Cardiovascular control in women with fibromyalgia syndrome: Do causal methods provide nonredundant information compared with more traditional approaches?

The cardiovascular autonomic control and the baroreflex sensitivity (BRS) have been widely studied in FMS patients through the computation of linear indices of spontaneous heart period (HP) and systolic arterial pressure (SAP) variabilities. However, there are many methodological difficulties regarding the quantification of BRS by the traditional indices especially in relation to the issue of causality. This difficulty has been directly tackled via a model-based approach describing the closed loop HP-SAP interactions and the exogenous influences of respiration. Therefore, we aimed to assess if the BRS assessed by the model-based causal closed-loop approach during supine and active standing in patients with FMS could provide complementary information to those obtained by traditional indices based on time and frequency domains. The findings of this study revealed that, although the traditional methods to quantify BRS did not show any significant differences between groups, the causality analysis applied to the HP, SAP and respiratory series, through the model based closed loop approach, detected lower BRS in supine position as well as a blunted response to the orthostatic stimulus in patients with FMS compared to healthy control subjects. Also, the strength of the causal relation from SAP to HP (i.e., along the cardiac baroreflex) increased during the active standing only in the control subjects. The model-based closed-loop approach proved to provide important complementary information about the cardiovascular autonomic control in patients with FMS

Assessment of Cardiorespiratory Interactions During Spontaneous and Controlled Breathing: Linear Parametric Analysis

In this work, we perform a linear parametric analysis of cardiorespiratory interactions in bivariate time series of heart period (HP) and respiration (RESP) measured in 19 healthy subjects during spontaneous breathing and controlled breathing at varying breathing frequency. The analysis is carried out computing measures of the total and causal interaction between HP and RESP variability in both time and frequency domains (low- and high-frequency, LF and HF). Results highlight strong cardiorespiratory interactions in the time domain and within the HF band that are not affected by the paced breathing condition. Interactions in the LF band are weaker and prevalent along the direction from HP to RESP, but result more influenced by the shift from spontaneous to controlled respiration

Assessment of Cardiorespiratory Interactions During Spontaneous and Controlled Breathing: Non-linear Model-free Analysis

In this work, nonlinear model-free methods for bivariate time series analysis have been applied to study cardiorespiratory interactions. Specifically, entropy-based (i.e. Transfer Entropy and Cross Entropy) and Convergent Cross Mapping asymmetric coupling measures have been computed on heart rate and breathing time series extracted from electrocardiographic (ECG) and respiratory signals acquired on 19 young healthy subjects during an experimental protocol including spontaneous and controlled breathing conditions. Results evidence a bidirectional nature of cardiorespiratory interactions, and highlight clear similarities and differences among the three considered measures

Multivariate and multiscale complexity of long-range correlated cardiovascular and respiratory variability series

Assessing the dynamical complexity of biological time series represents an important topic with potential applications ranging from the characterization of physiological states and pathological conditions to the calculation of diagnostic parameters. In particular, cardiovascular time series exhibit a variability produced by different physiological control mechanisms coupled with each other, which take into account several variables and operate across multiple time scales that result in the coexistence of short term dynamics and long-range correlations. The most widely employed technique to evaluate the dynamical complexity of a time series at different time scales, the so-called multiscale entropy (MSE), has been proven to be unsuitable in the presence of short multivariate time series to be analyzed at long time scales. This work aims at overcoming these issues via the introduction of a new method for the assessment of the multiscale complexity of multivariate time series. The method first exploits vector autoregressive fractionally integrated (VARFI) models to yield a linear parametric representation of vector stochastic processes characterized by short- and long-range correlations. Then, it provides an analytical formulation, within the theory of state-space models, of how the VARFI parameters change when the processes are observed across multiple time scales, which is finally exploited to derive MSE measures relevant to the overall multivariate process or to one constituent scalar process. The proposed approach is applied on cardiovascular and respiratory time series to assess the complexity of the heart period, systolic arterial pressure and respiration variability measured in a group of healthy subjects during conditions of postural and mental stress. Our results document that the proposed methodology can detect physiologically meaningful multiscale patterns of complexity documented previously, but can also capture significant variations in complexity which cannot be observed using standard methods that do not take into account long-range correlations.publishe

