscillatory patterns. Moreover, there is not clear understanding in how tPCS can affect cognition and behavior or its neurophysiological correlates as indexed by autonomic responses. This research looked at the mechanisms behind tPCS in four randomized clinical trials; the main aim of each experiment was to evaluate the effects of tPCS in quantitative electroencephalography (qEEG) and cognitive-behavioral testing by exploring different parameters of stimulation. Based in the findings obtained per experiment, tPCS can be defined as a safe and tolerable technique that modulates the power spectrum of qEEG signals by means of applied randomized frequencies in a pre-defined range, tPCS also facilitates connectivity in the area of influence by the electrical field and this has an impact on optimization of performance by decreasing reaction times (RT) in attention switching task and by facilitating wide-ranging network processing as in the case of arithmetic functioning. This work also delivered an insight about the potential that tPCS has for future clinical applications.The Labuschagne-Foundation Spaulding Neurmodulation Cente

Big data analysis of cyclic alternating pattern during sleep using deep learning

Sleep scoring has been of great interest since the invention of the polysomnography method, which enabled the recording of physiological signals overnight. With the surge in wearable devices in recent years, the topic of what is high-quality sleep, how can it be determined and how can it be achieved attracted increasing interest. In the last two decades, cyclic alternating pattern (CAP) was introduced as a scoring alternative to traditional sleep staging. CAP is known as a synonym for sleep microstructure and describes sleep instability. Manual CAP scoring performed by sleep experts is a very exhausting and time-consuming task. Hence, an automatic method would facilitate the processing of sleep data and provide a valuable tool to enhance the understanding of the role of CAP. This thesis aims to expand the knowledge about CAP by developing a high-performance automated CAP scoring system that can reliably detect and classify CAP events in sleep recordings. The automated system is equipped with state-of-the-art signal processing methods and exploits the dynamic, temporal information in brain activity using deep learning. The automated scoring system is validated using large community-based cohort studies and comparing the output to verified values in the literature. Our findings present novel clinical results on the relationship between CAP and age, gender, subjective sleep quality, and sleep disorders demonstrating that automated CAP analysis of large population based studies can lead to new findings on CAP and its subcomponents. Next, we study the relationship between CAP and behavioural, cognitive, and quality-of-life measures and the effect of adenotonsillectomy on CAP in children with obstructive sleep apnoea as the link between CAP and cognitive functioning in children is largely unknown. Finally, we investigate cortical-cardiovascular interactions during CAP to gain novel insights into the causal relationships between cortical and cardiovascular activity that are underpinning the microstructure of sleep. In summary, the research outcomes in this thesis outline the importance of a fully automated end-to-end CAP scoring solution for future studies on sleep microstructure. Furthermore, we present novel critical information for a better understanding of CAP and obtain first evidence on physiological network dynamics between the central nervous system and the cardiovascular system during CAP.Thesis (Ph.D.) -- University of Adelaide, School of Electrical and Electronic Engineering, 202