Multivariate assessment of linear and non-linear causal coupling pathways within the central-autonomic-network in patients suffering from schizophrenia

Im Bereich der Zeitreihenanalyse richtet sich das Interesse zunehmend darauf, wie Einblicke in die Interaktions- und Regulationsprozesse von pathophysiologischen- und physiologischen Zuständen erlangt werden können. Neuste Fortschritte in der nichtlinearen Dynamik, der Informationstheorie und der Netzwerktheorie liefern dabei fundiertes Wissen über Kopplungswege innerhalb (patho)physiologischer (Sub)Systeme. Kopplungsanalysen zielen darauf ab, ein besseres Verständnis dafür zu erlangen, wie die verschiedenen integrierten regulatorischen (Sub)Systeme mit ihren komplexen Strukturen und Regulationsmechanismen das globale Verhalten und die unterschiedlichen physiologischen Funktionen auf der Ebene des Organismus beschreiben. Insbesondere die Erfassung und Quantifizierung der Kopplungsstärke und -richtung sind wesentliche Aspekte für ein detaillierteres Verständnis physiologischer Regulationsprozesse. Ziel dieser Arbeit war die Charakterisierung kurzfristiger unmittelbarer zentral-autonomer Kopplungspfade (top-to-bottom und bottom to top) durch die Kopplungsanalysen der Herzfrequenz, des systolischen Blutdrucks, der Atmung und zentraler Aktivität (EEG) bei schizophrenen Patienten und Gesunden. Dafür wurden in dieser Arbeit neue multivariate kausale und nicht-kausale, lineare und nicht-lineare Kopplungsanalyseverfahren (HRJSD, mHRJSD, NSTPDC) entwickelt, die in der Lage sind, die Kopplungsstärke und -richtung, sowie deterministische regulatorische Kopplungsmuster innerhalb des zentralen-autonomen Netzwerks zu quantifizieren und zu klassifizieren. Diese Kopplungsanalyseverfahren haben ihre eigenen Besonderheiten, die sie einzigartig machen, auch im Vergleich zu etablierten Kopplungsverfahren. Sie erweitern das Spektrum neuartiger Kopplungsansätze für die Biosignalanalyse und tragen auf ihre Weise zur Gewinnung detaillierter Informationen und damit zu einer verbesserten Diagnostik/Therapie bei. Die Hauptergebnisse dieser Arbeit zeigen signifikant schwächere nichtlineare zentral-kardiovaskuläre und zentral-kardiorespiratorische Kopplungswege und einen signifikant stärkeren linearen zentralen Informationsfluss in Richtung des Herzkreislaufsystems auf, sowie einen signifikant stärkeren linearen respiratorischen Informationsfluss in Richtung des zentralen Nervensystems in der Schizophrenie im Vergleich zu Gesunden. Die detaillierten Erkenntnisse darüber, wie die verschiedenen zentral-autonomen Netzwerke mit paranoider Schizophrenie assoziiert sind, können zu einem besseren Verständnis darüber führen, wie zentrale Aktivierung und autonome Reaktionen und/oder Aktivierung in physiologischen Netzwerken unter pathophysiologischen Bedingungen zusammenhängen.In the field of time series analysis, increasing interest focuses on insights gained how the coupling pathways of regulatory mechanisms work in healthy and ill states. Recent advances in non-linear dynamics, information theory and network theory lead to a new sophisticated body of knowledge about coupling pathways within (patho)physiological (sub)systems. Coupling analyses aim to provide a better understanding of how the different integrated physiological (sub)systems, with their complex structures and regulatory mechanisms, describe the global behaviour and distinct physiological functions at the organism level. In particular, the detection and quantification of the coupling strength and direction are important aspects for a more detailed understanding of physiological regulatory processes. This thesis aimed to characterize short-term instantaneous central-autonomic-network coupling pathways (top-to-bottom and bottom to top) by analysing the coupling of heart rate, systolic blood pressure, respiration and central activity (EEG) in schizophrenic patients and healthy participants. Therefore, new multivariate causal and non-causal linear and non-linear coupling approaches (HRJSD, mHRJSD, NSTPDC) that are able to determine the coupling strength and direction were developed. Whereby, the HRJSD and mHRJSD approaches allow the quantification and classification of deterministic regulatory coupling patterns within and between the cardiovascular- the cardiorespiratory system and the central-autonomic-network were developed. These coupling approaches have their own unique features, even as compared to well-established coupling approaches. They expand the spectrum of novel coupling approaches for biosignal analysis and thus contribute in their own way to detailed information obtained, and thereby contribute to improved diagnostics/therapy. The main findings of this thesis revealed significantly weaker non-linear central-cardiovascular and central-cardiorespiratory coupling pathways, and significantly stronger linear central information flow in the direction of the cardiac- and vascular system, and a significantly stronger linear respiratory information transfer towards the central nervous system in schizophrenia in comparison to healthy participants. This thesis provides an enhanced understanding of the interrelationship of central and autonomic regulatory mechanisms in schizophrenia. The detailed findings on how variously-pronounced, central-autonomic-network pathways are associated with paranoid schizophrenia may enable a better understanding on how central activation and autonomic responses and/or activation are connected in physiology networks under pathophysiological conditions