Concomitant evaluation of cardiovascular and cerebrovascular controls via Geweke spectral causality to assess the propensity to postural syncope

The evaluation of propensity to postural syncope necessitates the concomitant characterization of the cardiovascular and cerebrovascular controls and a method capable of disentangling closed loop relationships and decomposing causal links in the frequency domain. We applied Geweke spectral causality (GSC) to assess cardiovascular control from heart period and systolic arterial pressure variability and cerebrovascular regulation from mean arterial pressure and mean cerebral blood velocity variability in 13 control subjects and 13 individuals prone to develop orthostatic syncope. Analysis was made at rest in supine position and during head-up tilt at 60°, well before observing presyncope signs. Two different linear model structures were compared, namely bivariate autoregressive and bivariate dynamic adjustment classes. We found that (i) GSC markers did not depend on the model structure; (ii) the concomitant assessment of cardiovascular and cerebrovascular controls was useful for a deeper comprehension of postural disturbances; (iii) orthostatic syncope appeared to be favored by the loss of a coordinated behavior between the baroreflex feedback and mechanical feedforward pathway in the frequency band typical of the baroreflex functioning during the postural challenge, and by a weak cerebral autoregulation as revealed by the increased strength of the pressure-to-flow link in the respiratory band. GSC applied to spontaneous cardiovascular and cerebrovascular oscillations is a promising tool for describing and monitoring disturbances associated with posture modification

A New Framework for the Time- and Frequency-Domain Assessment of High-Order Interactions in Networks of Random Processes

While the standard network description of complex systems is based on quantifying the link between pairs of system units, higher-order interactions (HOIs) involving three or more units often play a major role in governing the collective network behavior. This work introduces a new approach to quantify pairwise and HOIs for multivariate rhythmic processes interacting across multiple time scales. We define the so-called O-information rate (OIR) as a new metric to assess HOIs for multivariate time series, and present a framework to decompose the OIR into measures quantifying Granger-causal and instantaneous influences, as well as to expand all measures in the frequency domain. The framework exploits the spectral representation of vector autoregressive and state space models to assess the synergistic and redundant interaction among groups of processes, both in specific bands of interest and in the time domain after whole-band integration. Validation of the framework on simulated networks illustrates how the spectral OIR can highlight redundant and synergistic HOIs emerging at specific frequencies, which cannot be detected using time-domain measures. The applications to physiological networks described by heart period, arterial pressure and respiration variability measured in healthy subjects during a protocol of paced breathing, and to brain networks described by electrocorticographic signals acquired in an animal experiment during anesthesia, document the capability of our approach to identify informational circuits relevant to well-defined cardiovascular oscillations and brain rhythms and related to specific physiological mechanisms involving autonomic control and altered consciousness. The proposed framework allows a hierarchically-organized evaluation of timeand frequency-domain interactions in dynamic networks mapped by multivariate time series, and its high flexibility and scalability make it suitable for the investigation of networks beyond pairwise interactions in neuroscience, physiology and many other fields

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

Multivariate correlation measures reveal structure and strength of brain–body physiological networks at rest and during mental stress

In this work, we extend to the multivariate case the classical correlation analysis used in the field of network physiology to probe dynamic interactions between organ systems in the human body. To this end, we define different correlation-based measures of the multivariate interaction (MI) within and between the brain and body subnetworks of the human physiological network, represented, respectively, by the time series of delta, theta, alpha, and beta electroencephalographic (EEG) wave amplitudes, and of heart rate, respiration amplitude, and pulse arrival time (PAT) variability (eta, rho, pi). MI is computed: (i) considering all variables in the two subnetworks to evaluate overall brain-body interactions; (ii) focusing on a single target variable and dissecting its global interaction with all other variables into contributions arising from the same subnetwork and from the other subnetwork; and (iii) considering two variables conditioned to all the others to infer the network topology. The framework is applied to the time series measured from the EEG, electrocardiographic (ECG), respiration, and blood volume pulse (BVP) signals recorded synchronously via wearable sensors in a group of healthy subjects monitored at rest and during mental arithmetic and sustained attention tasks. We find that the human physiological network is highly connected, with predominance of the links internal of each subnetwork (mainly eta-rho and delta-theta, theta-alpha, alpha-beta), but also statistically significant interactions between the two subnetworks (mainly eta-beta and eta-delta). MI values are often spatially heterogeneous across the scalp and are modulated by the physiological state, as indicated by the decrease of cardiorespiratory interactions during sustained attention and by the increase of brain-heart interactions and of brain-brain interactions at the frontal scalp regions during mental arithmetic. These findings illustrate the complex and multi-faceted structure of interactions manifested within and between different physiological systems and subsystems across different levels of mental stress

