1,663 research outputs found

    SEMIAUTOMATIC ANALYSIS OF SLEEP MICROSTRUCTURE PARAMETERS: AROUSAL, CYCLIC ALTERNATING PATTERN AND REM MUSCLE ATONIA.

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    This thesis project is focused on systems of automatic analysis of sleep parameters and it is composed by two main parts: the first is focused on the process of creation of a software for the analysis of Cyclic Alternating Pattern (CAP) a particular parameter of sleep microstructure and the second part is focused on the use of automatic analysis of muscle activity during sleep. CAP is defined as periodic EEG activity of NREM sleep characterized by sequences of transient electrocortical events, that are distinct from the background electroencephalogram (EEG) activity and occurs at up to 1-minute intervals. CAP represents the microstructure of sleep, and its analysis gives fundamental information that are otherwise neglected with the analysis of sleep macrostructure (sleep staging) alone. CAP is considered a marker for the evaluation of sleep stability and its oscillatory presence is fundamental preservation of sleep stability through the night and in response to arousal stimuli. Analysis of CAP is a very time consuming procedure and it is still used mainly for research purpose rather than in the clinical practice. The development of a software for the analysis of CAP was the main focus of the work in collaboration with MicromedÂź (an international company for the manufacturing of hardware and software for neurophysiology based in Mogliano Veneto (TV)). During the months spent at MicromedÂź the PhD student worked with the software programmers and engineers for the creation and validation of the software, individuating all the clinical parameters from guidelines and verifying their correct application and the validity of the results. In the first part of this thesis all the creation process is described in detail. The second part of this thesis is focused on the automatic analysis of muscle EMG tone during both REM and NREM sleep. Muscle tone during sleep gradually diminishes throughout the different sleep stages reaching its minimum with REM muscle atonia. Evaluation of muscle tone during REM sleep is fundamental for the diagnosis of REM sleep Behavior Disorder (RBD) in which there is loss of muscle atonia during REM associated to dream enacting behavior. Muscle activity is measured in polysomnography (PSG) through the recording of different EMG channels. This activity is evaluated almost exclusively during REM sleep using a manual method of visual scoring that require high expertise is highly time consuming. A validated method developed by R. Ferri and co. allows automatic analysis of chin EMG activity through the calculation of Atonia index. Few studies evaluated muscle tone during NREM sleep, and little is known about the neurophysiology of muscle control. Manual methods would be difficult to apply to NREM sleep; the method developed by Ferri is capable to perform an analysis of muscle tone for all sleep stages. RBD is associated to neurodegenerative disorders, synucleinopathies such as Parkinson disease (PD), Multiple System Atrophy (MSA). MSA patients have a more severe loss of atonia during REM sleep compared to PD with RBD. Starting from the fortuitous observation of a prominent facial activity during NREM sleep, we decided to evaluate the facial activity recorded in vPSG in patients with PD, MSA and controls and to evaluate the muscle tone in both REM and NREM sleep using the automatic method for the calculation of atonia index. Our results showed that MSA have a more sustained muscle tone compared to healthy controls in all sleep stages and compared to PD in all NREM stages. Moreover a particular facial expression was noted to be significantly more frequent in MSA compared to PD. This results may help the differential diagnosis between PD and MSA. This is the first study to evaluate muscle tone during all sleep stages using Atonia index and this analysis may open to different perspectives for the understanding of REM behavior disorder and the mechanism underlying the control of muscle tone in NREM slee