Joint symbolic dynamics for the assessment of cardiovascular and cardiorespiratory interactions

Beat-to-beat variations in heart period provide information on cardiovascular control and are closely linked to variations in arterial pressure and respiration. Joint symbolic analysis of heart period, systolic arterial pressure and respiration allows for a simple description of their shared short-term dynamics that are governed by cardiac baroreflex control and cardiorespiratory coupling. In this review, we discuss methodology and research applications. Studies suggest that analysis of joint symbolic dynamics provides a powerful tool for identifying physiological and pathophysiological changes in cardiovascular and cardiorespiratory control.Mathias Baumert, Michal Javorka and Muammar Kabi

Characterization and interpretation of cardiovascular and cardiorespiratory dynamics in cardiomyopathy patients

Aplicat embargament des de la data de defensa fins el dia 20/5/2022The main objective of this thesis was to study the variability of the cardiac, respiratory and vascular systems through electrocardiographic (ECG), respiratory flow (FLW) and blood pressure (BP) signals, in patients with idiopathic (IDC), dilated (DCM), or ischemic (ICM) disease. The aim of this work was to introduce new indices that could contribute to characterizing these diseases. With these new indices, we propose methods to classify cardiomyopathy patients (CMP) according to their cardiovascular risk or etiology. In addition, a new tool was proposed to reconstruct artifacts in biomedical signals. From the ECG, BP and FLW signals, different data series were extracted: beat to beat intervals (BBI - ECG), systolic and diastolic blood pressure (SBP and DBP - BP), and breathing duration (TT - FLW). -Firstly, we propose a novel artifact reconstruction method applied to biomedical signals. The reconstruction process makes use of information from neighboring events while maintaining the dynamics of the original signal. The method is based on detecting the cycles and artifacts, identifying the number of cycles to reconstruct, and predicting the cycles used to replace the artifact segments. The reconstruction results showed that most of the artifacts were correctly detected, and physiological cycles were incorrectly detected as artifacts in fewer than 1% of the cases. The second part is related to the cardiac death risk stratification of patients based on their left ventricular ejection (LVEF), using the Poincaré plot analysis, and classified as low (LVEF > 35%) or high (LVEF = 35%) risk. The BBI, SBP, and IT series of 46 CMP patients were applied. The linear discriminant analysis and support vector machines (SVM) classification methods were used. When comparing low risk vs high risk, an accuracy of 98 12% was obtained. Our results suggest that a dysfunction in the vagal activity could prevent the body from correctly maintaining circulatory homeostasis Next, we studied cardio-vascular couplings based on heart rate (HRV) and blood pressure (BPV) variability analyses in order to introduce new indices for noninvasive risk stratification in IDC patients. The ECG and BP signals of 91 IDC patients, and 49 healthy subjects were used. The patients were stratified by their sudden cardiac death risk as: high risk (IDCHR), when after two years the subject either died or suffered complications, or low risk (IDCLR) otherwise. Several indices were extracted from the BBI and SBP, and analyzed using the segmented Poincaré plot analysis, the high-resolution joint symbolic dynamics, and the normalized short time partial directed coherence methods. SVM models were built to classify these patients based on their sudden cardiac death risk. The SVM IDCLR vs IDCHR model achieved 98 9% accuracy with an area under the curve (AUC) of 0.96. Our results suggest that IDCHR patients have decreased HRV and increased BPV compared to both the IDCLR patients and the control subjects, suggesting a decrease in their vagal activity and the compensation of sympathetic activity. Lastly, we analyzed the cardiorespiratory interaction associated with the systems related to ICM and DCM disease. We propose an analysis based on vascular activity as the input and output of the baroreflex response. The aim was to analyze the suitability of cardiorespiratory and vascular interactions for the classification of ICM and DCM patients. We studied 41 CMP patients and 39 healthy subjects. Three new sub-spaces were