Non-linear Heart Rate and Blood Pressure Interaction in Response to Lower-Body Negative Pressure

Early detection of hemorrhage remains an open problem. In this regard, blood pressure has been an ineffective measure of blood loss due to numerous compensatory mechanisms sustaining arterial blood pressure homeostasis. Here, we investigate the feasibility of causality detection in the heart rate and blood pressure interaction, a closed-loop control system, for early detection of hemorrhage. The hemorrhage was simulated via graded lower-body negative pressure (LBNP) from 0 to -40 mmHg. The research hypothesis was that a significant elevation of causal control in the direction of blood pressure to heart rate (i.e., baroreflex response) is an early indicator of central hypovolemia. Five minutes of continuous blood pressure and electrocardiogram (ECG) signals were acquired simultaneously from young, healthy participants (27 ± 1 years, N = 27) during each LBNP stage, from which heart rate (represented by RR interval), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were derived. The heart rate and blood pressure causal interaction (RR SBP and RR MAP) was studied during the last 3 min of each LBNP stage. At supine rest, the non-baroreflex arm (RR SBP and RR MAP) showed a significantly (p \u3c 0.001) higher causal drive toward blood pressure regulation compared to the baroreflex arm (SBP RR and MAP RR). In response to moderate category hemorrhage (-30 mmHg LBNP), no change was observed in the traditional marker of blood loss i.e., pulse pressure (p = 0.10) along with the RR SBP (p = 0.76), RR MAP (p = 0.60), and SBP RR (p = 0.07) causality compared to the resting stage. Contrarily, a significant elevation in the MAP RR (p = 0.004) causality was observed. In accordance with our hypothesis, the outcomes of the research underscored the potential of compensatory baroreflex arm (MAP RR) of the heart rate and blood pressure interaction toward differentiating a simulated moderate category hemorrhage from the resting stage. Therefore, monitoring baroreflex causality can have a clinical utility in making triage decisions to impede hemorrhage progression

Disentangling cardiovascular control mechanisms during head-down tilt via joint transfer entropy and self-entropy decompositions

A full decomposition of the predictive entropy (PE) of the spontaneous variations of the heart period (HP) given systolic arterial pressure (SAP) and respiration (R) is proposed. The PE of HP is decomposed into the joint transfer entropy (JTE) from SAP and R to HP and self-entropy (SE) of HP. The SE is the sum of three terms quantifying the synergistic/redundant contributions of HP and SAP, when taken individually and jointly, to SE and one term conditioned on HP and SAP denoted as the conditional SE (CSE) of HP given SAP and R. The JTE from SAP and R to HP is the sum of two terms attributable to SAP or R plus an extra term describing the redundant/synergistic contribution to the JTE. All quantities were computed during cardiopulmonary loading induced by -25\uc2\ub0 head-down tilt (HDT) via a multivariate linear regression approach. We found that: (i) the PE of HP decreases during HDT; (ii) the decrease of PE is attributable to a lessening of SE of HP, while the JTE from SAP and R to HP remains constant; (iii) the SE of HP is dominant over the JTE from SAP and R to HP and the CSE of HP given SAP and R is prevailing over the SE of HP due to SAP and R both in supine position and during HDT; (iv) all terms of the decompositions of JTE from SAP and R to HP and SE of HP due to SAP and R were not affected by HDT; (v) the decrease of the SE of HP during HDT was attributed to the reduction of the CSE of HP given SAP and R; (vi) redundancy of SAP and R is prevailing over synergy in the information transferred into HP both in supine position and during HDT, while in the HP information storage synergy and redundancy are more balanced. The approach suggests that the larger complexity of the cardiac control during HDT is unrelated to the baroreflex control and cardiopulmonary reflexes and may be related to central commands and/or modifications of the dynamical properties of the sinus node