    Disorders of Arousal in adults: new diagnostic tools for clinical practice

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    Abstract Disorders of Arousal (DOA) are mental and motor behaviors arising from NREM sleep. They comprise a spectrum of manifestations of increasing intensity from confusional arousals to sleep terrors to sleepwalking. Although DOA in childhood are usually harmless, in adulthood they are often associated with injurious or violent behaviors to the patient or others. Driving motor vehicles, suspected suicide, and even homicide or attempted homicide have been described during sleepwalking in adults. Furthermore, adult DOA need to be differentiated from other sleep disorders such as Sleep-related Hypermotor Epilepsy or REM Sleep Behavior Disorder. Although many aspects of DOA have been clarified in the last two decades there is still a lack of objective and quantitative diagnostic criteria for DOA. Recent advances in EEG analysis and in the semiological characterization of DOA motor patterns have provided a better definition of DOA diagnosis. Our article focuses on the DOA diagnostic process describing accurately the newest DOA clinical, EEG and video-polysomnographic tools in order to aid clinicians in DOA assessment

    Analisi dei parametri di risposta cerebrale e vegetativa agli eventi respiratori nel sonno in pazienti affetti da sindrome delle apnee morfeiche

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    The arousal scoring in Obstructive Sleep Apnea Syndrome (OSAS) is important to clarify the impact of the disease on sleep but the currently applied American Academy of Sleep Medicine (AASM) definition may underestimate the subtle alterations of sleep. The aims of the present study were to evaluate the impact of respiratory events on cortical and autonomic arousal response and to quantify the additional value of cyclic alternating pattern (CAP) and pulse wave amplitude (PWA) for a more accurate detection of respiratory events and sleep alterations in OSAS patients. A retrospective revision of 19 polysomnographic recordings of OSAS patients was carried out. Analysis was focused on quantification of apneas (AP), hypopneas (H) and flow limitation (FL) events, and on investigation of cerebral and autonomic activity. Only 41.1% of FL events analyzed in non rapid eye movement met the AASM rules for the definition of respiratory event-related arousal (RERA), while 75.5% of FL events ended with a CAP A phase. The dual response (EEG-PWA) was the most frequent response for all subtypes of respiratory event with a progressive reduction from AP to H and FL. 87.7% of respiratory events with EEG activation showed also a PWA drop and 53,4% of the respiratory events without EEG activation presented a PWA drop. The relationship between the respiratory events and the arousal response is more complex than that suggested by the international classification. In the estimation of the response to respiratory events, the CAP scoring and PWA analysis can offer more extensive information compared to the AASM rules. Our data confirm also that the application of PWA scoring improves the detection of respiratory events and could reduce the underestimation of OSAS severity compared to AASM arousal

    Intensity of respiratory cortical arousals is a distinct pathophysiologic feature and is associated with disease severity in obstructive sleep apnea patients

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    Background: We investigated whether the number, duration and intensity of respiratory arousals (RA) on C3-electroencephalographic (EEG) recordings correlate with polysomnography (PSG)-related disease severity in obstructive sleep apnea (OSA) patients. We also investigated if every patient might have an individual RA microstructure pattern, independent from OSA-severity. Methods: PSG recordings of 20 OSA patients (9 female; age 27–80 years) were analyzed retrospectively. Correlation coefficients were calculated between RA microstructure (duration, EEG-intensity) and RA number and respiratory disturbance index (RDI), oxygen desaturation index (ODI) and arousal index (AI). Intraclass correlations (ICC) for both RA duration and intensity were calculated. Sleep stage-specific and apnea- and hypopnea-specific analyses were also done. The probability distributions of duration and intensity were plotted, interpolated with a kernel which fits the distribution. A Bayesian posterior distribution analysis and pair-wise comparisons of each patient with all other 19 patients were performed. Results: Of the analyzed 2600 RA, strong positive correlations were found between average RA intensity and both RDI and AI. The number of PSG-recorded RA was strongly positively correlated with RDI. Significant correlations between average RA intensity in REM, NREM2 and NREM3 sleep stages and total ODI were identified. No sleep stage-specific correlations of arousal microstructure with age, sex, RDI or AI were identified. Although between-subjects ICC values were 0.7 (all p < 0.05). While apnea-related RA duration did not differ from hypopnea-related RA duration, RA intensity was significantly higher (p = 0.00135) in hypopneas than in apneas. A clear individual pattern of arousal duration for each patient was made distinct. For arousal intensity, a Gaussian distribution was identified in most patients. The Bayesian statistics regarding the arousal microstructure showed significant differences between each pair of patients. Conclusions: Each individual patient with OSA might have an individual pattern of RA intensity and duration indicating a distinct individual pathophysiological feature. Arousal intensity was significantly higher in hypopneic than in apneic events and may be related causally to the diminished (compared to apneas) respiratory distress associated with hypopneas. RA intensity in REM, NREM2 and NREM3 strongly correlated with ODI