defined: 'up' for increasing values, 'down' for decreasing values, and 'no change' otherwise, and a three-dimensional representation was created for each sub-space that was characterized statistically and morphologically. The resulting indices were used to classify the patients by their etiology through SVM models achieving 92.7% accuracy for ICM vs DCM patients comparison. The results reflected a more pronounced deterioration of the autonomous regulation in DCM patients.El objetivo de esta tesis fue estudiar la variabilidad de los sistemas cardíaco, respiratorio y vascular a través de señales electrocardiográficas (ECG), de flujo respiratorio (FLW) y de presión arterial (BP), en pacientes con cardiopatía idiopática (IDC). dilatada (DCM) o isquémica (ICM). El objetivo de este trabajo fue introducir nuevos indices que contribuyan a caracterizar estas enfermedades. Proponemos métodos para clasificar pacientes con cardiomiopatía (CMP) de acuerdo con su riesgo cardiovascular o etiología. Además, se propuso una nueva herramienta para reconstruir artefactos en señales biomédicas. De las señales de ECG, BP y FLW, se extrajeron diferentes series temporales: intervalos latido-a-latido (BBI - ECG), presión arterial sistólica y diastólica (SBP y DBP - BP) y la duración de la respiración (TT - FLW). En primer lugar, proponemos un método de reconstrucción de artefactos aplicado a señales biomédicas. El proceso de reconstrucción usa la información de eventos vecinos manteniendo la dinámica de la señal. El método se basa en detectar ciclos y artefactos, en identificar el número de ciclos a reconstruir y en predecir los ciclos utilizados para reemplazar los artefactos. La mayoría de los artefactos probados fueron detectados y reconstruidos correctamente y los ciclos fisiológicos fueron detectados incorrectamente como artefactos en menos del 1% de los casos, La segunda parte está relacionada con la estratificación de riesgo de muerte cardiovascular en función de la fracción de eyección ventricular izquierda (FEVI), mediante el análisis de Poincaré, en bajo (FEVI > 35%) y alto riesgo (FEVI 5 35%). Se utilizaron las series BBI, SBP y TT de 46 pacientes con CMP. Se utilizaron para la clasificación el análisis discriminante lineal y las máquinas de soporte vectorial (SVM). Al comparar los pacientes de bajo y alto riesgo, se obtuvo una exactitud del 98%. Los resultados sugieren la disfunción de la actividad vagal en pacientes de alto riesgo. A continuación, estudiamos los acoplamientos cardiovasculares basados en el análisis de la variabilidad de la frecuencia cardiaca (HRV) y la presión arterial (BPV) para introducir nuevos índices de estratificación de riesgo en pacientes con IDC. Se utilizaron las señales de ECG y BP de 91 pacientes con IDC y 49 sujetos sanos. Los pacientes fueron estratificados por su riesgo cardíaco como: alto riesgo (IDCHR), cuando después de dos años el sujeto murió, o bajo riesgo (IDCLR) en otro caso. Se extrajeron indices utilizando el análisis de Poincaré segmentado, la dinámica simbólica articulada de alta resolución y la coherencia parcial dirigida a corto plazo normalizada. Se construyeron modelos SVM para clasificar a estos pacientes en función de su riesgo cardiovascular. El modelo IDCLR vs IDCHR logró una exactitud del 98% con un área bajo la curva de 0.96. Los resultados sugieren que los pacientes IDCHR tienen sus HRV y BPV disminuidos en comparación con los pacientes IDCLR, lo que sugiere una disminución en su actividad vagal y la compensación de la actividad simpática. Finalmente, analizamos la interacción cardiorrespiratoria asociada con los sistemas relacionados con ICM y DCM. Proponemos un análisis basado en la actividad vascular como entrada y salida de la respuesta baroreflectora. El objetivo fue analizar la capacidad de las interacciones cardiorrespiratorias y vasculares para la clasificación de pacientes con ICM y DCM. Estudiamos 41 pacientes con CMP y 39 sujetos sanos. Se definieron tres sub-espacios: 'up' para valores crecientes, 'down' para los decrecientes, y 'no-change' en otro caso, y se creó una representación tridimensional que se caracterizó estadística y morfológicamente. Los indices resultantes se usaron para clasificar a los pacientes por su etiología con modelos SVM que lograron una exactitud de 92% cuando los pacientes ICM y DCM fueron comparados. Los resultados reflejaron un deterioro más pronunciado de la regulación autónoma en pacientes con DCM.Postprint (published version