    Considering REM Sleep Behavior Disorder in the Management of Parkinson's Disease

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    Rapid eye movement (REM) sleep behavior disorder (RBD) is the result of the loss of physiological inhibition of muscle tone during REM sleep, characterized by dream-enacting behavior and widely recognized as a prodromal manifestation of alpha-synucleinopathies. Indeed, patients with isolated RBD (iRBD) have an extremely high estimated risk to develop a neurodegenerative disease after a long follow up. Nevertheless, in comparison with PD patients without RBD (PDnoRBD), the occurrence of RBD in the context of PD (PDRBD) seems to identify a unique, more malignant phenotype, characterized by a more severe burden of disease in terms of both motor and non-motor symptoms and increased risk for cognitive decline. However, while some medications (eg, melatonin, clonazepam, etc.) and non-pharmacological options have been found to have some therapeutic benefits on RBD there is no available treatment able to modify the disease course or, at least, slow down the neurodegenerative process underlying phenoconversion. In this scenario, the long prodromal phase may allow an early therapeutic window and, therefore, the identification of multimodal biomarkers of disease onset and progression is becoming increasingly crucial. To date, several clinical (motor, cognitive, olfactory, visual, and autonomic features) neurophysiological, neuroimaging, biological (biofluids or tissue biopsy), and genetic biomarkers have been identified and proposed, also in combination, as possible diagnostic or prognostic markers, along with a potential role for some of them as outcome measures and index of treatment response. In this review, we provide an insight into the present knowledge on both existing and future biomarkers of iRBD and highlight the difference with PDRBD and PDnoRBD, including currently available treatment options

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

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    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

    Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 217, March 1981

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    Approximately 130 reports, articles, and other documents introduced into the NASA scientific and technical information system in February 1981 are included in this bibliography. Topics include aerospace medicine and biology

    EEG functional connectivity prior to sleepwalking : evidence of interplay between sleep and wakefulness

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    Study Objectives: Although sleepwalking (somnambulism) affects up to 4% of adults, its pathophysiology remains poorly understood. Sleepwalking can be preceded by fluctuations in slow-wave sleep EEG signals, but the significance of these pre-episode changes remains unknown and methods based on EEG functional connectivity have yet to be used to better comprehend the disorder. Methods: We investigated the sleep EEG of 27 adult sleepwalkers (mean age: 29 ± 7.6 years) who experienced a somnambulistic episode during slow-wave sleep. The 20-second segment of sleep EEG immediately preceding each patient’s episode was compared with the 20-second segment occurring 2 minutes prior to episode onset. Results: Results from spectral analyses revealed increased delta and theta spectral power in the 20 seconds preceding the episodes’ onset as compared to the 20 seconds occurring 2 minutes before the episodes. The imaginary part of the coherence immediately prior to episode onset revealed (1) decreased delta EEG functional connectivity in parietal and occipital regions, (2) increased alpha connectivity over a fronto-parietal network, and (3) increased beta connectivity involving symmetric inter-hemispheric networks implicating frontotemporal, parietal and occipital areas. Conclusions: Taken together, these modifications in EEG functional connectivity suggest that somnambulistic episodes are preceded by brain processes characterized by the co-existence of arousal and deep slee

    THE MANY WAYS OF WAKING UP FROM SLEEP - MOVING FORWARD THE ANALYSIS OF SLEEP MICROARCHITECTURE

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    One of the defining characteristics of sleep is that it is readily reversible towards wakefulness. This is exemplified in the common daily experience of waking up in the morning. My thesis studies sleep-wake transitions that are equally common and frequent, yet often not consciously perceived and neglected as random sleep perturbations of minor significance. Using mice as an experimental species, I find that healthy non-rapid-eye-movement sleep (NREMS), also named deep restorative sleep, is a dynamic brain state showing defined, periodically recurring moments of fragility. During these, diverse types of brief arousal-like events with various combinations of physiological correlates appear, including global or local cortical activation, muscle activity, and heart rate changes. Using a mice model of chronic neuropathic pain, I find that the rules I have identified in healthy sleep serve to identify previously unrecognized sleep disruptions that could contribute to sleep complaints of chronic pain patients. The experimental and analytical methods I have developed in these studies also helped in the identification of the neuronal basis of the fragility periods of NREM sleep. Together, my studies offer novel insights and analytical tools for the study of sleep-wake transitions and their perturbance in pathological conditions linked to sensory discomfort. More specifically, my work departed from recent findings that NREMS in mice is divided in recurring periods of sleep fragility at frequencies ~0.02 Hz, characterized by heightened arousability. Through analyzing the temporal distribution of brief arousal events termed microarousals, I hypothesized that these fragility periods could serve a time raster for the probing of spontaneous sleep perturbations. Motivated by the question of how sensory discomfort caused by pain affects sleep, I have used the spared nerve injury (SNI) model, which consists in the injury of two of the 3 branches of the sciatic nerve. I found that the role of fragility periods in timing spontaneous arousals is highly useful to identify sleep disruptions not commonly detected with standard polysomnographic measures. Thus, by scrutinizing the fragility periods of NREMS in the SNI mice, I discovered an overrepresentation of a novel form of local perturbation within the hindlimb primary somatosensory cortex (S1HL), accompanied by heart rate increases. In addition, I showed that SNI animals woke up more frequently facing external stimuli, using closed-loop methods targeting specifically the fragility or continuity periods. These findings led me to propose that chronic pain-related sleep complaints may arise primarily from a perturbed arousability. The closed-loop techniques to probe arousability could be transferred to interrogate neuronal mechanisms underlying NREMS fragility, leading to the recognition that intrusion of wake-related activity into NREMS is a previously underappreciated mechanism controlling sleep fragility and architecture. Overall, I present my thesis to advance the view on NREMS as a dynamic heterogeneous state of which insights into its neuronal mechanisms, and its physio- and pathophysiological manifestations in animal models should be key to formulate testable hypotheses aimed to cure the suffering of sleep disorder in human. -- Une des caractĂ©ristiques qui dĂ©finit le sommeil, est que l’on peut rapidement retourner Ă  un Ă©tat d’éveil. De fait, nous l’expĂ©rimentons chaque matin au rĂ©veil. Ma thĂšse Ă©tudie les transitions sommeil-Ă©veil qui, bien que frĂ©quentes, sont souvent non consciemment perçues et traitĂ©es comme des perturbations sans importance et alĂ©atoires du sommeil. En