Association between autonomic control indexes and mortality in subjects admitted to intensive care unit

This study checks whether autonomic markers derived from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP) and from their interactions with spontaneous or mechanical respiration (R) are associated with mortality in patients admitted to intensive care unit (ICU). Three-hundred consecutive HP, SAP and R values were recorded during the first day in ICU in 123 patients. Population was divided into survivors (SURVs, n = 83) and non-survivors (NonSURVs, n = 40) according to the outcome. SURVs and NonSURVs were aged-and gender-matched. All subjects underwent modified head-up tilt (MHUT) by tilting the bed back rest segment to 60 degrees. Autonomic control indexes were computed using time-domain, spectral, cross-spectral, complexity, symbolic and causality techniques via univariate, bivariate and conditional approaches. SAP indexes derived from time-domain, model-free complexity and symbolic approaches were associated with the endpoint, while none of HP variability markers was. The association was more powerful during MHUT. Linear cross-spectral and causality indexes were useless to separate SURVs from NonSURVs, while nonlinear bivariate symbolic markers were successful. When indexes were combined with clinical scores, only SAP variance provided complementary information. Cardiovascular control variability indexes, especially when derived after an autonomic challenge such as MHUT, can improve mortality risk stratification in ICU

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 349)

This bibliography lists 149 reports, articles and other documents introduced into the NASA Scientific and Technical Information System during April, 1991. Subject coverage includes: aerospace medicine and psychology, life support systems and controlled environments, safety equipment, exobiology and extraterrestrial life, and flight crew behavior and performance

Instantaneous Transfer Entropy for the Study of Cardiovascular and Cardio-Respiratory Nonstationary Dynamics

Objective: Measures of Transfer Entropy (TE) quantify the direction and strength of coupling between two complex systems. Standard approaches assume stationarity of the observations, and therefore are unable to track time-varying changes in nonlinear information transfer with high temporal resolution. In this study, we aim to define and validate novel instantaneous measures of transfer entropy to provide an im- proved assessment of complex non-stationary cardio-respiratory interactions

Categorizing the Role of Respiration in Cardiovascular and Cerebrovascular Variability Interactions

Objective: Respiration disturbs cardiovascular and cerebrovascular controls but its role is not fully elucidated. Methods: Respiration can be classified as a confounder if its observation reduces the strength of the causal relationship from source to target. Respiration is a suppressor if the opposite situation holds. We prove that a confounding/suppression (C/S) test can be accomplished by evaluating the sign of net redundancy/synergy balance in the predictability framework based on multivariate autoregressive modelling. In addition, we suggest that, under the hypothesis of Gaussian processes, the C/S test can be given in the transfer entropy decomposition framework as well. Experimental protocols: We applied the C/S test to variability series of respiratory movements, heart period, systolic arterial pressure, mean arterial pressure, and mean cerebral blood flow recorded in 17 pathological individuals (age: 648 yrs; 17 males) before and after induction of propofol-based general anesthesia prior to coronary artery bypass grafting, and in 13 healthy subjects (age: 278 yrs; 5 males) at rest in supine position and during head-up tilt with a table inclination of 60. Results: Respiration behaved systematically as a confounder for cardiovascular and cerebrovascular controls. In addition, its role was affected by propofol-based general anesthesia but not by a postural stimulus of limited intensity. Conclusion: The C/S test can be fruitfully exploited to categorize the role of respiration over causal variability interactions. Significance: The application of the C/S test could favor the comprehension of the role of respiration in cardiovascular and cerebrovascular regulations