utilisant la souris comme modĂšle expĂ©rimental, je montre que le sommeil sans mouvements rapides des yeux (NREMS), Ă©galement appelĂ© le sommeil profond et rĂ©parateur, est un Ă©tat cĂ©rĂ©bral dynamique composĂ© de pĂ©riodes discrĂštes et rĂ©currentes de fragilitĂ© face Ă  des stimuli externe. Pendant celles-ci, plusieurs types d’évĂšnements associĂ©s Ă  des Ă©veils brefs apparaissent, combinant activation corticale, activitĂ© musculaire et/ou une hausse des battements cardiaques. Je dĂ©montre que la comprĂ©hension des transitions sommeil-Ă©veil physiologiques s’avĂšre utile pour Ă©tudier le sommeil de souris souffrant de douleurs neuropathiques chroniques. Ces souris prĂ©sentent un nouveau type de perturbations locales lors du sommeil, qui pourraient possiblement expliquer une partie des plaintes de mauvais sommeil exprimĂ©es par les patients souffrant de douleurs chroniques. Les mĂ©thodes analytiques et expĂ©rimentales que j’ai dĂ©veloppĂ©es dans ces Ă©tudes ont aussi aidĂ© Ă  l’identification des bases neuronales de la genĂšse des pĂ©riodes de fragilitĂ©s du sommeil NREM. En somme, mes Ă©tudes offrent des connaissances inĂ©dites et des mĂ©thodes d’analyses pour l’étude des transitions sommeil-Ă©veil et de leurs perturbations en conditions pathologiques. Une Ă©tude rĂ©cente du laboratoire a montrĂ© que le sommeil NREM est divisĂ© en pĂ©riodes de fragilitĂ© alternant avec des pĂ©riodes de non-fragilitĂ© (continuitĂ©), environ toutes les 50 secondes ce qui donne une frĂ©quence de 0.02 Hz. Les pĂ©riodes de fragilitĂ© sont caractĂ©risĂ©es par une hausse de « l’éveillabilitĂ© » ou propension Ă  s’éveiller. Ma premiĂšre observation est que les Ă©veils brefs, couramment appelĂ©s micro-rĂ©veils, prĂ©sentent une distribution temporelle hautement restreinte aux pĂ©riodes de fragilitĂ©. Ainsi, j’ai Ă©mis l’hypothĂšse que ces pĂ©riodes pourraient servir de moments spĂ©cialement choisis par le cerveau pour la mesure de potentielles perturbations spontanĂ©es. MotivĂ© par la question de comment les douleurs chroniques perturbent le sommeil, je l’ai analysĂ© chez un modĂšle de souris de douleurs neuropathique, le modĂšle de d’épargne du nerf sural (SNI). Le rĂŽle des pĂ©riodes de fragilitĂ© Ă  restreindre les micro- rĂ©veils s’est avĂ©rĂ© trĂšs utile pour dĂ©tecter de nouvelles formes de rĂ©action Ă  des perturbations qui ne sont pas Ă©videntes par des analyses classiques du sommeil. En effet, spĂ©cifiquement pendant ces pĂ©riodes de fragilitĂ©, j’ai dĂ©couvert une sur-reprĂ©sentation d’un nouveau type d’éveil local confinĂ© au cortex somatosensoriel primaire et accompagnĂ© d’une hausse du rythme cardiaque. De plus, en utilisant de nouvelles mĂ©thodes basĂ©es sur des boucles-fermĂ©es, j’ai dĂ©montrĂ© que les souris SNI se rĂ©veillaient plus frĂ©quemment que leurs contrĂŽles en faisant face Ă  des stimuli externes. Sur la base de ces dĂ©couvertes, je propose que les plaintes de mauvais sommeil chez les patients souffrant de douleurs chroniques puissent prendre leur source dans une Ă©veillabilitĂ© perturbĂ©e. Les mĂ©thodes de boucles-fermĂ©es pour analyser l’éveillabilitĂ© a aussi pu ĂȘtre transfĂ©rĂ©e pour l’étude optogĂ©nĂ©tique des mĂ©canismes neuronaux Ă  la base de la fragilitĂ© du sommeil NREM. Cela a menĂ© Ă  la reconnaissance que l’intrusion d’activitĂ© normalement associĂ©e Ă  l’éveil dans le sommeil est un mĂ©canisme de contrĂŽle de sa fragilitĂ© et de son architecture souvent ignorĂ© dans le domaine. En somme, ma thĂšse permet une avancĂ©e de notre vision du sommeil NREM comme Ă©tant un Ă©tat dynamique et hĂ©tĂ©rogĂšne dont les mĂ©canismes neuronaux sous-jacent, en conditions normales et pathogĂ©niques, sont clefs pour la formulation d’hypothĂšses testables visant Ă  la guĂ©rison des patients souffrant de troubles du sommeil
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