The Phrenic Component of Acute Schizophrenia – A Name and Its Physiological Reality

Decreased heart rate variability (HRV) was shown for unmedicated patients with schizophrenia and their first-degree relatives, implying genetic associations. This is known to be an important risk factor for increased cardiac mortality in other diseases. The interaction of cardio-respiratory function and respiratory physiology has never been investigated in the disease although it might be closely related to the pattern of autonomic dysfunction. We hypothesized that increased breathing rates and reduced cardio-respiratory coupling in patients with acute schizophrenia would be associated with low vagal function. We assessed variability of breathing rates and depth, HRV and cardio-respiratory coupling in patients, their first-degree relatives and controls at rest. Control subjects were investigated a second time by means of a stress task to identify stress-related changes of cardio-respiratory function. A total of 73 subjects were investigated, consisting of 23 unmedicated patients, 20 healthy, first-degree relatives and 30 control subjects matched for age, gender, smoking and physical fitness. The LifeShirt®, a multi-function ambulatory device, was used for data recording (30 minutes). Patients breathe significantly faster (p<.001) and shallower (p<.001) than controls most pronouncedly during exhalation. Patients' breathing is characterized by a significantly increased amount of middle- (p<.001), high- (p<.001), and very high frequency fluctuations (p<.001). These measures correlated positively with positive symptoms as assessed by the PANSS scale (e.g., middle frequency: r = 521; p<.01). Cardio-respiratory coupling was reduced in patients only, while HRV was decreased in patients and healthy relatives in comparison to controls. Respiratory alterations might reflect arousal in acutely ill patients, which is supported by comparable physiological changes in healthy subjects during stress. Future research needs to further investigate these findings with respect to their physiological consequences for patients. These results are invaluable for researchers studying changes of biological signals prone to the influence of breathing rate and rhythm (e.g., functional imaging)

Aerospace Medicine and Biology: A continuing bibliography with indexes

This bibliography lists 253 reports, articles, and other documents introduced into the NASA scientific and technical information system in October 1975

Three-Dimensional Segmented Poincaré Plot Analyses SPPA3 Investigates Cardiovascular and Cardiorespiratory Couplings in Hypertensive Pregnancy Disorders

Hypertensive pregnancy disorders affect 6 to 8% of gestations representing the most common complication of pregnancy for both mother and fetus. The aim of this study was to introduce a new three-dimensional coupling analysis methods – the three-dimensional segmented Poincaré plot analyses (SPPA3) - to establish an effective approach for the detection of hypertensive pregnancy disorders and especially pre-eclampsia (PE). A cubic box model representing the three dimensional phase space is subdivided into 12x12x12 equal predefined cubelets according to the range of the standard deviations of each investigated signal. Additionally, we investigated the influence of rotating the cloud of points and the size of the cubelets (adapted or predefined). All single probabilities of occurring points in a specific cubelet related to the total number of points are calculated. From 10 healthy non-pregnant women, 66 healthy pregnant women and 56 hypertensive pregnant women suffering from chronic hypertension, pregnancy induced hypertension and PE 30 minutes of beat-to-beat intervals (BBI), respiration (RESP), non-invasive systolic (SBP) and diastolic blood pressure (DBP) were continuously recorded and analyzed. Non-rotated adapted SPPA3 seems to be the optimum method to discriminate between hypertensive pregnancy disorders and PE concerning coupling analysis of 2 or 3 different systems (BBI, DBP, RESP and BBI, SBP, DBP) reaching an accuracy of up to 82.9%. This could be increased to an accuracy of up to 91.2% applying multivariate analysis differentiating between all pregnant women and PE. In conclusion, SPPA3 could be a useful method for enhanced risk stratification in pregnant women